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Molecular Biomarkers in Cancers: Advances and Challenges, 2nd Edition
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Molecular Biomarkers in Cancers: Advances and Challenges, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 January 2026 | Viewed by 7485

Special Issue Editors

Dr. Paramjit S. Tappia

E-Mail Website
Guest Editor
Asper Clinical Research Institute, St. Boniface Hospital, Winnipeg, MB R2H 2A6, Canada
Interests: cardiovascular disease; diabetes; nutrition; early-stage lung cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Bram Ramjiawan

E-Mail Website
Guest Editor
Asper Clinical Research Institute, St. Boniface Hospital, Department of Pharmacology and Therapeutics Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada
Interests: oncology; research; pharmacology; ethics; cancer; cardiology; diabetes; innovation; regulatory
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

There are several diagnostic techniques and procedures currently used for the diagnosis of cancer. Although computed tomography, magnetic resonance imaging, and ultrasound technology are considered gold-standard procedures for the detection of cancer, they are often associated with an undesirably high level of false positives, are also expensive, present accessibility issues, and involve exposure to ionizing radiation. Most of the non-imaging techniques for cancer detection are employed to corroborate biomarkers that are overexpressed in cancer cells. A number of assays have been developed to measure protein, microRNA, circulating DNA, and methylated DNA biomarkers in the blood for the detection of cancer. In addition, biopsies for molecular and biomarker diagnosis have also been utilized, but they are invasive and uncomfortable for patients. While these approaches have clinical value that is more specific to late-stage cancer, they have limited value for the early detection of cancer. Accordingly, the identification of highly specific and highly selective novel molecular biomarkers for cancer diagnosis that also provide information on staging of the disease is warranted. In this Special Issue, we describe the pros and cons of current molecular approaches used in the diagnosis of cancer, as well as the technical advances in and challenges for establishing molecular biomarkers for determining the risk, detection, and progression of cancer.

Dr. Paramjit S. Tappia
Dr. Bram Ramjiawan
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • cancer staging
  • diagnostic tools
  • novel biomarkers
  • proteomics
  • molecular markers
  • metabolic profiling
  • prognostic value

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Related Special Issue

Published Papers (5 papers)

