bims-tumhet 2025-07-20 papers

Issue of 2025–07–20
six papers selected by
Sergio Marchini, Humanitas Research

Nature. 2025 Jul 16.

Ongoing genome doubling shapes evolvability and immunity in ovarian cancer.

Andrew McPherson, Ignacio Vázquez-García, Matthew A Myers, Duaa H Al-Rawi, Matthew Zatzman, Adam C Weiner, Samuel Freeman, Neeman Mohibullah, Gryte Satas, Marc J Williams, Nicholas Ceglia, Danguolė Norkūnaitė, Allen W Zhang, Jun Li, Jamie L P Lim, Michelle Wu, Seongmin Choi, Eliyahu Havasov, Diljot Grewal, Hongyu Shi, Minsoo Kim, Roland F Schwarz, Tom Kaufmann, Khanh Ngoc Dinh, Florian Uhlitz, Julie Tran, Yushi Wu, Ruchi Patel, Satish Ramakrishnan, DooA Kim, Justin Clarke, Hunter Green, Emily Ali, Melody DiBona, Nancy Varice, Ritika Kundra, Vance Broach, Ginger J Gardner, Kara Long Roche, Yukio Sonoda, Oliver Zivanovic, Sarah H Kim, Rachel N Grisham, Ying L Liu, Agnes Viale, Nicole Rusk, Yulia Lakhman, Lora H Ellenson, Simon Tavaré, Samuel Aparicio, Dennis S Chi, Carol Aghajanian, Nadeem R Abu-Rustum, Claire F Friedman, Dmitriy Zamarin, Britta Weigelt, Samuel F Bakhoum, Sohrab P Shah.

Whole-genome doubling (WGD) is a common feature of human cancers and is linked to tumour progression, drug resistance, and metastasis1-6. Here we examine the impact of WGD on somatic evolution and immune evasion at single-cell resolution in patient tumours. Using single-cell whole-genome sequencing, we analysed 70 high-grade serous ovarian cancer samples from 41 patients (30,260 tumour genomes) and observed near-ubiquitous evidence that WGD is an ongoing mutational process. WGD was associated with increased cell-cell diversity and higher rates of chromosomal missegregation and consequent micronucleation. We developed a mutation-based WGD timing method called doubleTime to delineate specific modes by which WGD can drive tumour evolution, including early fixation followed by considerable diversification, multiple parallel WGD events on a pre-existing background of copy-number diversity, and evolutionarily late WGD in small clones and individual cells. Furthermore, using matched single-cell RNA sequencing and high-resolution immunofluorescence microscopy, we found that inflammatory signalling and cGAS-STING pathway activation result from ongoing chromosomal instability, but this is restricted to predominantly diploid tumours (WGD-low). By contrast, predominantly WGD tumours (WGD-high), despite increased missegregation, exhibited cell-cycle dysregulation, STING1 repression, and immunosuppressive phenotypic states. Together, these findings establish WGD as an ongoing mutational process that promotes evolvability and dysregulated immunity in high-grade serous ovarian cancer.

DOI: https://doi.org/10.1038/s41586-025-09240-3

Front Oncol. 2025 ;15 1594100

Clinical utility of various liquid biopsy samples for the early detection of ovarian cancer: a comprehensive review.

Yueqi Feng, Wanjun Yang, Jingyu Zhu, Shirui Wang, Ningjuan Wu, Hanzhi Zhao, Xiaofeng Yang.

Ovarian cancer (OC) is a highly lethal gynecologic malignancy because of the absence of specific early symptoms and reliable biomarkers, most OC patients are often diagnosed at advanced stages, resulting in poor prognosis. Traditional tissue biopsy and serological biomarkers like CA125 have limited clinical application. Therefore, there is an urgent demand for effective diagnostic and screening tools in clinical practice. Liquid biopsy is a non-invasive method for early cancer detection by analyzing tumor-associated components shed into different body fluids, for example, circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), cell-free RNA, proteins, and metabolites. Increasing evidence has demonstrated that liquid biopsy is promising for detecting cancer at an early stage. In this review, we outline the results for the utility of each liquid biopsy fluid, including serum/plasma, urine, cervical/vaginal sample, uterine lavage, and summarize the advantages and current constraints associated with their application in clinical settings. Future directions and challenges are also highlighted, along with areas where more research is warranted.

