International Journal of Molecular Sciences

Research

11 pages, 1376 KiB

Open AccessArticle

Diagnostic Performance of Next-Generation Sequencing (NGS) in Indeterminate Thyroid Nodules: A Single Hospital Experience

by Marco Capezzone, Maja Rossi, Sara Bardi, Eugenia Maria Morabito, Gilda Dalmazio, Giuseppe Iapichino, Simona Galassi, Serena Seralessandri, Liborio Torregrossa, Massimo Tosti Balducci, Elio Marchetti, Massimo Alessandri, Agostino Ognibene, Luigi De Napoli, Gabriele Materazzi, Silvia Cantara and Anello Marcello Poma

Int. J. Mol. Sci. 2025, 26(9), 4225; https://doi.org/10.3390/ijms26094225 - 29 Apr 2025

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Abstract

Fine-needle aspiration cytology (FNAC) is the gold standard to diagnose thyroid nodules but fails in discriminating the nature of indeterminate lesions. Molecular testing can improve the diagnosis of these nodules and next-generation sequencing (NGS) can be used to test many genes simultaneously. Assess [...] Read more.

Fine-needle aspiration cytology (FNAC) is the gold standard to diagnose thyroid nodules but fails in discriminating the nature of indeterminate lesions. Molecular testing can improve the diagnosis of these nodules and next-generation sequencing (NGS) can be used to test many genes simultaneously. Assess the performance of an NGS 17-gene panel on thyroid indeterminate FNAC. One hundred five indeterminate FNACs, 30.5% high-risk (TIR3B) and 69.5% low-risk (TIR3A), were analyzed by NGS. For TIR3A, the rate of mutated samples was 10.9%, significantly lower (p = 0.0001) compared to TIR3B (63.6%). Twenty-two mutated and fourteen non-mutated samples were submitted to surgery. At histology, the overall malignancy was 85.7% in the indeterminate group that had a positive molecular test and 13.3% in the mutation-negative (p = 0.01). The 17-gene panel had a sensitivity of 90%, specificity of 87%, positive predictive value (PPV) of 91%, and negative predictive value (NPV) of 87%. We reported the utility of Ultrasound Malignancy Risk Stratification of Thyroid Nodules in Adults (EU-TIRADS) in selecting indeterminate nodules for molecular analysis, showing a significant correlation between US score and mutation (p = 0.004). The performance of a 17-gene panel based on NGS technology is promising, allowing the selection of indeterminate nodules to submit to surgery with a great specificity and PPV. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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10 pages, 462 KiB

Open AccessArticle

Germline Genetic Testing in Patients with Bone and Soft Tissue Sarcoma: A Prospective Multicenter Study to Evaluate Cancer Susceptibility

by Isaak Ailts, Michael A. Golafshar, Katie L. Kunze, Margaret Klint, Kathleen Barrus, Robert L. Nussbaum, Edward D. Esplin, Brandie Leach, Sarah Young, N. Jewel Samadder and Mahesh Seetharam

Int. J. Mol. Sci. 2025, 26(7), 2839; https://doi.org/10.3390/ijms26072839 - 21 Mar 2025

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Abstract

Sarcomas are rare heterogenous mesenchymal tumors with over seventy-five different subtypes, with varying biology and outcomes, with no clear inciting factor in the vast majority. To determine the prevalence of pathogenic germline variants (PGV) in patients with sarcomas, we undertook a prospective multi-site [...] Read more.

