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12 pages, 891 KiB

Open AccessArticle

Liquid Biopsy for Detection of Pancreaticobiliary Cancers by Functional Enrichment and Immunofluorescent Profiling of Circulating Tumor Cells and Their Clusters

by Andrew Gaya, Nitesh Rohatgi, Sewanti Limaye, Aditya Shreenivas, Ramin Ajami, Dadasaheb Akolkar, Vineet Datta, Ajay Srinivasan and Darshana Patil

Cancers 2024, 16(7), 1400; https://doi.org/10.3390/cancers16071400 - 2 Apr 2024

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Abstract

Circulating tumor cells (CTCs) have historically been used for prognostication in oncology. We evaluate the performance of liquid biopsy CTC assay as a diagnostic tool in suspected pancreaticobiliary cancers (PBC). The assay utilizes functional enrichment of CTCs followed by immunofluorescent profiling of organ-specific [...] Read more.

Circulating tumor cells (CTCs) have historically been used for prognostication in oncology. We evaluate the performance of liquid biopsy CTC assay as a diagnostic tool in suspected pancreaticobiliary cancers (PBC). The assay utilizes functional enrichment of CTCs followed by immunofluorescent profiling of organ-specific markers. The performance of the assay was first evaluated in a multicentric case-control study of blood samples from 360 participants, including 188 PBC cases (pre-biopsy samples) and 172 healthy individuals. A subsequent prospective observational study included pre-biopsy blood samples from 88 individuals with suspicion of PBC and no prior diagnosis of cancer. CTCs were harvested using a unique functional enrichment method and used for immunofluorescent profiling for CA19.9, Maspin, EpCAM, CK, and CD45, blinded to the tissue histopathological diagnosis. TruBlood^® malignant or non-malignant predictions were compared with tissue diagnoses to establish sensitivity and specificity. The test had 95.9% overall sensitivity (95% CI: 86.0–99.5%) and 92.3% specificity (95% CI: 79.13% to 98.38%) to differentiate PBC (n = 49) from benign conditions (n = 39). The high accuracy of the CTC-based TruBlood test demonstrates its potential clinical application as a diagnostic tool to assist the effective detection of PBC when tissue sampling is unviable or inconclusive. Full article

(This article belongs to the Special Issue Cancer Biomarkers: Recent Progress, Innovations and Future Clinical Implications)

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17 pages, 1776 KiB

Open AccessArticle

The Impact of Mutational Hotspots on Cancer Survival

by Melissa Gonzalez-Cárdenas and Víctor Treviño

Cancers 2024, 16(5), 1072; https://doi.org/10.3390/cancers16051072 - 6 Mar 2024

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Abstract

Background: Cofactors, biomarkers, and the mutational status of genes such as TP53, EGFR, IDH1/2, or PIK3CA have been used for patient stratification. However, many genes exhibit recurrent mutational positions known as hotspots, specifically linked to varying degrees of survival outcomes. Nevertheless, few hotspots [...] Read more.

Background: Cofactors, biomarkers, and the mutational status of genes such as TP53, EGFR, IDH1/2, or PIK3CA have been used for patient stratification. However, many genes exhibit recurrent mutational positions known as hotspots, specifically linked to varying degrees of survival outcomes. Nevertheless, few hotspots have been analyzed (e.g., TP53 and EGFR). Thus, many other genes and hotspots remain unexplored. Methods: We systematically screened over 1400 hotspots across 33 TCGA cancer types. We compared the patients carrying a hotspot against (i) all cases, (ii) gene-mutated cases, (iii) other mutated hotspots, or (iv) specific hotspots. Due to the limited number of samples in hotspots and the inherent group imbalance, besides Cox models and the log-rank test, we employed VALORATE to estimate their association with survival precisely. Results: We screened 1469 hotspots in 6451 comparisons, where 314 were associated with survival. Many are discussed and linked to the current literature. Our findings demonstrate associations between known hotspots and survival while also revealing more potential hotspots. To enhance accessibility and promote further investigation, all the Kaplan–Meier curves, the log-rank tests, Cox statistics, and VALORATE-estimated null distributions are accessible on our website. Conclusions: Our analysis revealed both known and putatively novel hotspots associated with survival, which can be used as biomarkers. Our web resource is a valuable tool for cancer research. Full article

