Uncategorized

Blood-based RNA biomarker for the early detection of ovarian cancer

Blood-based RNA biomarker for the early detection of ovarian cancer

  • Webb, P. M. & Jordan, S. J. Global epidemiology of epithelial ovarian cancer. Nat. Rev. Clin. Oncol. 21, 389–400 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Zhang, Y. et al. Global patterns and trends in ovarian cancer incidence: age, period and birth cohort analysis. BMC Cancer 19, 984 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bowtell, D. D. The genesis and evolution of high-grade serous ovarian cancer. Nat. Rev. Cancer 10, 803–808 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 474, 609–615 (2011).

    Article 

    Google Scholar
     

  • Santoro, A. et al. The multiple facets of ovarian high grade serous carcinoma: a review on morphological, immunohistochemical and molecular features. Crit. Rev. Oncol. Hematol. 208, 104603 (2025).

    Article 
    PubMed 

    Google Scholar
     

  • Gaona-Luviano, P., Medina-Gaona, L. A. & Magana-Perez, K. Epidemiology of ovarian cancer. Chin. Clin. Oncol. 9, 47 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Cabasag, C. J. et al. Ovarian cancer today and tomorrow: a global assessment by world region and Human Development Index using GLOBOCAN 2020. Int. J. Cancer 151, 1535–1541 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Penny, S. M. Ovarian cancer: an overview. Radiol. Technol. 91, 561–575 (2020).

    PubMed 

    Google Scholar
     

  • Hong, M. K. & Ding, D. C. Early diagnosis of ovarian cancer: a comprehensive review of the advances, challenges, and future directions. Diagnostics (Basel) 15, 406 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elmadani, M. et al. Cancer burden in Europe: a systematic analysis of the GLOBOCAN database (2022). BMC Cancer 25, 447 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Siegel, R. L., Miller, K. D., Wagle, N. S. & Jemal, A. Cancer statistics, 2023. CA Cancer J. Clin. 73, 17–48 (2023).

    PubMed 

    Google Scholar
     

  • Lheureux, S., Gourley, C., Vergote, I. & Oza, A. M. Epithelial ovarian cancer. Lancet 393, 1240–1253 (2019).

    Article 
    PubMed 

    Google Scholar
     

  • Siegel, R. L., Kratzer, T. B., Giaquinto, A. N., Sung, H. & Jemal, A. Cancer statistics, 2025. CA Cancer J. Clin. 75, 10–45 (2025).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Madan, E. et al. Ovarian tumor cells gain competitive advantage by actively reducing the cellular fitness of microenvironment cells. Nat. Biotechnol. 43, 1833–1847 (2025).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Menon, U. et al. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet 397, 2182–2193 (2021).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buys, S. S. et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA 305, 2295–2303 (2011).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, J. et al. Penetrance of breast and ovarian cancer in women who carry a BRCA1/2 mutation and do not use risk-reducing salpingo-oophorectomy: an updated meta-analysis. JNCI Cancer Spectr. 4, pkaa029 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Slade, E., Berg, L., Dworzynski, K., Manchanda, R. & Guideline, C. Ovarian cancer: identifying and managing familial and genetic risk-summary of new NICE guidance. BMJ 385, q807 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Wei, X. et al. Cost-effectiveness of gene-specific prevention strategies for ovarian and breast cancer. JAMA Netw. Open 7, e2355324 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Manchanda, R. et al. Risk-reducing salpingo-oophorectomy and the use of hormone replacement therapy below the age of natural menopause: scientific impact paper no. 66 October 2021: scientific impact paper no. 66. BJOG 129, e16–e34 (2022).

    CAS 
    PubMed 

    Google Scholar
     

  • Gaba, F. & Manchanda, R. Systematic review of acceptability, cardiovascular, neurological, bone health and HRT outcomes following risk reducing surgery in BRCA carriers. Best Pract. Res. Clin. Obstet. Gynaecol. 65, 46–65 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Sideris, M., Menon, U. & Manchanda, R. Screening and prevention of ovarian cancer. Med. J. Aust. 220, 264–274 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kuhn, E. et al. TP53 mutations in serous tubal intraepithelial carcinoma and concurrent pelvic high-grade serous carcinoma-evidence supporting the clonal relationship of the two lesions. J. Pathol. 226, 421–426 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Shih, I. M., Wang, Y. & Wang, T. L. The origin of ovarian cancer species and precancerous landscape. Am. J. Pathol. 191, 26–39 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Wu, R. C. et al. Genomic landscape and evolutionary trajectories of ovarian cancer precursor lesions. J. Pathol. 248, 41–50 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Labidi-Galy, S. I. et al. High grade serous ovarian carcinomas originate in the fallopian tube. Nat. Commun. 8, 1093 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Krishnan, R. et al. Spatial transcriptomics characterizes high-grade serous ovarian cancer and its precursor lesions. Gynecol. Oncol. 190, S94–S95 (2024).