Sarcomas are rare heterogenous mesenchymal tumors with over seventy-five different subtypes, with varying biology and outcomes, with no clear inciting factor in the vast majority. To determine the prevalence of pathogenic germline variants (PGV) in patients with sarcomas, we undertook a prospective multi-site study of germline sequencing using an 84-gene next-generation sequencing panel among patients receiving care at the four Mayo Clinic Cancer Centers. Of 115 patients with bone and soft tissue sarcoma, the median age was 60 years, 49.6% were female, 82.6% were White. The anatomical location of the primary tumor included extremities (34.8%), retroperitoneum (19.1%), trunk (13.0%), and head and neck (7.8%). Family history of cancer was present in 62.6% of the study population. Ten patients (8.7%) had a pathogenic/likely pathogenic variant (PGV). Of these, three had stage IV sarcoma, and seven had earlier-stage sarcoma (stages I–III). Among the 55 (48.7%) patients who had variant of uncertain significance (VUS), 41.1% (22/55) had stage IV sarcoma and 58.9% (33/55) had earlier-stage disease. Of the ten patients with PGV, high-to-moderate penetrance gene abnormalities were identified in eight patients (80%) involving TP53 (3), BRCA1 (1), SDHA (1), ATM (2), and NBN (1) genes. The vast majority of the PGVs (70%) would not have been detected using the current guidelines. Because of the paucity of sarcomas and lack of effective treatment options for advanced disease, germline testing in sarcomas represents a potentially impactful strategy to assess therapeutic options and for assessment of familial risk. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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21 pages, 7489 KiB

Open AccessArticle

Anthocyanins in Black Soybean Coats Promote Apoptosis in Hepatocellular Carcinoma Cells by Regulating the JAK2/STAT3 Pathway

by Yuying Li, Miaomiao Wang, Jinjing Bai, Xin Li, Sheng Xiao and Li Song

Int. J. Mol. Sci. 2025, 26(3), 1070; https://doi.org/10.3390/ijms26031070 - 26 Jan 2025

Viewed by 695

Abstract

The use of black soybean (Glycine max L.), an edible crop prevalent in Asia, has attracted attention for its hepatoprotective properties. Notably, the anthocyanin components in black soybean coats have shown potential in inhibiting tumor growth. Here, anthocyanins were extracted from black [...] Read more.

The use of black soybean (Glycine max L.), an edible crop prevalent in Asia, has attracted attention for its hepatoprotective properties. Notably, the anthocyanin components in black soybean coats have shown potential in inhibiting tumor growth. Here, anthocyanins were extracted from black soybean coats using both microwave and water bath methods. The physicochemical characteristics of black soybean coat anthocyanins (BSCAs) and their biological activities were examined. The results from the MTT and EDU assays demonstrated a dose-dependent inhibitory effect of BSCAs on hepatocellular carcinoma HepG2 cells, while leaving normal cells unaffected. Flow cytometry and mitochondrial membrane potential assays revealed that BSCA treatment induces apoptosis in HepG2 cells. A network pharmacology approach was employed to explore the relationship between hepatocellular carcinoma and the active ingredients of BSCAs, identifying the JAK/STAT signaling pathway as a potential target. Molecular docking studies confirmed the interaction between BSCA components and JAK2/STAT3 targets. Subsequent Western blot and qPCR experiments validated that BSCAs promote apoptosis in HepG2 cells by modulating the JAK2/STAT3 signaling pathway. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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20 pages, 6576 KiB

Open AccessArticle

Enhancing Clinical Applications by Evaluation of Sensitivity and Specificity in Whole Exome Sequencing

by Youngbeen Moon, Chung Hwan Hong, Young-Ho Kim, Jong-Kwang Kim, Seo-Hyeon Ye, Eun-Kyung Kang, Hye Won Choi, Hyeri Cho, Hana Choi, Dong-eun Lee, Yongdoo Choi, Tae-Min Kim, Seong Gu Heo, Namshik Han and Kyeong-Man Hong

Int. J. Mol. Sci. 2024, 25(24), 13250; https://doi.org/10.3390/ijms252413250 - 10 Dec 2024

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Abstract

The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, and CC) using reference standards composed of DNA from hydatidiform mole and individual blood at various [...] Read more.

