bims-tumhet 2025-05-04 papers

Biochim Biophys Acta Rev Cancer. 2025 Apr 30. pii: S0304-419X(25)00079-4. [Epub ahead of print] 189337

RNA methylation: A new promising biomaker in cancer liquid biopsy.

Chenxin Xu, Xin Xu, Yiwen Huang, Shuang Shang, Lifang Ma.

RNA methylation is a vital epigenetic modification that regulates gene expression by influencing RNA processes such as transcription, degradation, translation, and transport. Aberrant methylation, including modifications like m6A, m5C, m1A, m7G, and m3C, is closely linked to tumorigenesis and progression. Liquid biopsy, a non-invasive technique analyzing tumor markers in body fluids, offers significant potential for early diagnosis and dynamic monitoring. In this context, RNA methylation, due to its tumor-specific properties, is emerging as a valuable marker. However, significant challenges remain in its clinical application. This review explores the roles of RNA methylation in cancer, recent advances in detection technologies, and its potential as a liquid biopsy marker in tumor management. It highlights its promising applications in cancer diagnosis, prognosis, and personalized treatment in the era of precision oncology.

Keywords: Biomarker; Liquid biopsy; Molecular diagnostic techniques; RNA methylation; cancer

DOI: https://doi.org/10.1016/j.bbcan.2025.189337

Nat Rev Genet. 2025 Apr 25.

Advances in single-cell DNA sequencing enable insights into human somatic mosaicism.

Diane D Shao, Andrea J Kriz, Daniel A Snellings, Zinan Zhou, Yifan Zhao, Liz Enyenihi, Christopher Walsh.

DNA sequencing from bulk or clonal human tissues has shown that genetic mosaicism is common and contributes to both cancer and non-cancerous disorders. However, single-cell resolution is required to understand the full genetic heterogeneity that exists within a tissue and the mechanisms that lead to somatic mosaicism. Single-cell DNA-sequencing technologies have traditionally trailed behind those of single-cell transcriptomics and epigenomics, largely because most applications require whole-genome amplification before costly whole-genome sequencing. Now, recent technological and computational advances are enabling the use of single-cell DNA sequencing to tackle previously intractable problems, such as delineating the genetic landscape of tissues with complex clonal patterns, of samples where cellular material is scarce and of non-cycling, postmitotic cells. Single-cell genomes are also revealing the mutational patterns that arise from biological processes or disease states, and have made it possible to track cell lineage in human tissues. These advances in our understanding of tissue biology and our ability to identify disease mechanisms will ultimately transform how disease is diagnosed and monitored.

DOI: https://doi.org/10.1038/s41576-025-00832-3

NPJ Precis Oncol. 2025 Apr 25. 9(1): 120

The dynamic immune behavior of primary and metastatic ovarian carcinoma.

Patients with high-grade serous ovarian carcinoma (HGSC) are usually diagnosed with advanced-stage disease, and the tumors often have immunosuppressive characteristics. Together, these factors are important for disease progression, drug resistance, and mortality. In this study, we used a combination of single-cell sequencing and spatial transcriptomics to identify the molecular mechanisms that lead to immunosuppression in HGSC. Primary tumors consistently showed a more active immune microenvironment than did omental tumors. In addition, we found that untreated primary tumors were mostly populated by dysfunctional CD4 and CD8 T cells in later stages of differentiation; this, in turn, was correlated with expression changes in the interferon α and γ pathways in epithelial cells, showing that cross-communication between the epithelial and immune compartments is important for immune suppression in HGSC. These findings could have implications for the design of clinical trials with immune-modulating drugs.

DOI: https://doi.org/10.1038/s41698-025-00818-8

Nat Cancer. 2025 Apr 29.

Whole-exome tumor-agnostic ctDNA analysis enhances minimal residual disease detection and reveals relapse mechanisms in localized colon cancer.

In stage 2-3 colon cancer (CC), postsurgery circulating tumor DNA (ctDNA) assessment is crucial for guiding adjuvant chemotherapy (ACT) decisions. While existing assays detect ctDNA and help identify high-risk persons with CC for recurrence, their limited sensitivity after surgery poses challenges in deciding on ACT. Additionally, a substantial portion of persons with CC fail to clear ctDNA after ACT, leading to recurrence. In this study, we performed whole-exome sequencing (WES) of ctDNA at different time points in participants with relapsed CC in two independent cohorts, alongside transcriptomic and proteomic analyses of metastases, to enhance comprehension of progression mechanisms. A plasma WES-based tumor-agnostic assay demonstrated higher sensitivity in detecting minimal residual disease (MRD) compared to current assays. Immune evasion appears to be the primary driver of progression in the localized CC setting, indicating the potential efficacy of immunotherapy for microsatellite stability in persons with CC. Organoid modeling further supports the promising potential of targeted therapy in eradicating MRD, surpassing conventional treatments.

DOI: https://doi.org/10.1038/s43018-025-00960-z

Sci Rep. 2025 Apr 25. 15(1): 14484

Direct cell interactions potentially regulate transcriptional programmes that control the responses of high grade serous ovarian cancer patients to therapy.

Sodiq A Hameed, Walter Kolch, Donal J Brennan, Vadim Zhernovkov.

The tumour microenvironment is composed of a complex cellular network involving cancer, stromal and immune cells in dynamic interactions. A large proportion of this network relies on direct physical interactions between cells, which may impact patient responses to clinical therapy. Doublets in scRNA-seq are usually excluded from analysis. However, they may represent directly interacting cells. To decipher the physical interaction landscape in relation to clinical prognosis, we inferred a physical cell-cell interaction (PCI) network from 'biological' doublets in a scRNA-seq dataset of approximately 18,000 cells, obtained from 7 treatment-naive ovarian cancer patients. Focusing on cancer-stromal PCIs, we uncovered molecular interaction networks and transcriptional landscapes that stratified patients in respect to their clinical responses to standard therapy. Good responders featured PCIs involving immune cells interacting with other cell types including cancer cells. Poor responders lacked immune cell interactions, but showed a high enrichment of cancer-stromal PCIs. To explore the molecular differences between cancer-stromal PCIs between responders and non-responders, we identified correlating gene signatures. We constructed ligand-receptor interaction networks and identified associated downstream pathways. The reconstruction of gene regulatory networks and trajectory analysis revealed distinct transcription factor (TF) clusters and gene modules that separated doublet cells by clinical outcomes. Our results indicate (i) that transcriptional changes resulting from PCIs predict the response of ovarian cancer patients to standard therapy, (ii) that immune reactivity of the host against the tumour enhances the efficacy of therapy, and (iii) that cancer-stromal cell interaction can have a dual effect either supporting or inhibiting therapy responses.

DOI: https://doi.org/10.1038/s41598-025-98463-5