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Search Results (267)

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Keywords = cancer antigen 72-4 (CA72-4)

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14 pages, 3666 KiB  
Article
A Sensitive Sandwich-Type Electrochemical Immunosensor for Carbohydrate Antigen 19-9 Based on Covalent Organic Frameworks
by Ting Wu, Rongfang Chen, Yaqin Duan, Longfei Miao, Yongmei Zhu and Li Wang
Biosensors 2025, 15(8), 492; https://doi.org/10.3390/bios15080492 - 1 Aug 2025
Viewed by 210
Abstract
Since carbohydrate antigen 19-9 (CA 19-9) is a significant biomarker for the clinical diagnosis and treatment of pancreatic cancer, a sensitive sandwich-type immunosensor was proposed with an epoxy functionalized covalent organic framework (EP-COFTTA-DHTA) as the antibody carrier and an electroactive COF [...] Read more.
Since carbohydrate antigen 19-9 (CA 19-9) is a significant biomarker for the clinical diagnosis and treatment of pancreatic cancer, a sensitive sandwich-type immunosensor was proposed with an epoxy functionalized covalent organic framework (EP-COFTTA-DHTA) as the antibody carrier and an electroactive COFTTA-2,6-NA(OH)2 as the signal amplification probe for the sensitive detection of CA 19-9. The flexible covalent linkage between the epoxy-functionalized EP-COFTTA-DHTA and the antibodies was employed to improve the dynamics of the antigen–antibody interaction significantly. Meanwhile, AuNPs@COFTTA-2,6-NA(OH)2 with abundant electroactive sites enhanced the current response of the immunoreaction significantly. After optimizing the incubation time and concentration of the antibody, CA 19-9 was quantitatively detected by differential pulse voltammetry (DPV) based on the sensitive sandwich-type immunosensor with a low detection limit of 0.0003 U/mL and a wide linear range of 0.0009–100 U/mL. The electrochemical immunosensor exhibits high specificity, stability and repeatability, and it provides a feasible and efficient method for the pathologic analysis and treatment of tumor markers. Full article
(This article belongs to the Special Issue Advances in Biosensors Based on Framework Materials)
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16 pages, 663 KiB  
Article
A Disintegrin and Metalloprotease 15 (ADAM15) as a Potential Predictor of Distant Metastasis in Colorectal Cancer (CRC)
by Adrianna Romanowicz, Marta Łukaszewicz-Zając, Barbara Choromańska, Sara Pączek, Hady Razak Hady, Piotr Myśliwiec, Jacek Jamiołkowski, Piotr Stępniewski, Leszek Kozłowski and Barbara Mroczko
J. Clin. Med. 2025, 14(14), 5082; https://doi.org/10.3390/jcm14145082 - 17 Jul 2025
Viewed by 300
Abstract
Background: The pro-tumorigenic role of a disintegrin and metalloprotease 15 (ADAM15) is supported by its modified expression in primary tumors and ability to promote tumor growth in colorectal cancer (CRC). Cancer cell-derived ADAM15 promotes the progression of this malignancy by modulating the tumor [...] Read more.
Background: The pro-tumorigenic role of a disintegrin and metalloprotease 15 (ADAM15) is supported by its modified expression in primary tumors and ability to promote tumor growth in colorectal cancer (CRC). Cancer cell-derived ADAM15 promotes the progression of this malignancy by modulating the tumor microenvironment. However, according to our knowledge, this study is the first to assess serum ADAM15 concentrations in CRC patients in comparison to classical tumor markers—carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9)—and a marker of the inflammatory process, C-reactive protein (CRP). The aim was to evaluate whether circulating serum ADAM15 might be a candidate biomarker for CRC diagnosis and progression. Methods: The study included 110 CRC patients and 54 healthy volunteers. Serum concentrations of ADAM15, CEA, and CA19-9 were measured using immunoenzyme assays, while CRP levels were assessed by the turbidimetric method. Diagnostic characteristics of all tested proteins were calculated. Results: Serum ADAM15 and classical tumor marker (CEA and CA19) levels were higher in CRC patients than in healthy subjects. However, a significant difference was observed only for CEA (p < 0.001). ADAM15 concentrations were significantly higher in CRC patients with distant metastases compared to those without metastases (p = 0.043). The highest diagnostic sensitivity (89%) was achieved by combined analysis of ADAM15 and CRP levels. Conclusions: These findings suggest a significant role of ADAM15 in CRC pathogenesis, indicating the usefulness of this protein in the prediction of distant metastases. Measurement of serum ADAM15, especially in combination with classical tumor markers (CEA) and inflammation markers (CRP), may improve the diagnosis of patients with CRC. Full article
(This article belongs to the Section General Surgery)
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15 pages, 979 KiB  
Article
Unveiling the Diagnostic Significance of Calprotectin in Serous Ovarian Carcinoma
by Alkis Matsas, Eleni Stamoula, Konstantinos Kontzoglou, Makarios Eleftheriades, Sophia Tsokkou, Panagiotis Christopoulos, Theodoros Panoskaltsis, Eleni Polydorou, Ioannis Sotiropoulos, Theodore Troupis and Dimitrios C. Iliopoulos
Life 2025, 15(7), 1080; https://doi.org/10.3390/life15071080 - 8 Jul 2025
Viewed by 604
Abstract
Introduction: Ovarian cancer (OC) is one of the most common gynecologic malignancies and has the highest mortality rate among them. OC has a multifactorial pathogenesis and is characterized by silent onset, progression, and late-stage detection. Therefore, accurate and early detection is of [...] Read more.