(This article belongs to the Special Issue Cancer Biomarkers: Recent Progress, Innovations and Future Clinical Implications)

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10 pages, 1237 KiB

Open AccessArticle

Prognostic Value of Apparent Diffusion Coefficient (ADC) in Patients with Diffuse Gliomas

by Marija Bušić, Zoran Rumboldt, Dora Čerina, Željko Bušić and Krešimir Dolić

Cancers 2024, 16(4), 681; https://doi.org/10.3390/cancers16040681 - 6 Feb 2024

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Abstract

This study aimed to evaluate potential posttreatment changes in ADC values within the tissue surrounding the enhancing lesion, particularly in areas not exhibiting MRI characteristics of involvement. Additionally, the objective was to investigate the correlations among ADC values, treatment response, and survival outcomes [...] Read more.

This study aimed to evaluate potential posttreatment changes in ADC values within the tissue surrounding the enhancing lesion, particularly in areas not exhibiting MRI characteristics of involvement. Additionally, the objective was to investigate the correlations among ADC values, treatment response, and survival outcomes in individuals diagnosed with gliomas. This retrospective study included a total of 49 patients that underwent either stereotactic biopsy or maximal surgical resection. Histologically confirmed as Grade III or IV gliomas, all cases adhered to the 2016 and 2021 WHO classifications, with subsequent radio-chemotherapy administered post-surgery. Patients were divided into two groups: short and long survival groups. Baseline and follow-up MRI scans were obtained on a 1.5 T MRI scanner. Two ROI circles were positioned near the enhancing area, one ROI in the NAWM ipsilateral to the neoplasm and another symmetrically in the contralateral hemisphere on ADC maps. At follow-up there was a significant difference in both ipsilateral and contralateral NAWM between the two groups, −0.0857 (p = 0.004) and −0.0607 (p = 0.037), respectively. There was a weak negative correlation between survival and ADC values in ipsilateral and contralateral NAWM at the baseline with the correlation coefficient −0.328 (p = 0.02) and −0.302 (p = 0.04), respectively. The correlation was stronger at the follow-up. The findings indicate that ADC values in normal-appearing white matter (NAWM) may function as a prognostic biomarker in patients with diffuse gliomas. Full article

(This article belongs to the Special Issue Cancer Biomarkers: Recent Progress, Innovations and Future Clinical Implications)

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18 pages, 1796 KiB

Open AccessArticle

Multi-Institutional Evaluation of Pathologists’ Assessment Compared to Immunoscore

by Joseph Willis, Robert A. Anders, Toshihiko Torigoe, Yoshihiko Hirohashi, Carlo Bifulco, Inti Zlobec, Bernhard Mlecnik, Sandra Demaria, Won-Tak Choi, Pavel Dundr, Fabiana Tatangelo, Annabella Di Mauro, Pamela Baldin, Gabriela Bindea, Florence Marliot, Nacilla Haicheur, Tessa Fredriksen, Amos Kirilovsky, Bénédicte Buttard, Angela Vasaturo, Lucie Lafontaine, Pauline Maby, Carine El Sissy, Assia Hijazi, Amine Majdi, Christine Lagorce, Anne Berger, Marc Van den Eynde, Franck Pagès, Alessandro Lugli and Jérôme Galon Show full author list Hide full author list

Cancers 2023, 15(16), 4045; https://doi.org/10.3390/cancers15164045 - 10 Aug 2023

Cited by 4 | Viewed by 1341

Abstract

Background: The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists’ visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. Methods: An international group of [...] Read more.

