Editorial: Cancer Biomarkers: Molecular Insights into Diagnosis

Matteo Becatti^1*Shaoquan Zheng²Giuseppe Bronte³

• ¹Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Firenze, Firenze, Italy
• ²Breast Disease Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China
• ³Department of Translational Medicine, University of Ferrara, Ferrara, Italy; Department of Oncology, University Hospital of Ferrara, Ferrara, Italy

Cancer biomarkers represent a critical frontier in precision oncology, enabling more refined stratification of patients, earlier detection, improved therapeutic targeting, and more accurate prognostic estimation. This Research Topic assembles a collection of 14 diverse yet thematically converging articles that reflect the state-of-the-art and evolving paradigms in biomarker science across a variety of tumor types. Several studies in this collection identify gene expression drivers of tumor progression and therapy resistance, such as DAP3 in hepatocellular carcinoma, HJURP in gastric cancer, and ANTXR1 in bladder cancer. DAP3 was shown to promote tumor proliferation, invasion, and resistance to apoptosis, with a predictive model constructed based on its expression (https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1528853/full). HJURP was found to modulate chemoresistance via the MYC/TOP2A axis in gastric cancer, supporting its candidacy as a dual biomarker and therapeutic target (https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1566293/full). ANTXR1 expression correlated with stromal scores and poor prognosis in bladder cancer, positioning it as both a prognostic marker and a candidate for targeted therapy (https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1520223/full).Other contributions focus on prognostic and predictive biomarker models. A meta-analysis of over 9,000 patients demonstrated that a high glucose-to-lymphocyte ratio (GLR) is a negative prognostic factor across various solid tumors, especially hepatocellular, breast, and pancreatic cancers (https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1454393/full). In esophageal squamous cell carcinoma, machine learning identified ATF2, ALOXE3, and SLC27A5 as predictive of response to chemoradiotherapy and overall survival, integrating gene expression, immune profiles, and drug sensitivity data (https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1512715/full). Additionally, an epidemiological modeling study on lung cancer burden in BRICS nations revealed escalating trends in China and India, underscoring the importance of integrating biomarker strategies into public health policies (https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1511530/full).Innovations in diagnostic approaches also feature prominently. In colorectal cancer, immunolipid magnetic beads targeting EpCAM and vimentin enabled sensitive and specific capture of circulating tumor cells (CTCs), with a high concordance to tissue-derived mutation profiles (https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1531972/full). Plasma autoantibodies to COPT1 showed potential as early diagnostic biomarkers for non-small cell lung cancer (NSCLC), with combining IgG and IgM achieving an AUC of 0.784, further enhanced by CEA inclusion (https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1455095/full). In rectal carcinoma, diffusion-weighted MRI and ADC mapping distinguished malignancy from radiation-induced proctitis and normal tissue with near-perfect sensitivity and specificity, though not linked to prognosis (https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1464183/full).The immune microenvironment and its modulation through intrinsic tumor pathways are also explored. One study evaluated cGAS/STING pathway activation across 15 checkpoint inhibitor-treated cohorts (https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1556736/full). While STING activation correlated with improved survival in some datasets (e.g., melanoma and bladder cancer), it was paradoxically associated with poor outcomes in others (e.g., renal carcinoma), suggesting tumor-type-specific immune dynamics. This is echoed by work on circMIB1 in glioma, which functions as a competing endogenous RNA sponging miR-1290, thereby upregulating tumor suppressor genes involved in apoptosis and circadian rhythm regulation (https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1513919/full). These insights contribute to our understanding of non-coding RNAs in modulating oncogenic pathways and immunogenicity.Additional complexity is addressed in rare or diagnostically ambiguous tumors. A bioinformatic study identified overlapping gene signatures between acute myocardial infarction and non-small cell lung cancer (NSCLC). COL1A1 and PLAU were identified as key hub genes with diagnostic value. Repurposable drugs, such as zoledronic acid, emerged for connection with hub genes. These findings supported the usefulness of the protein-protein interaction network analysis to identify hub genes (https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2024.1502509/full). A case report detailed the misdiagnosis of pulmonary Ewing sarcoma as NSCLC, corrected through molecular pathology revealing an EWSR1::FLI1 fusion gene (https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2024.1449119/full). This led to a treatment shift to VDC + IE chemotherapy, surgery, and radiotherapy with excellent response, highlighting the vital role of molecular diagnostics and reference pathology centers. A comprehensive review article synthesized established and emerging biomarkers in colorectal cancer, including KRAS, BRAF, MSI, HER-2, RET, and ctDNA, providing a framework for integrating biomarkers into therapeutic algorithms and clinical trial design (https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1532924/full).Taken together, these studies underscore the multifaceted role of biomarkers in guiding diagnosis, prognosis, and decision for personalized therapy. They also highlight persistent challenges, including biomarker standardization, cross-platform validation, and accessibility in clinical settings. Yet, the collective insights affirm that the integration of omics data, computational biology, and translational research is reshaping oncology toward a more precise and patient-centered practice. This Research Topic demonstrates that continued interdisciplinary collaboration is key to unlocking the full potential of biomarker-driven oncology.Conflict of InterestThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.The authors declared that they were editorial board members of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.Author ContributionsMB: Writing – review & editing; SZ: Writing – review & editing; GB: Writing – review & editingFundingThe authors declare that no financial support was received for the research, authorship, and/or publication of this article.