Introduction: Ovarian cancer (OC) is one of the most common gynecologic malignancies and has the highest mortality rate among them. OC has a multifactorial pathogenesis and is characterized by silent onset, progression, and late-stage detection. Therefore, accurate and early detection is of great importance in order to improve survival rates. Emerging evidence reveals that tumor markers are valuable diagnostic and monitoring tools. In this study, we evaluated the aforementioned potential of three markers CA-125, CA 15-3, and serum Calprotectin. CA-125 is a protein that is found elevated in cases of ovarian, breast, and lung cancer. Cancer Antigen 15-3 (CA 15-3) is a protein detected in high levels in women with breast cancer and ovarian cancer and it is significantly elevated in patients with metastasis and recurrence of OC. Calprotectin is a protein released from activated neutrophils, related to inflammatory conditions and can be a potential immune-mediated marker in OC. Purpose: The purpose of this study was to explore the significance of serum calprotectin, CA-125, and CA 15-3 in women diagnosed with serous OC. Methodology: Thirty-eight (38) women with diagnosed OC were included in this research as the study group and twenty-seven (27) healthy women with no history or current diagnosis of OC were included in the control group. Women in both groups shared similar past histories to avoid any other parameters interfering with the study. Our study group was further subdivided into early stage and advanced stage patients. Blood samples were collected from all women of both groups and were examined using ELISA kits to evaluate the levels of the above markers. Results: When comparing patients versus control patients, those with OC exhibited higher levels of Calprotectin compared to healthy individuals. Additionally, Calprotectin showed a statistically significant elevation between the control group and advanced patients. CA-125 remains the current standard of care biomarker exhibiting 90% sensitivity, whereas sensitivities in Calprotectin and CA 15-3 were 60% and 50%, respectively. Conclusions: Serum CA-125 remains the single most valuable biomarker for ovarian cancer, having the highest statistical significance, correlation with disease stage, detecting both early or advanced patients, and sensitivity of 90%. It appears to be a promising inflammatory biomarker in the early diagnosis of ovarian cancer, showing an elevation in patients, while CA 15-3 provides moderate complementary information and exhibits inferior sensitivity when compared to both CA-125 and Calprotectin. The latter appears to be a promising marker and further studies could show if its addition to established protocols could improve early detection, disease progression, or risk stratification. Calprotectin enhances the detection range for ovarian cancer when used alongside CA-125, while this combined approach detected a greater proportion of patients than CA-125 alone, indicating improved diagnostic potential. Full article
(This article belongs to the Section Medical Research)
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10 pages, 2482 KiB  
Article
Trajectories of Cancer Antigen 125 (CA125) Within 3 and 6 Months After the Initiation of Chemotherapy Treatment for Advanced Ovarian Cancer and Clinical Outcomes: A Secondary Analysis of Data from a Phase III Clinical Trial
by Chang Yin, Josee-Lyne Ethier, Mark S. Carey, Dongsheng Tu and Xueying Zheng
Curr. Oncol. 2025, 32(7), 390; https://doi.org/10.3390/curroncol32070390 - 7 Jul 2025
Viewed by 485
Abstract
Background: A single measurement or a summary of a limited number of measurements of CA125 was considered in the prediction of clinical outcomes for patients with ovarian cancer. We aimed to identify the classes of patients with advanced ovarian cancer based on their [...] Read more.
Background: A single measurement or a summary of a limited number of measurements of CA125 was considered in the prediction of clinical outcomes for patients with ovarian cancer. We aimed to identify the classes of patients with advanced ovarian cancer based on their CA125 trajectory and to investigate the heterogeneity of clinical outcomes among the patients in the different classes. Methods: CA125 trajectory classes were identified by latent-class mixed models based on values collected within 3 and 6 months post-treatment for 819 women with advanced ovarian cancer enrolled in a randomized trial. Results: Based on their CA125 values during the first 6 months of treatment, the patients with low CA125 levels at baseline that remained low during treatment had the best clinical outcome (a median survival of 83 months and a progression-free survival of 34 months). In contrast, the patients with high CA125 values at baseline with a modest decrease during treatment had the highest risk of death and progression (hazard ratio [95% confidence interval]: 4.83 [3.56, 6.54] for overall survival and 5.15 [3.87, 6.87] for progression-free survival). Conclusions: Longitudinal trajectories of CA125 may provide more direct information for the prognoses of patients with advanced ovarian cancer undergoing chemotherapy treatment. Full article
(This article belongs to the Section Gynecologic Oncology)
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18 pages, 4103 KiB  
Article
Dual-Emitting Molecularly Imprinted Nanopolymers for the Detection of CA19-9
by Eduarda Rodrigues, Ana Xu, Rafael C. Castro, David S. M. Ribeiro, João L. M. Santos and Ana Margarida L. Piloto
Biomedicines 2025, 13(7), 1629; https://doi.org/10.3390/biomedicines13071629 - 3 Jul 2025
Viewed by 450
Abstract
Background/Objectives: Carbohydrate antigen 19-9 (CA19-9) is a clinically established biomarker primarily used for monitoring disease progression and recurrence in pancreatic and gastrointestinal cancers. Accurate and continuous quantification of CA19-9 in patient samples is critical for effective clinical management. This study aimed to develop [...] Read more.