The cost-effectiveness of whole exome sequencing (WES) remains controversial due to variant call variability, necessitating sensitivity and specificity evaluation. WES was performed by three companies (AA, BB, and CC) using reference standards composed of DNA from hydatidiform mole and individual blood at various ratios. Sensitivity was assessed by the detection rate of null–homozygote (N–H) alleles at expected variant allelic fractions, while false positive (FP) errors were counted for unexpected alleles. Sensitivity was approximately 20% for in-house results from BB and CC and around 5% for AA. Dynamic Read Analysis for GENomics (DRAGEN) analyses identified 1.34 to 1.71 times more variants, detecting over 96% of in-house variants, with sensitivity for common variants increasing to 5%. In-house FP errors varied significantly among companies (up to 13.97 times), while DRAGEN minimized this variation. Despite DRAGEN showing higher FP errors for BB and CC, the increased sensitivity highlights the importance of effective bioinformatic conditions. We also assessed the potential effects of target enrichment and proposed optimal cutoff values for the read depth and variant allele fraction in WES. Optimizing bioinformatic analysis based on sensitivity and specificity from reference standards can enhance variant detection and improve the clinical utility of WES. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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8 pages, 837 KiB

Open AccessCommunication

Single Nucleotide Polymorphisms on Toll-like Receptor-4 and the Risk of Developing Skin Cancer

by Nabiha Yusuf, Noha Sharafeldin, Mohammad Saleem, Tom Callens, Ludwine M. Messiaen and Craig A. Elmets

Int. J. Mol. Sci. 2024, 25(23), 12728; https://doi.org/10.3390/ijms252312728 - 27 Nov 2024

Viewed by 804

Abstract

Exposure to solar ultraviolet (UV) radiation is an established risk factor for skin cancer. Toll-like receptor-4 (TLR4)-mediated immune dysregulation has emerged as a key mechanism for the detrimental effects of acute and chronic UV exposure and skin cancer in mice. Single nucleotide polymorphisms [...] Read more.

Exposure to solar ultraviolet (UV) radiation is an established risk factor for skin cancer. Toll-like receptor-4 (TLR4)-mediated immune dysregulation has emerged as a key mechanism for the detrimental effects of acute and chronic UV exposure and skin cancer in mice. Single nucleotide polymorphisms (SNPs) on the TLR4 gene have been reported to increase or decrease susceptibility to various cancers in other organs. There is limited information on TLR4 SNPs and susceptibility to human keratinocyte carcinomas. The study’s objective is to test the association between TLR4 SNPs and the risk of developing keratinocyte carcinomas. Skin cancer patients and controls at the University of Alabama at Birmingham completed a cross-sectional survey on personal and family history of skin cancer as well as on sunscreen use and tanning proneness. Peripheral blood samples were obtained from participants, and DNA was extracted to genotype the TLR4 SNPs. Descriptive analytics were used to describe the cohort. Multivariable logistic regression models were used to assess the association between TLR4 SNPs and skin cancer risk. The sample consisted of a cohort of 93 skin cancer patients over the age of 50 and 94 controls; 33.3% of cases and 44.7% of controls were females; 12.9% of cases and 17% of controls had a TLR4 SNP. The most common SNP was D299G/T399I in 9.7% of skin cancer patients and 13.8% of controls. We did not find a statistically significant association between the D299G/T399I SNP and skin cancer (odds ratio (OR) = 0.34, 95% CI: 0.11, 1.07, p = 0.065) adjusting for age, sex, eye color, actinic keratosis, sunscreen use and reapplication, and family history of skin cancer. Based on our findings from our limited cohort of participants, we found some protective effect for the TLR4 SNP for skin cancer, which was not statistically significant. Validation of these findings in a larger cohort is warranted. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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15 pages, 11654 KiB

Open AccessArticle

The Anthraquinone Derivative C2 Enhances Oxaliplatin-Induced Cell Death and Triggers Autophagy via the PI3K/AKT/mTOR Pathway

by Yuying Li, Wei Yan, Yu Qin, Liwei Zhang and Sheng Xiao

Int. J. Mol. Sci. 2024, 25(12), 6468; https://doi.org/10.3390/ijms25126468 - 12 Jun 2024

Viewed by 1437

Abstract

Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our previous study found that compound 1-nitro-2 acyl anthraquinone-leucine (C2) exhibited excellent anti-colorectal cancer (CRC) activity involving autophagy and [...] Read more.