    Article 

    Google Scholar
     

  • Vang, R. & Shih, I. M. Serous tubal intra-epithelial carcinoma: what do we really know at this point?. Histopathology 81, 542–555 (2022).

    Article 
    PubMed 

    Google Scholar
     

  • Luvero, D. et al. Serous tubal intraepithelial carcinoma (STIC): a review of the literature on the incidence at the time of prophylactic surgery. Diagnostics (Basel) 14, 2577 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Piek, J. M. et al. Dysplastic changes in prophylactically removed fallopian tubes of women predisposed to developing ovarian cancer. J. Pathol. 195, 451–456 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Meserve, E. E. K. et al. Frequency of ‘incidental’ serous tubal intraepithelial carcinoma (STIC) in women without a history of or genetic risk factor for high-grade serous carcinoma: a six-year study. Gynecol. Oncol. 146, 69–73 (2017).

    Article 
    PubMed 

    Google Scholar
     

  • Samimi, G., Trabert, B., Geczik, A. M., Duggan, M. A. & Sherman, M. E. Population frequency of serous tubal intraepithelial carcinoma (STIC) in clinical practice using SEE-Fim protocol. JNCI Cancer Spectr. 2, pky061 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fitzgerald, R. C., Antoniou, A. C., Fruk, L. & Rosenfeld, N. The future of early cancer detection. Nat. Med. 28, 666–677 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Grandi, G. et al. The generally low sensitivity of CA 125 for FIGO stage I ovarian cancer diagnosis increases for endometrioid histotype. Minerva Med. 111, 133–140 (2020).

    Article 
    PubMed 

    Google Scholar
     

  • Zhang, M., Cheng, S., Jin, Y., Zhao, Y. & Wang, Y. Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer. Biochim. Biophys. Acta Rev. Cancer 1875, 188503 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Patrono, M. G. et al. Clinical outcomes in patients with isolated serous tubal intraepithelial carcinoma (STIC): a comprehensive review. Gynecol. Oncol. 139, 568–572 (2015).

    Article 
    PubMed 

    Google Scholar
     

  • Moss, E. L., Hollingworth, J. & Reynolds, T. M. The role of CA125 in clinical practice. J. Clin. Pathol. 58, 308–312 (2005).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li, J. et al. HE4 as a biomarker for ovarian and endometrial cancer management. Expert Rev. Mol. Diagn. 9, 555–566 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Weinberger, V., Bednarikova, M., Cibula, D. & Zikan, M. Serous tubal intraepithelial carcinoma (STIC)—clinical impact and management. Expert Rev. Anticancer Ther. 16, 1311–1321 (2016).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hu, D. et al. Evaluation of serum CA125, HE4 and CA724 and the risk of ovarian malignancy algorithm score in the diagnosis of high-grade serous ovarian cancer. Eur. J. Obstet. Gynecol. Reprod. Biol. 297, 170–175 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Ishizawa, S. et al. Estimating sojourn time and sensitivity of screening for ovarian cancer using a Bayesian framework. J. Natl Cancer Inst. 116, 1798–1806 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Madan, E. et al. Flower isoforms promote competitive growth in cancer. Nature 572, 260–264 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Yekelchyk, M. et al. Flower lose, a cell fitness marker, predicts COVID-19 prognosis. EMBO Mol. Med. 13, e13714 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Rhiner, C. et al. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev. Cell 18, 985–998 (2010).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Costa-Rodrigues, C., Couceiro, J. & Moreno, E. Cell competition from development to neurodegeneration. Dis. Model Mech. 14, dmm048926 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Medina, J. E. et al. Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers. Cancer Discov. 15, 105–118 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Elias, K. M., Guo, J. & Bast, R. C. Jr. Early detection of ovarian cancer. Hematol. Oncol. Clin. North Am. 32, 903–914 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nebgen, D. R., Lu, K. H. & Bast, R. C. Jr. Novel approaches to ovarian cancer screening. Curr. Oncol. Rep. 21, 75 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kamal, R., Hamed, S., Mansour, S., Mounir, Y. & Abdel Sallam, S. Ovarian cancer screening-ultrasound; impact on ovarian cancer mortality. Br. J. Radiol. 91, 20170571 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Havrilesky, L. J., Sanders, G. D., Kulasingam, S. & Myers, E. R. Reducing ovarian cancer mortality through screening: is it possible, and can we afford it?. Gynecol. Oncol. 111, 179–187 (2008).