Background/Objectives: Carbohydrate antigen 19-9 (CA19-9) is a clinically established biomarker primarily used for monitoring disease progression and recurrence in pancreatic and gastrointestinal cancers. Accurate and continuous quantification of CA19-9 in patient samples is critical for effective clinical management. This study aimed to develop dual-emitting molecularly imprinted nanopolymers (dual@nanoMIPs) for ratiometric and reliable detection of CA19-9 in serum. Methods: Dual-emitting nanoMIPs were synthesized via a one-step molecular imprinting process, incorporating both blue-emitting carbon dots (b-CDs) as internal reference fluorophores and yellow-emitting quantum dots (y-QDs) as responsive probes. The CA19-9 template was embedded into the polymer matrix to create specific recognition sites. Fluorescence measurements were carried out under 365 nm excitation in 1% human serum diluted in phosphate-buffered saline (PBS). Results: The dual@nanoMIPs exhibited a ratiometric fluorescence response upon CA19-9 binding, characterized by the emission quenching of the y-QDs at 575 nm, while the b-CDs emission remained stable at 467 nm. The fluorescence shift observed in the RGB coordinates from yellow to green in the concentration range of CA19-9 tested, improved quantification accuracy by compensating for matrix effects in serum. A linear detection range was achieved from 4.98 × 10−3 to 8.39 × 102 U mL−1 in serum samples, with high specificity and reproducibility. Conclusions: The dual@nanoMIPs developed in this work enable a stable, sensitive, and specific detection of CA19-9 in minimally processed serum, offering a promising tool for longitudinal monitoring of cancer patients. Its ratiometric fluorescence design enhances reliability, supporting clinical decision-making in the follow-up of pancreatic cancer. Full article
(This article belongs to the Special Issue Application of Biomedical Materials in Cancer Therapy)
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16 pages, 1241 KiB  
Article
Nutritional and Biochemical Outcomes After Total Versus Subtotal Gastrectomy: Insights into Early Postoperative Prognosis
by Fawzy Akad, Cristinel Ionel Stan, Florin Zugun-Eloae, Sorin Nicolae Peiu, Nada Akad, Dragos-Valentin Crauciuc, Marius Constantin Moraru, Cosmin Gabriel Popa, Liviu-Ciprian Gavril, Roxana-Florentina Sufaru, Cristina Preda and Veronica Mocanu
Nutrients 2025, 17(13), 2146; https://doi.org/10.3390/nu17132146 - 27 Jun 2025
Viewed by 485
Abstract
Gastric cancer remains a significant global health burden, with curative treatment relying on surgical resection, typically total or subtotal gastrectomy. However, the procedure frequently triggers acute metabolic and nutritional disturbances that may impact recovery. Objective: This prospective study aimed to investigate whether [...] Read more.
Gastric cancer remains a significant global health burden, with curative treatment relying on surgical resection, typically total or subtotal gastrectomy. However, the procedure frequently triggers acute metabolic and nutritional disturbances that may impact recovery. Objective: This prospective study aimed to investigate whether the type of gastrectomy (total vs. subtotal) influences early postoperative biochemical and hematological alterations, with particular attention to nutritional impact. Methods: A cohort of 295 patients (123 female, 172 male) who underwent gastrectomy for gastric cancer at the Institute of Oncology Iași (2023–2024) was evaluated. Laboratory parameters, including hemoglobin, hematocrit, lymphocyte and platelet counts, serum albumin, total protein, sodium, potassium, creatinine, and urea, were analyzed preoperatively and on postoperative day 14 using standard clinical methods. Results: Anemia was observed in over 90% of patients, irrespective of sex or procedure type. Electrolyte imbalances (notably hyponatremia and hypokalemia) and indicators of nutritional deficit (hypoalbuminemia, low creatinine) were highly prevalent, with a greater frequency among female patients. Total gastrectomy was associated with more severe biochemical and nutritional alterations compared to subtotal procedures. Conclusions: Total gastrectomy significantly exacerbates early postoperative metabolic and nutritional derangements. These findings reinforce the need for proactive, personalized postoperative nutritional and electrolyte management strategies to support recovery and reduce complication risks. Full article
(This article belongs to the Special Issue Diet, Nutrition, Supplements and Integrative Oncology in Cancer Care)
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13 pages, 1792 KiB  
Article
A High-Sensitivity, Bluetooth-Enabled PCB Biosensor for HER2 and CA15-3 Protein Detection in Saliva: A Rapid, Non-Invasive Approach to Breast Cancer Screening
by Hsiao-Hsuan Wan, Chao-Ching Chiang, Fan Ren, Cheng-Tse Tsai, Yu-Siang Chou, Chun-Wei Chiu, Yu-Te Liao, Dan Neal, Coy D. Heldermon, Mateus G. Rocha and Josephine F. Esquivel-Upshaw
Biosensors 2025, 15(6), 386; https://doi.org/10.3390/bios15060386 - 15 Jun 2025
Viewed by 931
Abstract
Breast cancer is a leading cause of cancer-related mortality worldwide, requiring efficient diagnostic tools for early detection and monitoring. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for breast cancer classification, typically assessed using immunohistochemistry (IHC). However, IHC requires invasive [...] Read more.