Background: The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists’ visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification. Methods: An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists’ T-score, corresponding hematoxylin–eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS. Results: Non-concordant T-scores were reported in more than 92% of cases. Disagreement between semi-quantitative visual assessment of T-score and the reference IS was observed in 91% and 96% of cases before and after training, respectively. Statistical analyses showed that the concordance index between pathologists and the digital IS was weak in two- and three-category IS, respectively. After training, 42% of cases had a change in T-score, but no improvement was observed with a Kappa of 0.465 and 0.374. For the 20% of patients around the cut points, no concordance was observed between pathologists and digital pathology analysis in both two- and three-category IS, before or after training (all Kappa < 0.12). Conclusions: The standardized IS assay outperformed expert pathologists’ T-score evaluation in the clinical setting. This study demonstrates that digital pathology, in particular digital IS, represents a novel generation of immune pathology tools for reproducible and quantitative assessment of tumor-infiltrated immune cell subtypes. Full article

(This article belongs to the Special Issue Cancer Biomarkers: Recent Progress, Innovations and Future Clinical Implications)

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Review

Jump to: Research

32 pages, 965 KiB

Open AccessReview

Genomic Newborn Screening for Pediatric Cancer Predisposition Syndromes: A Holistic Approach

by BalaSubramani Gattu Linga, Sawsan G. A. A. Mohammed, Thomas Farrell, Hilal Al Rifai, Nader Al-Dewik and M. Walid Qoronfleh

Cancers 2024, 16(11), 2017; https://doi.org/10.3390/cancers16112017 - 26 May 2024

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Abstract

As next-generation sequencing (NGS) has become more widely used, germline and rare genetic variations responsible for inherited illnesses, including cancer predisposition syndromes (CPSs) that account for up to 10% of childhood malignancies, have been found. The CPSs are a group of germline genetic [...] Read more.

As next-generation sequencing (NGS) has become more widely used, germline and rare genetic variations responsible for inherited illnesses, including cancer predisposition syndromes (CPSs) that account for up to 10% of childhood malignancies, have been found. The CPSs are a group of germline genetic disorders that have been identified as risk factors for pediatric cancer development. Excluding a few “classic” CPSs, there is no agreement regarding when and how to conduct germline genetic diagnostic studies in children with cancer due to the constant evolution of knowledge in NGS technologies. Various clinical screening tools have been suggested to aid in the identification of individuals who are at greater risk, using diverse strategies and with varied outcomes. We present here an overview of the primary clinical and molecular characteristics of various CPSs and summarize the existing clinical genomics data on the prevalence of CPSs in pediatric cancer patients. Additionally, we discuss several ethical issues, challenges, limitations, cost-effectiveness, and integration of genomic newborn screening for CPSs into a healthcare system. Furthermore, we assess the effectiveness of commonly utilized decision-support tools in identifying patients who may benefit from genetic counseling and/or direct genetic testing. This investigation highlights a tailored and systematic approach utilizing medical newborn screening tools such as the genome sequencing of high-risk newborns for CPSs, which could be a practical and cost-effective strategy in pediatric cancer care. Full article

(This article belongs to the Special Issue Cancer Biomarkers: Recent Progress, Innovations and Future Clinical Implications)

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0 pages, 1840 KiB

Open AccessReview

The Role of Apolipoproteins in the Commonest Cancers: A Review

by Nour M. Darwish, Mooza Kh. Al-Hail, Youssef Mohamed, Rafif Al Saady, Sara Mohsen, Amna Zar, Layla Al-Mansoori and Shona Pedersen

Cancers 2023, 15(23), 5565; https://doi.org/10.3390/cancers15235565 - 24 Nov 2023

Cited by 1 | Viewed by 2136

Abstract

Apolipoproteins (APOs) are vital structural components of plasma lipoproteins that are involved in lipid metabolism and transport. Recent studies have reported an association between apolipoprotein dysregulation and the onset of a variety of human cancers; however, the role of certain APOs in cancer [...] Read more.

Apolipoproteins (APOs) are vital structural components of plasma lipoproteins that are involved in lipid metabolism and transport. Recent studies have reported an association between apolipoprotein dysregulation and the onset of a variety of human cancers; however, the role of certain APOs in cancer development remains unknown. Based on recent work, we hypothesize that APOs might be involved in the onset of cancer, with a focus on the most common cancers, including breast, lung, gynecological, colorectal, thyroid, gastric, pancreatic, hepatic, and prostate cancers. This review will focus on the evidence supporting this hypothesis, the mechanisms linking APOs to the onset of cancer, and the potential clinical relevance of its various inhibitors. Full article

(This article belongs to the Special Issue Cancer Biomarkers: Recent Progress, Innovations and Future Clinical Implications)