Chemotherapy resistance in cancer is an essential factor leading to high mortality rates. Tumor multidrug resistance arises as a result of the autophagy process. Our previous study found that compound 1-nitro-2 acyl anthraquinone-leucine (C2) exhibited excellent anti-colorectal cancer (CRC) activity involving autophagy and apoptosis-related proteins, whereas its underlying mechanism remains unclear. A notable aspect of this study is how C2 overcomes the multidrug susceptibility of HCT116/L-OHP, a colon cancer cell line that is resistant to both in vitro and in vivo oxaliplatin (trans-/-diaminocyclohexane oxalatoplatinum; L-OHP). In a xenograft tumor mouse model, we discovered that the mixture of C2 and L-OHP reversed the resistance of HCT116/L-OHP cells to L-OHP and inhibited tumor growth; furthermore, C2 down-regulated the gene expression levels of P-gp and BCRP and decreased P-gp’s drug efflux activity. It is important to note that while C2 re-sensitized the HCT116/L-OHP cells to L-OHP for apoptosis, it also triggered a protective autophagic pathway. The expression levels of cleaved caspase-3 and Beclin 1 steadily rose. Expression of PI3K, phosphorylated AKT, and mTOR were decreased, while p53 increased. We demonstrated that the anthraquinone derivative C2 acts as an L-OHP sensitizer and reverses resistance to L-OHP in HCT116/L-OHP cells. It suggests that C2 can induce autophagy in HCT116/L-OHP cells by mediating p53 and the PI3K/AKT/mTOR signaling pathway. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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15 pages, 6377 KiB

Open AccessArticle

Effects of Reduced Extracellular Sodium Concentrations on Cisplatin Treatment in Human Tumor Cells: The Role of Autophagy

by Laura Naldi, Benedetta Fibbi, Cecilia Anceschi, Patrizia Nardini, Daniele Guasti, Alessandro Peri and Giada Marroncini

Int. J. Mol. Sci. 2024, 25(8), 4377; https://doi.org/10.3390/ijms25084377 - 16 Apr 2024

Cited by 3 | Viewed by 1530

Abstract

Hyponatremia is the prevalent electrolyte imbalance in cancer patients, and it is associated with a worse outcome. Notably, emerging clinical evidence suggests that hyponatremia adversely influences the response to anticancer treatments. Therefore, this study aims to investigate how reduced extracellular [Na⁺] [...] Read more.

Hyponatremia is the prevalent electrolyte imbalance in cancer patients, and it is associated with a worse outcome. Notably, emerging clinical evidence suggests that hyponatremia adversely influences the response to anticancer treatments. Therefore, this study aims to investigate how reduced extracellular [Na⁺] affects the responsiveness of different cancer cell lines (from human colon adenocarcinoma, neuroblastoma, and small cell lung cancer) to cisplatin and the underlying potential mechanisms. Cisplatin dose–response curves revealed higher IC50 in low [Na⁺] than normal [Na⁺]. Accordingly, cisplatin treatment was less effective in counteracting the proliferation and migration of tumor cells when cultured in low [Na⁺], as demonstrated by colony formation and invasion assays. In addition, the expression analysis of proteins involved in autophagosome–lysosome formation and the visualization of lysosomal areas by electron microscopy revealed that one of the main mechanisms involved in chemoresistance to cisplatin is the promotion of autophagy. In conclusion, our data first demonstrate that the antitumoral effect of cisplatin is markedly reduced in low [Na⁺] and that autophagy is an important mechanism of drug escape. This study indicates the role of hyponatremia in cisplatin chemoresistance and reinforces the recommendation to correct this electrolyte alteration in cancer patients. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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17 pages, 4786 KiB