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Research

16 pages, 2581 KB  
Article
Candidate Transcript Panel in Semen Extracellular Vesicles Can Improve Prediction of Aggressiveness of Prostate Cancer
by Adriana Ferre-Giraldo, Manel Castells, Alicia Madurga, Ariadna Arbiol-Roca, Maurizio de Rocco-Ponce, Lluís Bassas, Francesc Vigués and Sara Larriba
Int. J. Mol. Sci. 2025, 26(19), 9562; https://doi.org/10.3390/ijms26199562 - 30 Sep 2025
Viewed by 402
Abstract
The need for prostate cancer (PCa)-specific biomarkers that enable more accurate detection of the disease and better prediction of tumor aggressiveness remains ongoing due to the low cancer specificity of PSA screening. Several potential mRNA markers for diagnosing PCa, in tissue and urine, [...] Read more.
The need for prostate cancer (PCa)-specific biomarkers that enable more accurate detection of the disease and better prediction of tumor aggressiveness remains ongoing due to the low cancer specificity of PSA screening. Several potential mRNA markers for diagnosing PCa, in tissue and urine, have been reported in the literature. In this study, we aim to explore the potential of selected prostate-specific molecules and transcripts contained in small extracellular vesicles (sEVs) in semen to predict PCa risk reclassification for patients with moderately elevated PSA levels—a clinical scenario where identifying truly non-invasive biomarkers is especially critical. RT-qPCR analysis in semen sEVs successfully showed differential expression of KLK3 and PCA3 genes between PCa and healthy controls, whereas CREB3L4, CCNQ and DUSP23 levels were related to the severity or degree of PCa affectation. Our findings also present strong evidence that classifiers based on combined long transcript levels in semen sEVs serve as effective biomarkers. They can be used alone or in combination with blood PSA and/or semen citric acid levels to improve the diagnosis of PCa and assess its severity and disease progression with high accuracy. This strategy would allow a more comprehensive assessment, increase prognostic accuracy, and facilitate accurate clinical decision-making in the management of PCa. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges, 2nd Edition)
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13 pages, 3424 KB  
Article
Identification of miRNA/FGFR2 Axis in Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors
by Elisabetta Cavalcanti, Viviana Scalavino, Leonardo Vincenti, Emanuele Piccinno, Lucia De Marinis, Raffaele Armentano and Grazia Serino
Int. J. Mol. Sci. 2025, 26(15), 7232; https://doi.org/10.3390/ijms26157232 - 26 Jul 2025
Viewed by 631
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors with different clinical and biological characteristics. Ki-67 staining and mitotic counts are the most commonly used prognostic markers, but these methods are time-consuming and lack reproducibility, highlighting the need for innovative approaches that improve histological evaluation [...] Read more.
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors with different clinical and biological characteristics. Ki-67 staining and mitotic counts are the most commonly used prognostic markers, but these methods are time-consuming and lack reproducibility, highlighting the need for innovative approaches that improve histological evaluation and prognosis. In our previous study, we observed that the microRNA (miRNA) expression profile of GEP-NENs correlates with the three grades of GEP-NENs. This study aimed to characterize a group of miRNAs that discriminate well-differentiated GEP-NENs grading 1 (G1) and grading (G2). Fifty formalin-fixed and paraffin-embedded tissue specimens from well-differentiated GEP-NENs G1 and G2 tissues were used for this study. The expression levels of 21 miRNAs were examined using qRT-PCR, while FGFR2 and FGF1 protein expression were evaluated through immunohistochemistry (IHC). We identified four miRNAs (hsa-miR-133, hsa-miR-150-5p, hsa-miR-143-3p and hsa-miR-378a-3p) that are downregulated in G2 GEP-NENs compared to G1. Bioinformatic analysis revealed that these miRNAs play a key role in modulating the FGF/FGFR signaling pathway. Consistent with this observation, we found that fibroblast growth factor receptor 2 (FGFR2) expression is markedly higher in G2 NENs patients, whereas its expression remains low in G1 NENs. Our findings highlight the potential use of miRNAs to confirm the histological evaluation of GEP-NENs by employing them as biomarkers for improving histological evaluation and tumor classification. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges, 2nd Edition)
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19 pages, 4078 KB  
Article
Functional Role of NOXA in Hypoxia-Mediated PD-L1 Inhibitor Response in Hepatocellular Carcinoma
by Mohan Huang, Tian Lan, Xinyue Chen, Rong Chen, Xin Ding, William Chi-Shing Tai, Sze Chuen-Cesar Wong and Lawrence Wing-Chi Chan
Int. J. Mol. Sci. 2025, 26(10), 4766; https://doi.org/10.3390/ijms26104766 - 16 May 2025
Viewed by 998
Abstract
Hypoxia is a crucial characteristic of hepatocellular carcinoma (HCC) and contributes to immune resistance by upregulating PD-L1 and recruiting immunosuppressive cells. However, the molecular mechanisms of hypoxia-induced immunotherapy resistance are still unclear. The hypoxia-related immunotherapy response (IRH) genes were identified and used to [...] Read more.
