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Biomarker Discovery and Validation for Precision Oncology
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Biomarker Discovery and Validation for Precision Oncology

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: 30 June 2025 | Viewed by 1541

Special Issue Editor

Dr. Luís Lima

E-Mail Website
Guest Editor
Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
Interests: oncology; biomedical science; genotyping; cancer research; biomarker discovery and validation; bladder cancer; liquid biopsies; CTC identification; gastrointestinal cancer; colorectal screening; fecal biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The integration of biomarkers into precision oncology is revolutionizing cancer care by enabling more accurate screening, diagnosis, and personalized treatment strategies.

This Special Issue, entitled "Biomarker Discovery and Validation for Precision Oncology", aims to highlight cutting-edge research and advancements in the discovery, development, and clinical validation of biomarkers across diverse cancer types, showcasing innovative research and its translational potential.

We welcome the submission of original research, reviews, and short communications focusing on a broad range of topics, including, but not limited to, the following:

  • Biomarker discovery and validation for cancer screening and diagnostics.
  • Precision medicine approaches in oncology, including targeted therapies and immunotherapies.
  • Non-invasive and liquid biopsy approaches, including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), extracellular vesicles, and omics approaches.
  • Development of new tools, technologies, and improved models to enhance biomarker research.
  • Multi-omics integration and novel methodologies in biomarker development.
  • Clinical implementation and challenges in regulatory approval of oncology biomarkers.

This Special Issue seeks to provide a platform for interdisciplinary discussions, advancing our understanding of how biomarkers can shape the future of cancer care. We encourage submissions from researchers, clinicians, and industry professionals that contribute to the growing body of knowledge in precision oncology.

Dr. Luís Lima
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

  • biomarker discovery
  • biomarker validation
  • precision oncology
  • cancer screening
  • cancer diagnostics
  • liquid biopsy
  • multi-omics integration
  • targeted therapies
  • immunotherapy biomarkers
  • translational cancer research

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Related Special Issues

Published Papers (4 papers)