Open AccessArticle

Disrupting Poly(ADP-ribosyl)ating Pathway Creates Premalignant Conditions in Mammalian Liver

by Yaroslava Karpova, David J. Orlicky, Edward E. Schmidt and Alexei V. Tulin

Int. J. Mol. Sci. 2023, 24(24), 17205; https://doi.org/10.3390/ijms242417205 - 6 Dec 2023

Cited by 1 | Viewed by 1750

Abstract

Hepatocellular carcinoma (HCC) is a major global health concern, representing one of the leading causes of cancer-related deaths. Despite various treatment options, the prognosis for HCC patients remains poor, emphasizing the need for a deeper understanding of the factors contributing to HCC development. [...] Read more.

Hepatocellular carcinoma (HCC) is a major global health concern, representing one of the leading causes of cancer-related deaths. Despite various treatment options, the prognosis for HCC patients remains poor, emphasizing the need for a deeper understanding of the factors contributing to HCC development. This study investigates the role of poly(ADP-ribosyl)ation in hepatocyte maturation and its impact on hepatobiliary carcinogenesis. A conditional Parg knockout mouse model was employed, utilizing Cre recombinase under the albumin promoter to target Parg depletion specifically in hepatocytes. The disruption of the poly(ADP-ribosyl)ating pathway in hepatocytes affects the early postnatal liver development. The inability of hepatocytes to finish the late maturation step that occurs early after birth causes intensive apoptosis and acute inflammation, resulting in hypertrophic liver tissue with enlarged hepatocytes. Regeneration nodes with proliferative hepatocytes eventually replace the liver tissue and successfully fulfill the liver function. However, early developmental changes predispose these types of liver to develop pathologies, including with a malignant nature, later in life. In a chemically induced liver cancer model, Parg-depleted livers displayed a higher tendency for hepatocellular carcinoma development. This study underscores the critical role of the poly(ADP-ribosyl)ating pathway in hepatocyte maturation and highlights its involvement in liver pathologies and hepatobiliary carcinogenesis. Understanding these processes may provide valuable insights into liver biology and liver-related diseases, including cancer. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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Review

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26 pages, 2304 KiB

Open AccessReview

Single-Cell Sequencing: Genomic and Transcriptomic Approaches in Cancer Cell Biology

by Ana Ortega-Batista, Yanelys Jaén-Alvarado, Dilan Moreno-Labrador, Natasha Gómez, Gabriela García and Erika N. Guerrero

Int. J. Mol. Sci. 2025, 26(5), 2074; https://doi.org/10.3390/ijms26052074 - 27 Feb 2025

Cited by 1 | Viewed by 1953

Abstract

This article reviews the impact of single-cell sequencing (SCS) on cancer biology research. SCS has revolutionized our understanding of cancer and tumor heterogeneity, clonal evolution, and the complex interplay between cancer cells and tumor microenvironment. SCS provides high-resolution profiling of individual cells in [...] Read more.

This article reviews the impact of single-cell sequencing (SCS) on cancer biology research. SCS has revolutionized our understanding of cancer and tumor heterogeneity, clonal evolution, and the complex interplay between cancer cells and tumor microenvironment. SCS provides high-resolution profiling of individual cells in genomic, transcriptomic, and epigenomic landscapes, facilitating the detection of rare mutations, the characterization of cellular diversity, and the integration of molecular data with phenotypic traits. The integration of SCS with multi-omics has provided a multidimensional view of cellular states and regulatory mechanisms in cancer, uncovering novel regulatory mechanisms and therapeutic targets. Advances in computational tools, artificial intelligence (AI), and machine learning have been crucial in interpreting the vast amounts of data generated, leading to the identification of new biomarkers and the development of predictive models for patient stratification. Furthermore, there have been emerging technologies such as spatial transcriptomics and in situ sequencing, which promise to further enhance our understanding of tumor microenvironment organization and cellular interactions. As SCS and its related technologies continue to advance, they are expected to drive significant advances in personalized cancer diagnostics, prognosis, and therapy, ultimately improving patient outcomes in the era of precision oncology. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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12 pages, 526 KiB