Breast cancer is a leading cause of cancer-related mortality worldwide, requiring efficient diagnostic tools for early detection and monitoring. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for breast cancer classification, typically assessed using immunohistochemistry (IHC). However, IHC requires invasive biopsies and time-intensive laboratory procedures. In this study, we present a biosensor integrated with a reusable printed circuit board (PCB) and functionalized glucose test strips designed for rapid and non-invasive HER2 detection in saliva. The biosensor achieved a limit of detection of 10−15 g/mL, 4 to 5 orders of magnitude more sensitive than the enzyme-linked immunosorbent assay (ELISA), with a sensitivity of 95/dec and a response time of 1 s. In addition to HER2, the biosensor also detects cancer antigen 15-3 (CA15-3), another clinically relevant breast cancer biomarker. The CA15-3 test demonstrated an equally low limit of detection, 10−15 g/mL, and a higher sensitivity, 190/dec, further validated using human saliva samples. Clinical validation using 29 saliva samples confirmed our biosensor’s ability to distinguish between healthy, in situ breast cancer, and invasive breast cancer patients. The system, which integrates a Bluetooth Low-Energy (BLE) module, enables remote monitoring, reduces hospital visits, and enhances accessibility for point-of-care and mobile screening applications. This ultra-sensitive, rapid, and portable biosensor can serve as a promising alternative for breast cancer detection and monitoring, particularly in rural and underserved communities. Full article
(This article belongs to the Special Issue Aptamer-Based Biosensors for Point-of-Care Diagnostics)
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18 pages, 1035 KiB  
Review
CA125 as a Potential Biomarker in Non-Malignant Serous Effusions: Diagnostic and Prognostic Considerations
by Lavinia Alice Bălăceanu, Cristiana Grigore, Ion Dina, Cristian-Dorin Gurău, Mara Mădălina Mihai and Beatrice Bălăceanu-Gurău
J. Clin. Med. 2025, 14(12), 4152; https://doi.org/10.3390/jcm14124152 - 11 Jun 2025
Viewed by 1167
Abstract
Background/Objectives: Carbohydrate antigen 125 (CA125) is a glycoprotein commonly overexpressed in epithelial ovarian cancer and widely recognized as a tumor marker. However, elevated CA125 levels are also observed in various non-malignant conditions, including diseases affecting mucosal surfaces, pleural or peritoneal effusions, cirrhosis (with [...] Read more.
Background/Objectives: Carbohydrate antigen 125 (CA125) is a glycoprotein commonly overexpressed in epithelial ovarian cancer and widely recognized as a tumor marker. However, elevated CA125 levels are also observed in various non-malignant conditions, including diseases affecting mucosal surfaces, pleural or peritoneal effusions, cirrhosis (with or without ascites), endometriosis, uterine fibroids, adenomyosis, pelvic inflammatory disease, and pregnancy. This review aims to explore the role of CA125 in non-malignant serous effusions, highlighting its diagnostic and prognostic potential beyond the realm of oncology. Methods: A comprehensive literature search was conducted across multiple databases and clinical trial registries. Eligible studies included full-text original research articles, reviews, and case reports published in English over the past 10 years. Inclusion criteria were limited to studies involving human subjects and focused on the role of CA125 in non-malignant serous effusions. Results: CA125 is produced by coelomic epithelial cells lining the ovary, pleura, pericardium, and peritoneum. Its serum concentration is not significantly influenced by age, body weight, or renal function, even in the advanced stages of the disease. In peritoneal conditions, CA125 is synthesized by mesothelial cells and serves as a potential marker of peritoneal involvement. The prevailing pathophysiological mechanism suggests that mechanical stretching of mesothelial cells due to ascitic pressure stimulates CA125 release. Similarly, in heart failure, mesothelial cells of the pericardium produce CA125, which correlates with congestion severity, supports risk stratification, and may inform diuretic therapy. Conclusions: While a threshold of 35 U/mL is established for malignancy, no standardized cutoff exists for CA125 in non-malignant conditions. The utility of CA125 measurement in peritoneal, pleural, or pericardial effusions—and cardiovascular diseases such as acute heart failure—for purposes of differential diagnosis, treatment guidance, or prognostication warrants further investigation through prospective clinical trials. Full article
(This article belongs to the Section Oncology)
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18 pages, 1252 KiB  
Review
Precision Oncology Framework Using Circulating Tumor Cells
by Fumihiko Kakizaki, Kyoichi Oshiro, Yuya Enoki, Kana Kawanishi, Norikazu Masuda, Hisatsugu Maekawa, Jun Matsubayashi, Masahiro Kawashima, Hiroyuki Miyoshi, Yukitoshi Takemura and Kazutaka Obama
Int. J. Mol. Sci. 2025, 26(12), 5539; https://doi.org/10.3390/ijms26125539 - 10 Jun 2025
Viewed by 1213
Abstract
Circulating tumor cells (CTCs) are multifaceted biomarkers with significant potential for precision oncology, offering opportunities to refine diagnoses and personalize treatments across various cancer types, including colorectal and breast cancer. CTC assays serve as reliable prognostic indicators, even during chemotherapy and/or molecularly targeted [...] Read more.