Hypoxia is a crucial characteristic of hepatocellular carcinoma (HCC) and contributes to immune resistance by upregulating PD-L1 and recruiting immunosuppressive cells. However, the molecular mechanisms of hypoxia-induced immunotherapy resistance are still unclear. The hypoxia-related immunotherapy response (IRH) genes were identified and used to develop a hypoxia risk score model to predict patient survival. The model was validated using GSE233802 and EGAD00001008128 datasets. The hypoxia risk score model including NOXA effectively stratified patients based on risk and demonstrated excellent survival predictive ability (p = 0.0236). A hypoxia-induced drug-resistant (HepG2-R) cell line was established by co-culturing HepG2 cells with Jurkat T cells under CoCl2-induced hypoxia and PD-L1 inhibitor administration. Prolonged exposure to hypoxia (48 h) in HepG2 cells significantly led to the increased hypoxia risk score (p < 0.02). The establishment of the HepG2-R cell line showed that prolonged hypoxia reduced cancer cell apoptosis, which implies potential treatment resistance. The effect of NOXA knockdown on the apoptosis of HepG2-R cells under the same co-culture conditions was examined. Under hypoxia and PD-L1 inhibitor treatment, NOXA knockdown increased the survival rate of HepG2-R cells and reduced early and late apoptosis. This indicates that NOXA plays a crucial role in apoptosis regulation and immune response in hypoxic tumors. NOXA knockdown significantly reduces apoptosis in immunotherapy-resistant cells induced by hypoxia. These findings provide important evidence that targeting NOXA may enhance immunotherapy efficacy and help overcome treatment resistance in HCC, highlighting its potential as a therapeutic target. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges, 2nd Edition)
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15 pages, 7295 KB  
Article
Prognostic Significance of Overexpression of BCL9 and TPX2 in High-Grade Clear Cell Renal Cell Carcinoma: Prognostic Markers for Metastasis and Survival
by Michał Kasperczak, Iga Kołodziejczak-Guglas, Filip Kasperczak, Maciej Wiznerowicz and Andrzej Antczak
Int. J. Mol. Sci. 2025, 26(9), 4114; https://doi.org/10.3390/ijms26094114 - 26 Apr 2025
Viewed by 2867
Abstract
Clear-cell renal cell carcinoma (ccRCC) is a kidney cancer associated with poor prognosis and limited treatment options. Identifying new prognostic markers is crucial. This study investigates the potential of BCL9 and TPX2, two proteins involved in cancer progression, to predict patient outcomes This [...] Read more.
Clear-cell renal cell carcinoma (ccRCC) is a kidney cancer associated with poor prognosis and limited treatment options. Identifying new prognostic markers is crucial. This study investigates the potential of BCL9 and TPX2, two proteins involved in cancer progression, to predict patient outcomes This study analyzed protein abundance data from the CPTAC cohort (110 ccRCC and 84 NAT samples) using LC-MS/MS. BCL9 and TPX2 were validated via immunohistochemistry (IHC) in an independent cohort (52 ccRCC samples). Patients were stratified into high- and low-expression groups based on IHC scores. Survival analyses were conducted, and Reactome pathway enrichment analysis was performed. BCL9 and TPX2 were significantly upregulated in ccRCC compared to NAT. In the validation cohort, high BCL9 levels were associated with shorter progression-free survival (PFS) but not OS, while high TPX2 levels correlated with shorter overall survival (OS) but not PFS. Pathway analysis linked BCL9 to Wnt signaling and TPX2 to cell cycle regulation. Elevated BCL9 and TPX2 are associated with poor prognosis in ccRCC. These proteins are potential prognostic markers and therapeutic targets. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges, 2nd Edition)
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24 pages, 5008 KB  
Article
Semen sEV tRF-Based Models Increase Non-Invasive Prediction Accuracy of Clinically Significant Prostate Cancer among Patients with Moderately Altered PSA Levels
by Adriana Ferre-Giraldo, Manel Castells, José Francisco Sánchez-Herrero, Olga López-Rodrigo, Maurizio de Rocco-Ponce, Lluís Bassas, Francesc Vigués, Lauro Sumoy and Sara Larriba
Int. J. Mol. Sci. 2024, 25(18), 10122; https://doi.org/10.3390/ijms251810122 - 20 Sep 2024
Cited by 5 | Viewed by 2029
Abstract
PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) [...] Read more.
PSA screening has led to an over-diagnosis of prostate cancer (PCa) and unnecessary biopsies of benign conditions due to its low cancer specificity. Consequently, more accurate, preferentially non-invasive, tests are needed. We aim to evaluate the potential of semen sEV (small extracellular vesicles) tsRNAs (tRNA-derived small RNAs) as PCa indicators. Initially, following a literature review in the OncotRF database and high-throughput small RNA-sequencing studies in PCa tissue together with the sncRNA profile in semen sEVs, we selected four candidate 5′tRF tsRNAs for validation as PCa biomarkers. RT-qPCR analysis in semen sEVs from men with moderately elevated serum PSA levels successfully shows that the differential expression of the four tRFs between PCa and healthy control groups can be detected in a non-invasive manner. The combined model incorporating PSA and specific tRFs (5′-tRNA-Glu-TTC-9-1_L30 and 5′-tRNA-Val-CAC-3-1_L30) achieved high predictive accuracy in identifying samples with a Gleason score ≥ 7 and staging disease beyond IIA, supporting that the 5′tRF fingerprint in semen sEV can improve the PSA predictive value to discriminate between malignant and indolent prostate conditions. The in silico study allowed us to map target genes for the four 5′tRFs possibly involved in PCa. Our findings highlight the synergistic use of multiple biomarkers as an efficient approach to improve PCa screening and prognosis. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancers: Advances and Challenges, 2nd Edition)
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