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Molecular Biomarkers in Cancer and Their Applications 2.0
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Molecular Biomarkers in Cancer and Their Applications 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 5356

Special Issue Editor

Dr. Cristina Peña

E-Mail Website
Guest Editor
1. Medical Oncology Department, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Alcalá University, 28034 Madrid, Spain
2. Centro de Investigación Biomédica en Red de Cancer (CIBERONC), 28029 Madrid, Spain
Interests: tumor microenvironment; colorectal cancer; cancer-associated fibroblasts; exosomes; migration and invasion; tumor biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A molecular biomarker in cancer is a measurable indicator, including genetic variations, differences in messenger RNA (mRNA) and/or protein expression, post-translational modifications of proteins, metabolite levels, among others. A large amount of literature has demonstrated the potential of different molecular biomarkers for clinical utility. Thus, molecular biomarkers guide disease diagnostics or drug treatment in many settings. Based on their clinical use, they can be classified as diagnostic, prognostic, pharmacodynamic or predictive cancer biomarkers. Currently, the use of liquid biopsy, mainly blood or serum, to identify molecular biomarkers is showing high potential to better understand tumor heterogeneity and tumor molecular behavior in order to identify the best type of treatment.

This Special Issue welcomes original research and review papers. Potential topics include, but are not limited to, the following:

  • Determination of new molecular biomarker for patient classification (diagnostic) and for patient survival prediction (prognostic).
  • Manuscripts related to molecular biomarkers for treatment efficacy or toxicity (pharmacodynamics and predictive biomarkers).
  • Application of molecular biomarkers in the development of novel cancer therapies.
  • Large-scale genomic and proteomic analysis for molecular biomarker identification.
  • Identification of pathway-specific biomarkers to consider the efficacy of targeted cancer treatments.
  • Machine learning studies from large data sets to identify new cancer-related molecular biomarkers.
  • Potential application of cancer molecular biomarkers in liquid biopsies.

Dr. Cristina Peña
Guest Editor

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

  • molecular biomarker
  • liquid biopsy molecular biomarker
  • diagnostic predictive molecular biomarkers
  • prognostic molecular biomarkers
  • pharmacodynamics molecular biomarkers
  • predictive molecular biomarkers

Published Papers (5 papers)