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32 pages, 1497 KiB

Open AccessReview

Unveiling a Biomarker Signature of Meningioma: The Need for a Panel of Genomic, Epigenetic, Proteomic, and RNA Biomarkers to Advance Diagnosis and Prognosis

by Reem Halabi, Fatima Dakroub, Mohammad Z. Haider, Stuti Patel, Nayef A. Amhaz, Mohammad A. Reslan, Ali H. Eid, Yehia Mechref, Nadine Darwiche, Firas Kobeissy, Ibrahim Omeis and Abdullah A. Shaito

Cancers 2023, 15(22), 5339; https://doi.org/10.3390/cancers15225339 - 9 Nov 2023

Cited by 1 | Viewed by 2242

Abstract

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas’ tremendous variability in tumor behavior and slow growth rates complicate their diagnosis [...] Read more.

Meningiomas are the most prevalent primary intracranial tumors. The majority are benign but can undergo dedifferentiation into advanced grades classified by World Health Organization (WHO) into Grades 1 to 3. Meningiomas’ tremendous variability in tumor behavior and slow growth rates complicate their diagnosis and treatment. A deeper comprehension of the molecular pathways and cellular microenvironment factors implicated in meningioma survival and pathology is needed. This review summarizes the known genetic and epigenetic aberrations involved in meningiomas, with a focus on neurofibromatosis type 2 (NF2) and non-NF2 mutations. Novel potential biomarkers for meningioma diagnosis and prognosis are also discussed, including epigenetic-, RNA-, metabolomics-, and protein-based markers. Finally, the landscape of available meningioma-specific animal models is overviewed. Use of these animal models can enable planning of adjuvant treatment, potentially assisting in pre-operative and post-operative decision making. Discovery of novel biomarkers will allow, in combination with WHO grading, more precise meningioma grading, including meningioma identification, subtype determination, and prediction of metastasis, recurrence, and response to therapy. Moreover, these biomarkers may be exploited in the development of personalized targeted therapies that can distinguish between the 15 diverse meningioma subtypes. Full article

(This article belongs to the Special Issue Cancer Biomarkers: Recent Progress, Innovations and Future Clinical Implications)

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18 pages, 1546 KiB

Open AccessReview

Krüppel-like Factor 10 as a Prognostic and Predictive Biomarker of Radiotherapy in Pancreatic Adenocarcinoma

by Yi-Chih Tsai, Min-Chieh Hsin, Rui-Jun Liu, Ting-Wei Li and Hui-Ju Ch’ang

Cancers 2023, 15(21), 5212; https://doi.org/10.3390/cancers15215212 - 30 Oct 2023

Viewed by 1132

Abstract

The prognosis of pancreatic adenocarcinoma (PDAC) remains poor, with a 5-year survival rate of 12%. Although radiotherapy is effective for the locoregional control of PDAC, it does not have survival benefits compared with systemic chemotherapy. Most patients with localized PDAC develop distant metastasis [...] Read more.

The prognosis of pancreatic adenocarcinoma (PDAC) remains poor, with a 5-year survival rate of 12%. Although radiotherapy is effective for the locoregional control of PDAC, it does not have survival benefits compared with systemic chemotherapy. Most patients with localized PDAC develop distant metastasis shortly after diagnosis. Upfront chemotherapy has been suggested so that patients with localized PDAC with early distant metastasis do not have to undergo radical local therapy. Several potential tissue markers have been identified for selecting patients who may benefit from local radiotherapy, thereby prolonging their survival. This review summarizes these biomarkers including SMAD4, which is significantly associated with PDAC failure patterns and survival. In particular, Krüppel-like factor 10 (KLF10) is an early response transcription factor of transforming growth factor (TGF)-β. Unlike TGF-β in advanced cancers, KLF10 loss in two-thirds of patients with PDAC was associated with rapid distant metastasis and radioresistance; thus, KLF10 can serve as a predictive and therapeutic marker for PDAC. For patients with resectable PDAC, a combination of KLF10 and SMAD4 expression in tumor tissues may help select those who may benefit the most from additional radiotherapy. Future trials should consider upfront systemic therapy or include molecular biomarker-enriched patients without early distant metastasis. Full article

(This article belongs to the Special Issue Cancer Biomarkers: Recent Progress, Innovations and Future Clinical Implications)

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