Circulating tumor cells (CTCs) are multifaceted biomarkers with significant potential for precision oncology, offering opportunities to refine diagnoses and personalize treatments across various cancer types, including colorectal and breast cancer. CTC assays serve as reliable prognostic indicators, even during chemotherapy and/or molecularly targeted therapies. Notably, CTCs exhibit heterogeneity that gradually develops during carcinogenesis and becomes more pronounced in advanced disease stages. These intra- and intertumoral heterogeneities pose challenges, particularly when drug-resistant clones emerge following therapy. The dynamic behavior of CTCs provides valuable insights into treatment response and prognosis. Extensive efforts have led to the development of technologies for effective CTC isolation, accelerating their clinical implementation. While both CTC and circulating tumor DNA (ctDNA) tests offer prognostic value, they reflect different aspects of tumor biology: CTC counts indicate tumor progression, while ctDNA levels correlate with tumor burden. The combined analysis is expected to yield complementary insights. CTC tests are feasible in general hospitals and may serve as tumor markers comparable to, or even superior to, conventional markers such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) for colorectal cancer, and CA15-3 for breast cancer. Early incorporation of CTC tests into routine blood panels appears to be a rational and promising approach. Full article
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14 pages, 3146 KiB  
Article
A High Performing Biomarker Signature for Detecting Early-Stage Pancreatic Ductal Adenocarcinoma in High-Risk Individuals
by Norma A. Palma, Aimee L. Lucas, Bryson W. Katona, Alcibiade Athanasiou, Natasha M. Kureshi, Lisa Ford, Thomas Keller, Stephen Weber, Ralph Schiess, Thomas King, Diane M. Simeone and Randall Brand
Cancers 2025, 17(11), 1866; https://doi.org/10.3390/cancers17111866 - 2 Jun 2025
Viewed by 1357
Abstract
Background/Objectives: Early detection of pancreatic cancer can improve patient survival, and blood-based biomarkers to aid in this are a significant need. The goal of this study was to develop and evaluate the performance of a 4- to 6-plex biomarker signature for detection of [...] Read more.
Background/Objectives: Early detection of pancreatic cancer can improve patient survival, and blood-based biomarkers to aid in this are a significant need. The goal of this study was to develop and evaluate the performance of a 4- to 6-plex biomarker signature for detection of early-stage pancreatic ductal adenocarcinoma (PDAC) that performs well in high-risk controls. Methods: Enzyme-linked immunosorbent assays were used to measure 10 previously identified serum protein biomarker candidates in Stage I and II PDAC cases (n = 128), high-risk controls (n = 465), and normal-risk controls (n = 30). Various combinations of biomarker candidates (models) were trained using machine learning and tested for robustness in differentiating cases from controls on the full cohort and in clinically relevant sub-types including those with diabetes, those ≥65 years of age, and low producers of carbohydrate antigen 19-9 (CA 19-9). Results: At 98% specificity, the top performing model, which was comprised of tissue inhibitor of metalloproteinase 1 (TIMP1), intracellular adhesion molecule 1 (ICAM1), thrombospondin 1 (THBS1), cathepsin D (CTSD), and CA 19-9, achieved 85% sensitivity in the full cohort and sensitivities of 91% in diabetics, 90% in ≥65 years of age, and 60% in low CA 19-9 producers. This model demonstrated significantly higher sensitivity in detecting PDAC in the full cohort and all sub-populations compared to CA 19-9 alone (p < 0.001). Conclusions: Our findings demonstrate the feasibility of a blood-based assay for detecting early-stage PDAC in high-risk individuals and key sub-populations, representing an important step towards improving diagnostic success for early-stage disease. Full article
(This article belongs to the Section Cancer Biomarkers)
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14 pages, 786 KiB  
Article
Synaptophysin-like-1: A Novel Serum Diagnostic Marker for Pancreatic Ductal Adenocarcinoma Screening, Early Diagnosis, and Prognosis Prediction
by Sefa Ergun, Taskin Avci, Seyma Dumur, Yasemin Pekmezci, Hafize Uzun, Uğurcan Sayılı, Yagmur Ozge Turac Kosem, Osman Simsek and Salih Pekmezci
J. Clin. Med. 2025, 14(11), 3719; https://doi.org/10.3390/jcm14113719 - 26 May 2025
Viewed by 488
Abstract
Background: The role and underlying mechanisms of synaptophysin-like-1 (SYPL1), a neuroendocrine-associated protein, in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study aims to assess the diagnostic potential of SYPL1 as a serum biomarker for both resectable PDAC (rPDAC) and metastatic PDAC (mPDAC) located [...] Read more.