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Research

13 pages, 1044 KiB  
Article
Prognostic Value of Circulating Cell-Free DNA Concentration and Neutrophil-to-Lymphocyte Ratio in Patients with Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study
by Bianca Varzaru, Razvan Andrei Iacob, Stefania Bunduc, Ioana Manea, Andrei Sorop, Andreea Spiridon, Raluca Chelaru, Adina Croitoru, Mihaela Topala, Gabriel Becheanu, Mona Dumbrava, Simona Dima, Irinel Popescu and Cristian Gheorghe
Int. J. Mol. Sci. 2024, 25(5), 2854; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25052854 - 01 Mar 2024
Viewed by 625
Abstract
Circulating cell-free DNA (ccfDNA) quantity correlates with the clinical characteristics and prognosis of various cancer types. We investigated whether ccfDNA levels and the neutrophil-to-lymphocyte ratio (NLR) have prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral blood was collected from 82 patients [...] Read more.
Circulating cell-free DNA (ccfDNA) quantity correlates with the clinical characteristics and prognosis of various cancer types. We investigated whether ccfDNA levels and the neutrophil-to-lymphocyte ratio (NLR) have prognostic value in patients with pancreatic ductal adenocarcinoma (PDAC). Peripheral blood was collected from 82 patients with PDAC prior to any diagnostic procedure or the administration of chemotherapy. Plasma DNA was isolated, and ccfDNA concentration and NLR were determined. We found that ccfDNA levels were correlated with age and tumor burden. Moreover, higher values of NLR (≥3.31) were linked with worse overall survival (OS) (4 vs. 10 months; log rank p = 0.011), and an elevated ccfDNA concentration (≥25.79 ng/mL) was strongly associated with shorter OS (4 vs. 8 months; log rank p = 0.009). According to the results of the multivariable Cox regression analysis, the baseline concentration of ccfDNA was an independent prognostic factor for OS (HR 0.45, 95% CI 0.21–0.97, p = 0.041). Furthermore, the combination of ccfDNA levels with NLR greatly enhanced the prognostic accuracy of PDAC patients. Our study demonstrates that ccfDNA concentration and NLR are independent predictors of survival in PDAC. Subsequent studies should validate this combination as a prognostic indicator in PDAC patients and assess its utility for guiding therapeutic decisions. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancer and Their Applications 2.0)
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13 pages, 2223 KiB  
Article
uPAR (PLAUR) Marks Two Intra-Tumoral Subtypes of Glioblastoma: Insights from Single-Cell RNA Sequencing
by Yue He, Kristina B. V. Døssing, Maria Rossing, Frederik Otzen Bagger and Andreas Kjaer
Int. J. Mol. Sci. 2024, 25(4), 1998; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25041998 - 07 Feb 2024
Viewed by 774
Abstract
Urokinase plasminogen activator receptor (uPAR) encoded by the PLAUR gene is known as a clinical marker for cell invasiveness in glioblastoma multiforme (GBM). It is additionally implicated in various processes, including angiogenesis and inflammation within the tumor microenvironment. However, there has not been [...] Read more.
Urokinase plasminogen activator receptor (uPAR) encoded by the PLAUR gene is known as a clinical marker for cell invasiveness in glioblastoma multiforme (GBM). It is additionally implicated in various processes, including angiogenesis and inflammation within the tumor microenvironment. However, there has not been a comprehensive study that depicts the overall functions and molecular cooperators of PLAUR with respect to intra-tumoral subtypes of GBM. Using single-cell RNA sequencing data from 37 GBM patients, we identified PLAUR as a marker gene for two distinct subtypes in GBM. One subtype is featured by inflammatory activities and the other subtype is marked by ECM remodeling processes. Using the whole-transcriptome data from single cells, we are able to uncover the molecular cooperators of PLAUR for both subtypes without presuming biological pathways. Two protein networks comprise the molecular context of PLAUR, with each of the two subtypes characterized by a different dominant network. We concluded that targeting PLAUR directly influences the mechanisms represented by these two protein networks, regardless of the subtype of the targeted cell. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancer and Their Applications 2.0)
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22 pages, 6388 KiB  
Article
Bioinformatics and Experimental Validation for Identifying Biomarkers Associated with AMG510 (Sotorasib) Resistance in KRASG12C-Mutated Lung Adenocarcinoma
by Peng Lin, Wei Cheng, Xin Qi, Pinglu Zhang, Jianshe Xiong and Jing Li
Int. J. Mol. Sci. 2024, 25(3), 1555; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25031555 - 26 Jan 2024
Viewed by 994
Abstract
The Kirsten rat sarcoma viral oncogene homolog (KRAS)G12C mutation is prevalent in lung adenocarcinoma (LUAD), driving tumor progression and indicating a poor prognosis. While the FDA-approved AMG510 (Sotorasib) initially demonstrated efficacy in treating KRASG12C-mutated LUAD, resistance emerged within months. Data [...] Read more.
