bims-tumhet 2026-03-15 papers

Issue of 2026–03–15
three papers selected by
Sergio Marchini, Humanitas Research

Clin Epigenetics. 2026 Mar 08.

Circulating tumor DNA methylation-based method for noninvasive detection and stage stratification of colorectal tumor.

Hongli Ji, Mimi Xu, Wei Jiang, Yaowen Hu, Botao Yan, Qiaolin Chen, Jixiang Zheng, Wei Wu, Xiarong Hu, Zhenbang Chen, Zelong Han, Hanlin Lu, Jun Yan.

BACKGROUND: Early detection and optimal treatment could improve the outcomes of patients with colorectal cancer (CRC). No adequate method has been developed to meet these two requirements. Here, we aimed to identify differential circulating tumor DNA (ctDNA) methylation biomarkers associated with CRC, and then establish models for detection, stage stratification and clinical decision-making.
RESULTS: A total of 636 participants were included in this prospective study. To identify differential ctDNA methylation biomarkers, we first performed a genome-wide analysis between tumor and adjacent normal tissues using the α-value, which is sensitivity to ctDNA methylation signals. After filtering with PBMC samples, 4965 biomarkers were identified. A panel of 21 biomarkers was selected after shrinkage. A ctDNA methylation-based CRC diagnostic model (cMCD) was constructed. The cMCD yielded a sensitivity of 87.82% (83.39%-91.41%) for the combined detection of advanced adenomas and CRC, and a specificity of 91.88% (88.54%-94.49%). The overall accuracy was 89.85% (87.50%-92.30%), which was much greater than that of tumor markers [CEA: 67.30% (63.50%-70.93%); CA19-9: 59.91% (55.98%-63.74%); CA72-4: 55.66% (51.70%-59.57%); all P < 0.001]. As the risk score and sensitivity of the cMCD tended to increase with tumor progression, we constructed another ctDNA methylation-based model to stratify stage (cMCSS) and further guide treatment selection, specifically for discriminating the Early-stage patients eligible for curative endoscopic resection and avoiding overtreatment. The cMCSS could discriminate 75.86% (68.81%-82.02%) of Early-stage patients (advanced adenomas and T1N0M0 CRCs), for whom endoscopic resection could achieve curative intent, and 89.45% (84.59%-93.19%) of Advanced-stage patients. The accuracy [83.42% (79.36%-86.96%)] was significantly greater than that of tumor markers [CEA: 60.20% (55.17%-65.08%); CA19-9: 51.77% (46.71%-56.83%); CA724: 46.17% (41.16%-51.25%); all P < 0.001].
CONCLUSIONS: The approach based on ctDNA methylation is a noninvasive and robust method for both early detection and tumor stratification of CRC and could benefit patients in clinical decision-making.

Keywords: Biomarker; Colorectal cancer; Early detection; Stage stratification; ctDNA methylation

DOI: https://doi.org/10.1186/s13148-026-02097-x

Gynecol Oncol. 2026 Mar 11. pii: S0090-8258(26)00812-7. [Epub ahead of print]208 1-7

Peritoneal cancer risk after risk reducing salpingo-oophorectomy, impact of mutational status and STIC lesions.

Claire Saule, Enora Laas, Nina Weber, Guillaume Bataillon, Veronique Becette, Julie Perlbarg-Samson, Nicolas Pouget, Anne Donnadieu, Aullène Toussaint, Chrystelle Colas, Anne Vincent-Salomon, Sophie Frank, Eric Pasmant, Dominique Stoppa-Lyonnet, Virginie Fourchotte, Emmanuelle Mouret-Fourme.

BACKGROUND: Women with inherited susceptibility or a strong family history of ovarian cancer, particularly carriers of pathogenic BRCA1/2 variants, face a markedly increased lifetime risk. To mitigate this risk, current guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) between ages 35 and 40 for BRCA1 and between ages 40 and 45 for BRCA2 METHODS: We conducted an ambispective multicenter study in France including 1351 women at high risk of ovarian cancer, 984 of whom carried BRCA1/2 pathogenic variants, totaling 7433.3 woman-years of follow-up. When histological reports from RRSO revealed abnormalities, surgical specimens were reviewed, with special focus on the fallopian tubes to identify serous tubal intraepithelial carcinoma (STIC). The incidence of peritoneal carcinoma (PC) after RRSO was recorded.
RESULTS: STIC was detected in 14 patients at RRSO (10 BRCA1; 2 BRCA2 carriers). During follow-up, 4 women developed PC, corresponding to a 5-years cumulative incidence of 0.4% in the overall cohort and 0.5% among BRCA1/2 carriers. Age at surgery was significantly associated with pathological findings: invasive carcinoma was detected at a median age of 55 years, STIC at 54 years, and benign lesions at 51 years (p < 0.001). Notably, women with STIC at RRSO had a 5-year PC risk of 11.1%.
CONCLUSIONS: These findings highlight the importance of early RRSO, meticulous tubal evaluation, and extended post-surgical surveillance in genetically at-risk women. Detection of STIC warrants tailored follow-up strategies. Further studies are needed to assess the effectiveness and morbidity of staging surgery or regular monitoring using CA125 or innovative markers such as ctDNA.

Keywords: BRCA1 and BRCA2 genes; Breast and ovarian predisposition; Ovarian cancer risk; Peritoneal cancer risk; RRSO; STIC

DOI: https://doi.org/10.1016/j.ygyno.2026.02.019

NPJ Precis Oncol. 2026 Mar 10.

Copy number alteration fingerprint predicts the clinical response of oxaliplatin-based chemotherapy in metastatic colorectal cancer.

Junyong Weng, Jinyu Wang, Ziyu Tao, Tao Wu, Kaixuan Diao, Jiexuan Wang, Nan Wang, Zilan Ye, Ruoxin Zhang, Jiayu Shen, Xiangyu Zhao, XinXing Li, Xinxiang Li, Xue-Song Liu.

Oxaliplatin-based chemotherapy is a standard treatment for metastatic colorectal cancer (mCRC), yet accurate biomarkers to identify responders remain lacking. In this study, we developed and validated a genomic copy number alteration (CNA)-based biomarker to predict clinical response to oxaliplatin-based chemotherapy. A total of 297 samples were collected, and shallow sequencing was employed to extract CNA features. The resulting model named "CNA fingerprint" is an XGBoost model trained using 7 CNA features. The model was validated across three independent test cohorts from two centers, achieving area under the receiver operating characteristic curve (AUC) of 0.87, 0.87, and 0.85, respectively. The primary predictor was the number of DNA segments with high absolute copy numbers. Our findings suggest that the CNA fingerprint could be used as biomarker for oxaliplatin-based chemotherapy response prediction in mCRC. Further prospective clinical trials are warranted to evaluate CNA fingerprint's performance in clinical applications.

DOI: https://doi.org/10.1038/s41698-026-01354-9