Background: The role and underlying mechanisms of synaptophysin-like-1 (SYPL1), a neuroendocrine-associated protein, in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study aims to assess the diagnostic potential of SYPL1 as a serum biomarker for both resectable PDAC (rPDAC) and metastatic PDAC (mPDAC) located at the head of the pancreas. Additionally, the SYPL1 levels were monitored in PDAC patients who underwent surgical resection, with follow-up measurements taken 6 months postoperatively. Method: We analyzed serum SYPL1 in healthy controls (n = 67), rPDAC patients (n = 39), mPDAC patients (n = 22), and rPDAC patients (6-month postoperative) (n = 20) (due to factors such as relocation or death, 20 patients were included instead of 39 patients) by ELISA. Results: The SYPL-1 levels showed significant differences across the groups (controls: 7.43 ± 3.32, PC: 15.89 ± 2.00, mPDAC: 20.01 ± 4.03, p < 0.001). Both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were significantly greater in cancer groups compared to the healthy group. In patients who underwent surgical resection, the SYPL-1 levels showed a significant decrease 6 months after surgery (p < 0.001). Strong correlations were observed between tumor markers, with CA19-9 showing a positive correlation with CEA in both rPDAC (r = 0.550, p < 0.001) and mPDAC (r = 0.623, p = 0.002), while SYPL-1 demonstrated a negative correlation with CEA (r = −0.530, p = 0.009) in mPDAC. Receiver operating characteristic (ROC) analysis revealed excellent diagnostic performance for SYPL-1 in distinguishing both rPDAC (AUC = 0.965) and mPDAC (AUC = 0.985) from healthy controls, achieving superior accuracy compared to conventional markers CEA and CA19-9. Conclusions: Serum SYPL-1 emerges as a promising biomarker for the diagnosis and monitoring of rPDAC and mPDAC. Its significantly elevated levels in cancer groups, coupled with its marked decrease following surgical resection, suggest that SYPL-1 could play a critical role in both initial diagnosis and post-treatment surveillance. The strong correlations observed between SYPL-1, CEA, and CA19-9 further support its potential utility in a multi-marker panel. Notably, SYPL-1 demonstrated superior diagnostic accuracy compared to conventional markers, with high AUC values indicating its excellent ability to distinguish rPDAC and mPDAC from healthy controls. These findings highlight the need for further investigation to validate SYPL-1 as a reliable, non-invasive biomarker that could enhance early detection, prognosis, and treatment monitoring in rPDAC. Full article
(This article belongs to the Section Oncology)
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20 pages, 12613 KiB  
Article
Skimmianine Modulates Tumor Proliferation and Immune Dynamics in Breast Cancer by Targeting PCNA and TNF-α
by Tuğcan Korak, Hayat Ayaz and Fırat Aşır
Pharmaceuticals 2025, 18(5), 756; https://doi.org/10.3390/ph18050756 - 20 May 2025
Cited by 1 | Viewed by 704
Abstract
Background/Objectives: Breast cancer continues to be a major global health challenge, driving the urgent need for innovative therapeutic strategies. This study evaluates the anticancer and immunomodulatory potential of skimmianine in breast cancer through a comprehensive approach, integrating biochemical, histopathological, immunohistochemical, and bioinformatics [...] Read more.
Background/Objectives: Breast cancer continues to be a major global health challenge, driving the urgent need for innovative therapeutic strategies. This study evaluates the anticancer and immunomodulatory potential of skimmianine in breast cancer through a comprehensive approach, integrating biochemical, histopathological, immunohistochemical, and bioinformatics analyses. Methods: Thirty-six female Wistar albino rats were divided into three groups: control, 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer, and DMBA + skimmianine (n = 12/group). Breast cancer was induced with a single oral dose of 50 mg/kg DMBA in sesame oil. After 16 weeks, skimmianine (40 mg/kg) was administered intraperitoneally for four weeks. Serum CA15-3 levels were measured via enzyme-linked immunosorbent assay (ELISA). Histopathological assessment was performed using hematoxylin and eosin (H&E) staining, and proliferating cell nuclear antigen (PCNA) and tumor necrosis factor-alpha (TNF-α) were evaluated immunohistochemically. Pathway and hub gene analyses were performed using Cytoscape, functional annotation with Enrichr, and immune analyses via the Tumor and Immune System Interaction Database (TISIDB) and Sangerbox. Results: The tumor burden in the animals increased after DMBA induction compared to the control groups (0.00 ± 0.00% vs. 89.00 ± 6.60%, respectively, p < 0.001), while skimmianine treatment significantly reduced the tumor burden in the animals (49.00 ± 9.40%, vs. DMBA group, p = 0.191). Histopathological analysis showed DMBA-induced structural disorganization and malignant clustering, whereas skimmianine preserved ductal structures and mitigated the damage. Compared to the control group, DMBA administration markedly elevated serum CA15-3 levels (0.23 ± 0.06 ng/mL vs. 8.57 ± 1.01 ng/mL, respectively), along with PCNA (13.0 ± 3.0% vs. 25.0 ± 