The Kirsten rat sarcoma viral oncogene homolog (KRAS)G12C mutation is prevalent in lung adenocarcinoma (LUAD), driving tumor progression and indicating a poor prognosis. While the FDA-approved AMG510 (Sotorasib) initially demonstrated efficacy in treating KRASG12C-mutated LUAD, resistance emerged within months. Data from AMG510 treatment-resistant LUAD (GSE204753) and single-cell datasets (GSE149655) were analyzed. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were used to explore enriched signaling pathways, nomogram models were constructed, and transcription factors predicting resistance biomarkers were predicted. CIBERSORT identified immune cell subpopulations, and their association with resistance biomarkers was assessed through single-cell analysis. AMG510-resistant LUAD cells (H358-AR) were constructed, and proliferative changes were evaluated using a CCK-8 assay. Key molecules for AMG510 resistance, including SLC2A1, TLE1, FAM83A, HMGA2, FBXO44, and MTRNR2L12, were recognized. These molecules impacted multiple signaling pathways and the tumor microenvironment and were co-regulated by various transcription factors. Single-cell analysis revealed a dampening effect on immune cell function, with associations with programmed cell death ligand 1 (PDL1) expression, cytokine factors, and failure factors. The findings indicate that these newly identified biomarkers are linked to the abnormal expression of PDL1 and have the potential to induce resistance through immunosuppression. These results highlight the need for further research and therapeutic intervention to address this issue effectively. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancer and Their Applications 2.0)
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13 pages, 1713 KiB  
Article
Mitogen-Activated Protein Kinase 15 Is a New Predictive Biomarker and Potential Therapeutic Target for Ovarian Cancer
by Qiu-Hua Zhong, Andy T. Y. Lau and Yan-Ming Xu
Int. J. Mol. Sci. 2024, 25(1), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25010109 - 20 Dec 2023
Cited by 1 | Viewed by 970
Abstract
Mitogen-activated protein kinase 15 (MAPK15) has been reported to be associated with several cancers. This study aimed to explore for the first time on the relationship between MAPK15 expression and cancer progression/drug responsiveness in ovarian carcinoma. To this end, MAPK15 expression level was [...] Read more.
Mitogen-activated protein kinase 15 (MAPK15) has been reported to be associated with several cancers. This study aimed to explore for the first time on the relationship between MAPK15 expression and cancer progression/drug responsiveness in ovarian carcinoma. To this end, MAPK15 expression level was examined by immunohistochemistry (IHC) staining of an ovarian tissue array (10 normal and 70 malignant samples). Drug sensitivity of ovarian cancer cell lines (including OVCAR3 and SKOV3) was measured by MTS assay. The modulation of MAPK15 expression in OVCAR3 and SKOV3 was verified by immunoblot and real-time PCR analyses. The prognostic value of MAPK15 in ovarian cancer patients was assessed using the Kaplan-Meier Plotter database and Gene Expression Omnibus (GEO) datasets. The IHC results showed that MAPK15 expression was negatively associated with tumor grade, TNM stage, tumor size, and regional lymph node metastasis of ovarian carcinoma. Importantly, overexpressing MAPK15 increased cisplatin toxicity in ovarian carcinoma cells and online database analysis indicated that patients with high MAPK15 expression had favorable prognosis with/without chemotherapy. Taken together, our results indicate that a decreased MAPK15 expression is associated with advanced-stage ovarian cancer and unfavorable survival outcomes. MAPK15 may be a new biomarker for ovarian cancer, and the encouraging therapeutic strategy would be found by combining the regulation of MAPK15 expression. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancer and Their Applications 2.0)
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15 pages, 2050 KiB  
Article
SFPQ and Its Isoform as Potential Biomarker for Non-Small-Cell Lung Cancer
by Libang Yang, Adam Gilbertsen, Blake Jacobson, Jenny Pham, Naomi Fujioka, Craig A. Henke and Robert A. Kratzke
Int. J. Mol. Sci. 2023, 24(15), 12500; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241512500 - 06 Aug 2023
Viewed by 1633
Abstract
Cancer markers are measurable molecules in the blood or tissue that are produced by tumor cells or immune cells in response to cancer progression. They play an important role in clinical diagnosis, prognosis, and anti-drug monitoring. Although DNA, RNA, and even physical images [...] Read more.
Cancer markers are measurable molecules in the blood or tissue that are produced by tumor cells or immune cells in response to cancer progression. They play an important role in clinical diagnosis, prognosis, and anti-drug monitoring. Although DNA, RNA, and even physical images have been used, proteins continue to be the most common marker. There are currently no specific markers for lung cancer. Metastatic lung cancer, particularly non-small-cell lung cancer (NSCLC), is one of the most common causes of death. SFPQ, YY1, RTN4, RICTOR, LARP6, and HELLS are expressed at higher levels in cells from NSCLC than in control or cells from inflammatory diseases. SFPQ shows the most difference between the three cell types. Furthermore, the cytoplasmic isoform of SFPQ is only found in advanced cancers. We have developed ELISAs to detect SFPQ and the long and short isoforms. Evidence has shown that the short isoform exists primarily in cancers. Furthermore, immunocytometry studies and IHC analysis have revealed that SFPQ levels are consistent with ELISA results. In addition, enhanced DNA methylation in the SFPQ gene may facilitate the SFPQ expression differences between control and cancer cells. Considering this, elevated SFPQ level and the isoform location could serve as a cancer diagnostic and prognostic marker. Full article
(This article belongs to the Special Issue Molecular Biomarkers in Cancer and Their Applications 2.0)
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