Open AccessReview

Neurotensin and Its Involvement in Female Hormone-Sensitive Cancers

by Ninon Bertrand, Romane Mougel, George Riley, Marie Bruand, Guillaume Gauchotte and Mikaël Agopiantz

Int. J. Mol. Sci. 2024, 25(21), 11648; https://doi.org/10.3390/ijms252111648 - 30 Oct 2024

Cited by 1 | Viewed by 1134

Abstract

Neurotensin (NT) is a peptide involved in digestion, neuromodulation, and cancer progression. NT and its receptors (NTR1 and SORT1 mainly) have been widely studied in oncology. Data show that NT expression is under the control of sex steroid hormones, in particular estradiol. We [...] Read more.

Neurotensin (NT) is a peptide involved in digestion, neuromodulation, and cancer progression. NT and its receptors (NTR1 and SORT1 mainly) have been widely studied in oncology. Data show that NT expression is under the control of sex steroid hormones, in particular estradiol. We focused on its involvement in three main female hormone-sensitive cancers, breast, ovarian, and endometrial cancer, in a narrative review. NT, NTR1, and SORT1 are mostly expressed in these three cancers, and their involvement in oncologic processes such as proliferation and invasion seems to match, as does their impact on prognosis for most. The development of NT receptor-targeted therapies, including theranostics and radioligand treatments, presents a promising avenue for personalized cancer treatment. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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21 pages, 728 KiB

Open AccessReview

Leveraging PARP-1/2 to Target Distant Metastasis

by Mallory I. Frederick, Djihane Abdesselam, Anna Clouvel, Laurent Croteau and Saima Hassan

Int. J. Mol. Sci. 2024, 25(16), 9032; https://doi.org/10.3390/ijms25169032 - 20 Aug 2024

Cited by 2 | Viewed by 2557

Abstract

Poly (ADP-Ribose) Polymerase (PARP) inhibitors have changed the outcomes and therapeutic strategy for several cancer types. As a targeted therapeutic mainly for patients with BRCA1/2 mutations, PARP inhibitors have commonly been exploited for their capacity to prevent DNA repair. In this review, we [...] Read more.

Poly (ADP-Ribose) Polymerase (PARP) inhibitors have changed the outcomes and therapeutic strategy for several cancer types. As a targeted therapeutic mainly for patients with BRCA1/2 mutations, PARP inhibitors have commonly been exploited for their capacity to prevent DNA repair. In this review, we discuss the multifaceted roles of PARP-1 and PARP-2 beyond DNA repair, including the impact of PARP-1 on chemokine signalling, immune modulation, and transcriptional regulation of gene expression, particularly in the contexts of angiogenesis and epithelial-to-mesenchymal transition (EMT). We evaluate the pre-clinical role of PARP inhibitors, either as single-agent or combination therapies, to block the metastatic process. Efficacy of PARP inhibitors was demonstrated via DNA repair-dependent and independent mechanisms, including DNA damage, cell migration, invasion, initial colonization at the metastatic site, osteoclastogenesis, and micrometastasis formation. Finally, we summarize the recent clinical advancements of PARP inhibitors in the prevention and progression of distant metastases, with a particular focus on specific metastatic sites and PARP-1 selective inhibitors. Overall, PARP inhibitors have demonstrated great potential in inhibiting the metastatic process, pointing the way for greater use in early cancer settings. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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19 pages, 615 KiB