    Article 
    PubMed 

    Google Scholar
     

  • Myers, E. R. Reducing ovarian cancer mortality through screening: an impossible dream?. J. Natl Cancer Inst. 116, 1712–1714 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Englisz, A., Smycz-Kubanska, M. & Mielczarek-Palacz, A. Sensitivity and specificity of selected biomarkers and their combinations in the diagnosis of ovarian cancer. Diagnostics (Basel) 14, 949 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hada, A. et al. Comparison of the predictive performance of risk of malignancy indexes 1-4, HE4 and risk of malignancy algorithm in the triage of adnexal masses. J. Ovarian Res. 13, 46 (2020).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lof, P. et al. Can serum human epididymis protein 4 (HE4) support the decision to refer a patient with an ovarian mass to an oncology hospital?. Gynecol. Oncol. 166, 284–291 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Welsh, J. B. et al. Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. Proc. Natl Acad. Sci. USA 98, 1176–1181 (2001).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schummer, M. et al. Comparative hybridization of an array of 21,500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene 238, 375–385 (1999).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, F., Shen, J., Wang, J., Cai, P. & Huang, Y. Clinical analysis of four serum tumor markers in 458 patients with ovarian tumors: diagnostic value of the combined use of HE4, CA125, CA19-9, and CEA in ovarian tumors. Cancer Manag. Res. 10, 1313–1318 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nyangoh-Timoh, K., Bendifallah, S., Dion, L., Ouldamer, L. & Leveque, J. Borderline ovarian tumours: CNGOF guidelines for clinical practice—value of tumor markers. Gynecol. Obstet. Fertil. Senol. 48, 277–286 (2020).

    CAS 
    PubMed 

    Google Scholar
     

  • Reilly, G. et al. Analytical validation of a deep neural network algorithm for the detection of ovarian cancer. JCO Clin. Cancer Inform. 6, e2100192 (2022).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Alanbay, I. et al. Comparison of risk of malignancy index (RMI), CA125, CA 19-9, ultrasound score, and menopausal status in borderline ovarian tumor. Gynecol. Endocrinol. 28, 478–482 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Brown, D. L. et al. Benign and malignant ovarian masses: selection of the most discriminating gray-scale and Doppler sonographic features. Radiology 208, 103–110 (1998).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Li, G. et al. Transformer-based AI technology improves early ovarian cancer diagnosis using cfDNA methylation markers. Cell Rep. Med. 5, 101666 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Trinidad, C. V. et al. Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer. Sci. Rep. 13, 18341 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • De Santiago, P. R. et al. LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker. NPJ Precis. Oncol. 9, 62 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bast, R. C. Jr. et al. Biomarkers and strategies for early detection of ovarian cancer. Cancer Epidemiol. Biomarkers Prev. 29, 2504–2512 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Simmons, A. R. et al. Complementary longitudinal serum biomarkers to CA125 for early detection of ovarian cancer. Cancer Prev. Res. (Phila.) 12, 391–400 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, W. L. et al. Human epididymis protein 4 antigen-autoantibody complexes complement cancer antigen 125 for detecting early-stage ovarian cancer. Cancer 126, 725–736 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Guo, J. et al. Osteopontin, macrophage migration inhibitory factor and anti-Interleukin-8 autoantibodies complement CA125 for detection of early stage ovarian cancer. Cancers (Basel) 11, 596 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Muinao, T., Deka Boruah, H. P. & Pal, M. Multi-biomarker panel signature as the key to diagnosis of ovarian cancer. Heliyon 5, e02826 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang, W. L. et al. Elevation of TP53 autoantibody before CA125 in preclinical invasive epithelial ovarian cancer. Clin. Cancer Res. 23, 5912–5922 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Moss, E. et al. British Gynaecological Cancer Society (BGCS) ovarian, tubal and primary peritoneal cancer guidelines: recommendations for practice update 2024. Eur. J. Obstet. Gynecol. Reprod. Biol. 300, 69–123 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Menon, U. et al. Tumour stage, treatment, and survival of women with high-grade serous tubo-ovarian cancer in UKCTOCS: an exploratory analysis of a randomised controlled trial. Lancet Oncol. 24, 1018–1028 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bedia, J. S. et al. Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS. EBioMedicine 112, 105554 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • National Cancer Audit Collaborating Centre. Welcome to the National Ovarian Cancer Audit (NOCA). https://ckan.publishing.service.gov.uk/dataset/national-ovarian-cancer-audit-state-of-the-nation-report-2025 (2025; accessed 18 October 2025).