4.0%, respectively) and TNF-α (8.4 ± 1.7% vs. 34.0 ± 5.3%, respectively) expression, indicating active tumor progression. Skimmianine treatment significantly reduced CA15-3 (3.72 ± 0.58 ng/mL), PCNA (20.0 ± 4.1%), and TNF-α (25.0 ± 3.9%) levels (p < 0.001). In silico analyses indicated skimmianine’s effects on PCNA influence cell cycle pathways, while TNF-α suppression impacts toll-like receptor (TLR) signaling (adjusted p < 0.05). PCNA- and TNF-α-related anticancer effects were especially notable in basal molecular and C2 immune subtypes (p < 0.05). Related hub proteins may regulate immune dynamics by reducing immunosuppression and tumor-promoting inflammation (p < 0.05). Conclusions: Skimmianine shows promise as a breast cancer therapy by simultaneously targeting tumor growth and immune regulation, with PCNA and TNF-α identified as potential key players. Full article
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15 pages, 534 KiB  
Article
Effects of Tofacitinib Therapy on Circulating Tumour-Associated Antigens and Their Relationship with Clinical, Laboratory and Vascular Parameters in Rheumatoid Arthritis
by Enikő Sebestyén, Dóra Csige, Péter Antal-Szalmás, Ágnes Horváth, Edit Végh, Boglárka Soós, Zsófia Pethő, Nóra Bodnár, Attila Hamar, Levente Bodoki, Dorottya Kacsándi, Róza Földesi, Edit Kalina, Gábor Nagy, György Kerekes, Béla Nagy, Katalin Hodosi, Szilvia Szamosi, Péter Árkosy, Gabriella Szűcs, Zoltán Szekanecz and Éva Szekaneczadd Show full author list remove Hide full author list
Biomolecules 2025, 15(5), 648; https://doi.org/10.3390/biom15050648 - 30 Apr 2025
Viewed by 603
Abstract
Introduction: Tumour-associated antigens (TAA) have been implicated in cell adhesion and cancer metastasis formation, but also in inflammatory processes, such as rheumatoid arthritis (RA). There has been little information about the possible associations of TAAs with RA-related clinical and laboratory parameters, with impaired [...] Read more.
Introduction: Tumour-associated antigens (TAA) have been implicated in cell adhesion and cancer metastasis formation, but also in inflammatory processes, such as rheumatoid arthritis (RA). There has been little information about the possible associations of TAAs with RA-related clinical and laboratory parameters, with impaired vascular pathophysiology in RA, as well as about the effects of antirheumatic drugs on TAA production. Therefore, we determined the effects of one-year tofacitinib treatment on TAA levels, as well as correlations of TAA levels with various RA-associated and vascular parameters. Patients and methods: Altogether, 26 RA patients received 5 mg bid or 10 mg bid tofacitinib treatment for 12 months. Ultrasound-based functional vascular assessments, such as common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV), were determined at various timepoints. Serum concentrations of TAAs, including carcinoembryonic antigen (CEA), CA15-3, CA19-9, CA125, CA72-4, human epididymis protein 4 (HE4) and tissue polypeptide antigen (TPA), as well as various cytokines (TNF-α, IL-6, IL-8, VEGF) and PECAM-1 were determined by flow cytometry using a bead-based multiplex assay (LEGENDplex). Results: As previously determined and published, one-year tofacitinib treatment effectively suppressed disease activity and inflammation. Serum CA15-3 and HE4 levels significantly decreased both after 6 and 12 months compared to baseline (p < 0.05). CA19-9 levels significantly increased both after 6 and 12 months, while CEA levels transiently increased after 6 months versus baseline (p < 0.05). CA125, CA72-4 and TPA levels did not change over time. In various regression analyses, TAA levels showed variable, significant, positive associations with the 28-joint disease activity score (DAS28), CRP, ESR, RF, IL-6, TNF-α, IL-8 and PECAM-1 (p < 0.05). In addition, TAAs variably correlated with ccIMT and cfPWV (p < 0.05). Moreover, one-year changes in TAA levels variably correlated with DAS28, RF and some cytokines (p < 0.05), as well as with changes in DAS28, HAQ, CRP, ESR, IL-6, VEGF and ccIMT from baseline to 12 months (p < 0.05). Conclusions: JAK inhibition might decrease the levels of some TAAs and increase those of others. TAA levels might be associated with RA-related and vascular biomarkers. These results suggest that TAAs might play a role in inflammatory processes and vascular pathology underlying RA. Full article
(This article belongs to the Section Biological Factors)
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19 pages, 2925 KiB  
Article
Comprehensive Serum Glycopeptide Spectra Analysis Combined with Machine Learning for Early Detection of Lung Cancer: A Case–Control Study
by Koji Yamazaki, Shigeto Kawauchi, Masaki Okamoto, Kazuhiro Tanabe, Chihiro Hayashi, Mikio Mikami and Tetsuya Kusumoto
Cancers 2025, 17(9), 1474; https://doi.org/10.3390/cancers17091474 - 27 Apr 2025
Cited by 2 | Viewed by 663
Abstract
Background: Lung cancer is among the most prevalent and fatal cancers worldwide. Traditional diagnostic methods, such as computed tomography, are not ideal for screening due to their high cost and radiation exposure. In contrast, blood-based diagnostics, as non-invasive approaches, are expected to reduce [...] Read more.