Open AccessReview

Exploring Potential Biomarkers in Oesophageal Cancer: A Comprehensive Analysis

by Adrianna Romanowicz, Marta Lukaszewicz-Zajac and Barbara Mroczko

Int. J. Mol. Sci. 2024, 25(8), 4253; https://doi.org/10.3390/ijms25084253 - 11 Apr 2024

Cited by 4 | Viewed by 2515

Abstract

Oesophageal cancer (OC) is the sixth leading cause of cancer-related death worldwide. OC is highly aggressive, primarily due to its late stage of diagnosis and poor prognosis for patients’ survival. Therefore, the establishment of new biomarkers that will be measured with non-invasive techniques [...] Read more.

Oesophageal cancer (OC) is the sixth leading cause of cancer-related death worldwide. OC is highly aggressive, primarily due to its late stage of diagnosis and poor prognosis for patients’ survival. Therefore, the establishment of new biomarkers that will be measured with non-invasive techniques at low cost is a critical issue in improving the diagnosis of OC. In this review, we summarize several original studies concerning the potential significance of selected chemokines and their receptors, including inflammatory proteins such as interleukin-6 (IL-6) and C-reactive protein (CRP), hematopoietic growth factors (HGFs), claudins (CLDNs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), adamalysines (ADAMs), as well as DNA- and RNA-based biomarkers, in OC. The presented results indicate the significant correlation between the CXCL12, CXCR4, CXCL8/CXCR2, M-CSF, MMP-2, MMP-9 ADAM17, ADAMTS-6, and CLDN7 levels and tumor stage, as well as the clinicopathological parameters of OC, such as the presence of lymph node and/or distant metastases. CXCL12, CXCL8/CXCR2, IL-6, TIMP-2, ADAM9, and ADAMTS-6 were prognostic factors for the overall survival of OC patients. Furthermore, IL-6, CXCR4, CXCL8, and MMP-9 indicate higher diagnostic utility based on the area under the ROC curve (AUC) than well-established OC tumor markers, whereas CLDN18.2 can be used in novel targeted therapies for OC patients. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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Other

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8 pages, 514 KiB

Open AccessHypothesis

Alpha Satellite DNA in Targeted Drug Therapy for Prostate Cancer

by Isidoro Feliciello and Đurđica Ugarković

Int. J. Mol. Sci. 2023, 24(21), 15585; https://doi.org/10.3390/ijms242115585 - 25 Oct 2023

Viewed by 1671

Abstract

Prostate cancer is the most common solid cancer in men and, despite the development of many new therapies, metastatic castration-resistant prostate cancer still remains a deadly disease. Therefore, novel concepts for the treatment of metastatic prostate cancer are needed. In our opinion, the [...] Read more.

Prostate cancer is the most common solid cancer in men and, despite the development of many new therapies, metastatic castration-resistant prostate cancer still remains a deadly disease. Therefore, novel concepts for the treatment of metastatic prostate cancer are needed. In our opinion, the role of the non-coding part of the genome, satellite DNA in particular, has been underestimated in relation to diseases such as cancer. Here, we hypothesise that this part of the genome should be considered as a potential target for the development of new drugs. Specifically, we propose a novel concept directed at the possible treatment of metastatic prostate cancer that is mostly based on epigenetics. Namely, metastatic prostate cancer is characterized by the strongly induced transcription of alpha satellite DNA located in pericentromeric heterochromatin and, according to our hypothesis, the stable controlled transcription of satellite DNA might be important in terms of the control of disease development. This can be primarily achieved through the epigenetic regulation of pericentromeric heterochromatin by using specific enzymes as well as their activators/inhibitors that could act as potential anti-prostate cancer drugs. We believe that our concept is innovative and should be considered in the potential treatment of prostate cancer in combination with other more conventional therapies. Full article

(This article belongs to the Special Issue Cancer Biology: From Genetic Aspects to Treatment)

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