  • Steenbeek, M. P. et al. Risk of peritoneal carcinomatosis after risk-reducing salpingo-oophorectomy: a systematic review and individual patient data meta-analysis. J. Clin. Oncol. 40, 1879–1891 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kotnik, E. N. et al. Genetic characterization of primary and metastatic high-grade serous ovarian cancer tumors reveals distinct features associated with survival. Commun. Biol. 6, 688 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, J. et al. Cell origins of high-grade serous ovarian cancer. Cancers (Basel) 10, 433 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Barnes, B. M. et al. Distinct transcriptional programs stratify ovarian cancer cell lines into the five major histological subtypes. Genome Med. 13, 140 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bodelon, C. et al. Molecular classification of epithelial ovarian cancer based on methylation profiling: evidence for survival heterogeneity. Clin. Cancer Res. 25, 5937–5946 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dochez, V. et al. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J. Ovarian Res. 12, 28 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang, Q. Y., Feng, X. L., Liu, X. F. & Zhu, S. Y. Prognostic value of elevated pre-treatment serum CA-125 in epithelial ovarian cancer: a meta-analysis. Front. Oncol. 12, 868061 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Funston, G. et al. The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: a population-based cohort study. PLoS Med. 17, e1003295 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Balachandran, A. & Nayak, S. R. An observational study of factors affecting CA125 levels in premenopausal women. Adv. Biomed. Res. 12, 235 (2023).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Duffy, M. J. et al. CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use. Int. J. Gynecol. Cancer 15, 679–691 (2005).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Crawford, S. M. & Evans, C. Outcome of elevated CA125 values from primary care following implementation of ovarian cancer guidelines. Fam. Pract. 35, 199–202 (2018).

    Article 
    PubMed 

    Google Scholar
     

  • Zhang, R., Siu, M. K. Y., Ngan, H. Y. S. & Chan, K. K. L. Molecular biomarkers for the early detection of ovarian cancer. Int. J. Mol. Sci. 23, 12041 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim, S. H. & Weigelt, B. Circulating cell-free (cf)DNA analysis: current technologies and applications in gynecologic cancer. Gynecol. Oncol. Rep. 54, 101431 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mohr, A. E., Ortega-Santos, C. P., Whisner, C. M., Klein-Seetharaman, J. & Jasbi, P. Navigating challenges and opportunities in multi-omics integration for personalized healthcare. Biomedicines 12, 1496 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mattox, A. K. et al. The origin of highly elevated cell-free DNA in healthy individuals and patients with pancreatic, colorectal, lung, or ovarian cancer. Cancer Discov. 13, 2166–2179 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • National Cancer Institute. SEER*Explorer: an interactive website for SEER cancer statistics. Surveillance Research Program. https://seer.cancer.gov/statistics-network/explorer/ (2025; accessed 22 July 2025).

  • National Cancer Institute. SEER Cancer Stat Facts: Ovarian Cancer. https://seer.cancer.gov/statfacts/html/ovary.html (2024; accessed 22 July 2025).

  • Sabelli, R. et al. The challenge of managing isolated STIC lesions: a single-center experience. Gynecol. Oncol. Rep. 58, 101716 (2025).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pepe, M. S., Feng, Z., Janes, H., Bossuyt, P. M. & Potter, J. D. Pivotal evaluation of the accuracy of a biomarker used for classification or prediction: standards for study design. J. Natl Cancer Inst. 100, 1432–1438 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Philpott, S. et al. The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2. J. Med. Genet. 60, 440–449 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Rosenthal, A. N. et al. Evidence of stage shift in women diagnosed with ovarian cancer during phase II of the United Kingdom familial ovarian cancer screening study. J. Clin. Oncol. 35, 1411–1420 (2017).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dagan, E. & Shochat, T. Quality of life in asymptomatic BRCA1/2 mutation carriers. Prev. Med. 48, 193–196 (2009).