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Research

25 pages, 2855 KiB  
Article
Glycomics and Glycoproteomics Reveal Distinct Oligomannose Carriers Across Bladder Cancer Stages
by Marta Relvas-Santos, Dylan Ferreira, Andreia Brandão, Luis Pedro Afonso, Lúcio Lara Santos, André M. N. Silva and José Alexandre Ferreira
Int. J. Mol. Sci. 2025, 26(10), 4891; https://doi.org/10.3390/ijms26104891 - 20 May 2025
Viewed by 241
Abstract
Aberrant glycosylation is a hallmark of cancer, offering opportunities to enhance clinical decision-making and enable precise targeting of cancer cells. Nevertheless, alterations in the bladder urothelial carcinoma (BLCA) N-glycome remain poorly characterized. Here, we used in situ N-deglycosylation and mass spectrometry, [...] Read more.
Aberrant glycosylation is a hallmark of cancer, offering opportunities to enhance clinical decision-making and enable precise targeting of cancer cells. Nevertheless, alterations in the bladder urothelial carcinoma (BLCA) N-glycome remain poorly characterized. Here, we used in situ N-deglycosylation and mass spectrometry, revealing a marked enrichment of oligomannose-type N-glycans in non-invasive Ta tumors, which diminished with disease progression. A complementary analysis of The Cancer Genome Atlas (TCGA) transcriptomic data revealed downregulation of the key mannosidases in BLCA, suggesting a mechanistic basis for oligomannose accumulation, though this requires further validation. Then, targeted glycoproteomic profiling identified potential stage-specific carriers of oligomannoses. Exploratory functional annotation suggests stage-dependent differences among detected glycoproteins, ranging from metabolic regulation in Ta tumors to oxidative stress adaptation in muscle-invasive disease, highlighting glycosylation’s contribution to tumor progression. Furthermore, myeloperoxidase (MPO) was enriched in more aggressive stages. Spatial validation confirmed MPO overexpression in tumor-infiltrating immune cells and its correlation with oligomannose content. Importantly, high MPO expression combined with low mannosidase levels was linked to poor survival, suggesting biological relevance. This study suggests a dynamic, stage-specific N-glycome in BLCA and identifies oligomannose-bearing glycoproteins as exploratory leads for biomarker and therapeutic target discovery, providing a N-glycomic resource for further investigation towards glycan-based precision oncology. Full article
(This article belongs to the Special Issue Biomarker Discovery and Validation for Precision Oncology)
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12 pages, 6355 KiB  
Article
Soft-Tissue Sarcomas—A Correlation Among Tumor Margin Infiltration, Immunological Markers, and Survival Rate
by Bogdan Șerban, Adrian Cursaru, Sergiu Iordache, Mihai Costache, Bogdan Cretu, Adrian Dumitru and Catalin Cirstoiu
Int. J. Mol. Sci. 2025, 26(9), 4363; https://doi.org/10.3390/ijms26094363 - 3 May 2025
Viewed by 314
Abstract
Early and appropriate diagnosis of soft-tissue sarcomas (STSs) is hampered by their relatively low prevalence and sometimes unusual clinical appearance. It takes a comprehensive diagnostic work-up to differentiate between different types of soft-tissue sarcomas. Determining tumor margins by preoperative imaging is important, especially [...] Read more.
Early and appropriate diagnosis of soft-tissue sarcomas (STSs) is hampered by their relatively low prevalence and sometimes unusual clinical appearance. It takes a comprehensive diagnostic work-up to differentiate between different types of soft-tissue sarcomas. Determining tumor margins by preoperative imaging is important, especially in order to preserve the affected limb and improve quality of life. Misjudgment of tumor margins may increase or decrease the stage of soft-tissue sarcoma and thus influence the patient’s prognosis. The applicability of conventional MRI alone for determining the tumor margin is limited. Additional information regarding the peritumoral tissue, particularly at the cellular level, can be obtained via diffusion-weighted imaging (DWI). However, there are not many publications on employing DWI to evaluate tumor margin infiltration in soft-tissue sarcoma patients. Because the immune system plays a variety of roles during oncogenesis, it can occasionally be difficult to distinguish between tumor invasion and the presence of a reactive inflammatory infiltrate. Clarifying the predictive importance of lymphocyte infiltration in soft-tissue sarcomas was the goal of this investigation. We examined the correlations between expression of CD4, CD8, and CD34 and tumor margin infiltration observed on a DWI sequence. CD4, CD8, and CD34 marker positivity was linked to soft-tissue sarcomas that were less aggressive and did not invade the tumor margins, indicating a higher survival percentage for these individuals. Full article
(This article belongs to the Special Issue Biomarker Discovery and Validation for Precision Oncology)
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15 pages, 5442 KiB  
Article
Identifying Aberrant 1CM-Related Pathways by Multi-Omics Analysis and Validating Tumor Inhibitory Effect of One-Carbon Donor Betaine in Gastric Cancer
by Jie Li, Huan Liu, Panpan Yang, Feng Zhu, Fei Shen and Geyu Liang
Int. J. Mol. Sci. 2025, 26(8), 3841; https://doi.org/10.3390/ijms26083841 - 18 Apr 2025
Viewed by 279
Abstract
Metabolic reprogramming, a well-established hallmark of gastric carcinogenesis, has been implicated in driving tumor progression. Nevertheless, the precise mechanisms through which these metabolic alterations orchestrate gastric cancer (GC) pathogenesis remain incompletely elucidated. We conducted metabolomic analyses of plasma samples obtained from 334 patients [...] Read more.
Metabolic reprogramming, a well-established hallmark of gastric carcinogenesis, has been implicated in driving tumor progression. Nevertheless, the precise mechanisms through which these metabolic alterations orchestrate gastric cancer (GC) pathogenesis remain incompletely elucidated. We conducted metabolomic analyses of plasma samples obtained from 334 patients with GC and healthy individuals to identify differential metabolites and metabolic pathways. Transcriptome sequencing was conducted on six pairs of tissues, and a joint analysis of the transcriptome and metabolome was performed. Single-cell sequencing data were acquired and co-analyzed with metabolomics to investigate metabolic abnormalities at the single-cell level. Finally, four representative metabolites selected using Random Forest analysis were subjected to cellular experiments to elucidate the mechanisms through which these metabolites exert their effects. Metabolomic analyses revealed that serine and glycine metabolism, glycolysis, and glutamate metabolism were significantly altered in GC, suggesting that one-carbon metabolism (1CM)-related pathways are aberrantly activated. A combined analysis of the transcriptome, single-cell transcriptome, and metabolomics indicated that pathways related to oxidative phosphorylation, nucleotide metabolism, and amino acid metabolism in epithelial cells were altered in GC. Cellular experiments demonstrated that the one-carbon donor metabolite betaine could inhibit the activity, invasion, and migration of GC cells while activating the phosphorylation of AMPKα. In conclusion, the 1CM-related pathway and the metabolite betaine play significant roles in GC, and the mechanisms through which the one-carbon donor betaine influences GC warrant further investigation. Full article
(This article belongs to the Special Issue Biomarker Discovery and Validation for Precision Oncology)
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10 pages, 942 KiB  
Communication
Advancing Non-Invasive Colorectal Cancer Screening: Exploring the Potential of Monoclonal Antibody L2A5
by Renato Caldevilla, Mariana Eiras, Daniela A. R. Santos, João Almeida, Beatriz Oliveira, Susana Loureiro, Janine Soares, Miguel Gonzalez-Santos, Nuno Ramos, Paula A. Videira, Lúcio Lara Santos, Mário Dinis-Ribeiro and Luís Lima
Int. J. Mol. Sci. 2025, 26(7), 3070; https://doi.org/10.3390/ijms26073070 - 27 Mar 2025
Viewed by 423
Abstract
Early detection of colorectal cancer (CRC) significantly improves overall prognosis and increases 5-year survival rates up to 90%. Current non-invasive screening methods for CRC, such as the Faecal Immunohistochemical Test (FIT), have some drawbacks, namely, low sensitivity and a high false-positive rate. The [...] Read more.
Early detection of colorectal cancer (CRC) significantly improves overall prognosis and increases 5-year survival rates up to 90%. Current non-invasive screening methods for CRC, such as the Faecal Immunohistochemical Test (FIT), have some drawbacks, namely, low sensitivity and a high false-positive rate. The Sialyl-Tn (STn) antigen, frequently expressed in pre-malignant lesions and adenocarcinomas, has been shown to be detected by the novel monoclonal antibody L2A5. In this study, we explored the potential of L2A5 as a non-invasive CRC screening method in an attempt to overcome current limitations. The subjects were categorised into four groups based on colonoscopy findings: no lesion (NL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and colorectal cancer (CRC). Slot blot analysis using the L2A5 antibody was performed on stool samples from 95 colonoscopy patients. Our findings showed a differential STn expression between the different clinical groups, evidencing excellent discrimination between NL and CRC (AUC, 0.8252; 95% CI: 0.6983–0.9521; sensitivity, 70%). Moreover, moderate discrimination between the NL+LGD and HGD+CRC groups was discerned (AUC, 0.7766; 95% CI: 0.6792–0.8740; sensitivity, 58%). These findings support the application of L2A5 as a tool for detecting STn, allowing for the identification of advanced lesions in non-invasive CRC screening. Full article
(This article belongs to the Special Issue Biomarker Discovery and Validation for Precision Oncology)
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