Background: Lung cancer is among the most prevalent and fatal cancers worldwide. Traditional diagnostic methods, such as computed tomography, are not ideal for screening due to their high cost and radiation exposure. In contrast, blood-based diagnostics, as non-invasive approaches, are expected to reduce patient burden, thereby increasing screening participation and ultimately improving survival rates. However, conventional tumor markers have shown limited effectiveness in early detection. Methods: We recruited 199 patients with lung cancer and 590 healthy volunteers. Nine tumor markers (CEA, CA19-9, CYFRA, AFP, PSA, CA125, CA15-3, SCC antigen, and NCC-ST439) were analyzed, along with enriched glycopeptides (EGPs) derived from serum proteins using liquid chromatography–mass spectrometry. Machine learning models, including decision trees and deep learning approaches, were employed to develop a predictive model for accurately distinguishing lung cancer from healthy controls based on tumor markers and EGP profiles. Results: We found that α1-antitrypsin with fully sialylated biantennary glycan, attached to asparagine 271 (AT271-FSG), and α2-macroglobulin with fully sialylated biantennary glycan, attached to asparagine 70 (MG70-FSG), could significantly distinguish between patients with lung cancer and healthy individuals. Comprehensive Serum Glycopeptide Spectra Analysis (CSGSA), integrating nine conventional tumor markers and 1688 EGPs using a machine learning model, enhanced diagnostic accuracy and achieved an ROC-AUC score of 0.935. It also identified stage I cases with an ROC-AUC of 0.914, indicating the possibility of early-stage detection. The PPV reached 2.8%, which was sufficient for practical application. Conclusions: This method represents a significant advancement in cancer diagnostics, combining multiple biomarkers with cutting-edge machine learning to improve the early detection of lung cancer. Full article
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11 pages, 640 KiB  
Article
Neutrophil–Lymphocyte Ratio and KELIM Score as Prognostic Markers in High-Grade Serous Advanced Ovarian Cancer Patients Treated with Neoadjuvant Chemotherapy
by Vasilis Theodoulidis, Kalliopi Kissoudi, Kimon Chatzistamatiou, Panagiotis Tzitzis, Dimitris Zouzoulas, Iakovos Theodoulidis, Christos Anthoulakis, Theodoros Moysiadis, Maria Topalidou, Eleni Timotheadou, Grigoris Grimpizis and Dimitris Tsolakidis
Biomedicines 2025, 13(4), 975; https://doi.org/10.3390/biomedicines13040975 - 16 Apr 2025
Viewed by 588
Abstract
Background/Objectives: Advanced ovarian cancer (AOC) is frequently diagnosed at late stages, with a 5-year overall survival (OS) rate of approximately 25%. While primary debulking surgery followed by chemotherapy remains the standard treatment, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is [...] Read more.
Background/Objectives: Advanced ovarian cancer (AOC) is frequently diagnosed at late stages, with a 5-year overall survival (OS) rate of approximately 25%. While primary debulking surgery followed by chemotherapy remains the standard treatment, neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is an alternative for patients with extensive disease. Achieving complete cytoreduction is a critical prognostic factor for OS and progression-free survival (PFS). This study evaluated the prognostic value of two biomarkers—the neutrophil–lymphocyte ratio (NLR) and the cancer antigen-125 (CA-125) ELIMination rate constant K (KELIM)—in predicting survival outcomes and recurrence rates in patients with AOC undergoing NACT. Methods: A retrospective, single-center analysis was conducted on 78 patients with high-grade serous AOC (stages III–IV) treated with platinum-based NACT followed by IDS between January 2013 and December 2023. NLR was calculated from prechemotherapy complete blood counts, with a threshold of ≥3 indicating elevated levels. KELIM, a marker of tumor chemosensitivity, was derived from CA-125 kinetics during the first 100 days of chemotherapy, with a cutoff of ≥1 denoting a favorable outcome. Clinical outcomes, including PFS and OS were analyzed using Kaplan–Meier survival curves, log-rank tests, and Cox regression models. Results: Results demonstrated that elevated NLR (≥3) and low KELIM (<1) were associated with poorer PFS and OS. KELIM score was identified as a strong prognostic marker for both PFS and OS, while NLR demonstrated weak association. Complete cytoreduction was achieved in 69.2% of patients, significantly correlating with improved survival outcomes. Postoperative complications, assessed using the Clavien–Dindo classification, were observed in a small subset of patients, with a total median hospital stay of 8 days. Conclusions: This study highlights the potential of NLR and KELIM as prognostic tools in AOC, aiding in patient selection for radical surgical interventions and predicting chemosensitivity. Future multicenter studies with larger cohorts are needed to validate these results and further explore the clinical utility of these biomarkers in optimizing treatment strategies for AOC. Full article
(This article belongs to the Special Issue Advanced Research in Gynecologic Oncology)
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