Keywords: biomarkers; early detection; liquid biopsy; multi-omics; ovarian cancer

DOI: https://doi.org/10.3389/fonc.2025.1594100

Clin Cancer Res. 2025 Jul 15.

Transcriptome Analysis of Matched Cohorts of Long- and Short-term Survivors in Advanced High-Grade Serous Tubo-ovarian Cancer.

Sofya Marchenko, Niklas Goernitz, Wiebke Alina Zoern, Maria Joosten, Inga Hoffmann, Jalid Sehouli, Gerald Niedobitek, Carsten Denkert, Bruno V Sinn, Svenja Kolb, José Carbonell-Caballero, Alfonso Valencia, Mihnea P Dragomir, Wolfgang D Schmitt, David Horst, Ioana I Braicu, Christine Sers, Jonathan Pohl, Eliane T Taube.

OBJECTIVE: The late-stage diagnosis and the aggressiveness of high-grade serous tubo-ovarian carcinoma (HGSC) often results in poor survival outcomes, yet some patients exhibit an exceptionally long survival rate.This study aimed to identify molecular profiles associated with long-term/short-term survival in HGSC, with the goal of better understanding protective factors and developing new treatments.
EXPERIMENTAL DESIGN: To discover molecular drivers causing aggressiveness of HGSC, tumor samples from 12 long-term HGSC survivors (> 7 years overall survival) and 12 short-term survivors (< 1 year overall survival) were analyzed using targeted RNA sequencing followed by computational analysis. We investigated differentially expressed genes and their functional relevance, inferred differences in cell-type composition and signaling pathways as well as mutation status. To validate our findings, we simulated our study design by using HGSC TCGA dataset samples. We evaluated differential patterns of gene expression between these two groups and developed molecular profiles of HGSC that correlate with survival phenotypes.
RESULTS: Besides known molecular cancer drivers and indicators of poor prognosis, we identified specific transcriptional changes between short-term and long-term survivors of HGSC which indicate that immune processes play a fundamental role in long-term survivors. Our computational analysis reveals an important role of the ensemble of IFN-γ signaling and the RFX transcription factors as well as the immune cell composition of the tumor microenvironment.
CONCLUSION: Specific immunologic requirements involving IFN-γ signaling and affected pathways seem to be relevant for long term survival in the generally considered non-immunogenic HGSC, requesting further research to improve diagnostic strategies and targeted therapies.

DOI: https://doi.org/10.1158/1078-0432.CCR-24-2794

Crit Rev Anal Chem. 2025 Jul 16. 1-16

Liquid Biopsy-Based Smart Sensors for Ovarian Cancer Detection.

Pallavi Kumari, Anupama Aiyar, Shweta Dang.

Ovarian cancer is one of the most aggressive gynecologic malignancies, with a vast majority of patients diagnosed at advanced stages owing to the lack of available early detection methods. Liquid biopsy, a noninvasive method for detecting circulating biomarkers such as circulating tumor cells (CTCs), cell-free DNA (cfDNA), exosomes, and a wide range of non-coding RNAs (including microRNAs, long non-coding RNAs, and circular RNAs), enables the detection of ovarian cancer using composite biomarker panels tailored for disease specificity. Liquid biopsy-based diagnostics have also made a significant leap forward in terms of sensitivity, specificity, and real-time monitoring due to integration of smart sensor technology. To meet the challenge of sensitivity, highly specific bioelectrical and electrochemical, optical as well and nanomaterial-based sensors have been developed to detect ovarian cancer biomarkers within minutes that are cost-effective and scalable. The progress of Lab-on-Chip technologies, nano-bio sensing systems, and artificial intelligence-driven diagnostic models have further redefined this field by increasing biomarker detection and facilitating clinical decision-making efficiencies. This review discusses the state-of-the-art of liquid biopsy in smart sensors, their fundamentals, and the breakthroughs of these technologies of interest for ovarian cancer detection. Moreover, both clinical utility and regulatory hurdles of this biosensing will be interpreted to decipher the translational readiness for broad clinical application. The smart biosensors will continue to evolve, determining the future of ovarian cancer diagnostics by providing early detection and personalized treatment options and quality of life for patients.

Keywords: cDNA; electrochemical sensor; liquid biopsy; miRNA; ovarian cancer

DOI: https://doi.org/10.1080/10408347.2025.2530177