    Article 
    PubMed 

    Google Scholar
     

  • Chandrasekaran, D. et al. Implementation of multigene germline and parallel somatic genetic testing in epithelial ovarian cancer: SIGNPOST study. Cancers (Basel) 13, 4344 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Leung, E. Y. et al. British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for genetic testing in epithelial ovarian cancer in the United Kingdom. Int. J. Gynecol. Cancer. 34, 1334–1343 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Manchanda, R. et al. Cost-effectiveness of unselected multigene germline and somatic genetic testing for epithelial ovarian cancer. J. Natl Compr. Canc. Netw. 22, e237331 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Sun, L. et al. A cost-effectiveness analysis of multigene testing for all patients with breast cancer. JAMA Oncol. 5, 1718–1730 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sun, L. et al. Cost-effectiveness of genetic testing for all women diagnosed with breast cancer in China. Cancers (Basel) 14, 1839 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Torr, B. et al. BRCA-DIRECT digital pathway for diagnostic germline genetic testing within a UK breast oncology setting: a randomised, non-inferiority trial. Br. J. Cancer 131, 1506–1515 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Manchanda, R. et al. Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes. BJOG 127, 364–375 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Manchanda, R. & Sideris, M. Population-based genetic testing for cancer susceptibility genes: quo vadis?. BJOG 130, 125–130 (2023).

    Article 
    PubMed 

    Google Scholar
     

  • Manchanda, R. et al. Economic evaluation of population-based BRCA1/BRCA2 mutation testing across multiple countries and health systems. Cancers (Basel) 12, 1929 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sun, L. et al. Economic evaluation of population-based BRCA1 and BRCA2 testing in Canada. JAMA Netw. Open 7, e2432725 (2024).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Torr, B. et al. The NHS England Jewish BRCA Testing Programme: overview after first year of implementation (2023-2024). J. Med. Genet. 62, 69–73 (2025).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Venkatesan, P. BRCA testing launched for people of Jewish ancestry in England. Lancet Oncol. 25, 284 (2024).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Greenberg, R. et al. Carrier screening program for BRCA1/BRCA2 pathogenic variants among Ashkenazi Jewish women in Israel: an observational study. Genet. Med. Open 1, 100824 (2023).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • NHS—Health Research Authority. PROTECT-C: population based germline testing for early detection and prevention of cancer. https://www.hra.nhs.uk/planning-and-improving-research/application-summaries/research-summaries/protect-c_v10/ (2025; accessed 5 August 2025).

  • Gart, J. J. & Nam, J. Approximate interval estimation of the ratio of binomial parameters: a review and corrections for skewness. Biometrics 44, 323–338 (1988).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhang, D., Wang, J., Cai, S. & Surtihadi, J. Skewness-corrected confidence intervals for predictive values in enrichment studies. Stat. Med. 43, 5862–5871 (2024).

    Article 
    PubMed 

    Google Scholar
     

  • Bu, J. et al. An avidity-based PD-L1 antagonist using nanoparticle-antibody conjugates for enhanced immunotherapy. Nano Lett. 20, 4901–4909 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nair, A. et al. Hybrid nanoparticle system integrating tumor-derived exosomes and poly(amidoamine) dendrimers: implications for an effective gene delivery platform. Chem. Mater. 35, 3138–3150 (2023).

    Article 
    CAS 

    Google Scholar
     

  • Mamidi, N. & Delgadillo, R. M. V. Design, fabrication and drug release potential of dual stimuli-responsive composite hydrogel nanoparticle interfaces. Colloids Surf. B Biointerfaces 204, 111819 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Sun, Z., Nyberg, R., Wu, Y., Bernard, B. & Redmond, W. L. Developing an enhanced 7-color multiplex IHC protocol to dissect immune infiltration in human cancers. PLoS ONE 16, e0247238 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Erwied, P. et al. Optimized workflow of EV enrichment from human plasma samples for downstream mass spectrometry analysis. Discov. Oncol. 15, 374 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pinheiro, C. et al. Identification and validation of extracellular vesicle reference genes for the normalization of RT–qPCR data. J. Extracell. Vesicles 13, e12421 (2024).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • R Core Team R: A Language and Environment for Statistical Computing (R Core Team, 2026).

  • Eklund, A. & Trimble, J. beeswarm: The bee swarm plot, an alternative to stripchart. R Package version 0.4.0. CRAN https://CRAN.R-project.org/package=beeswarm (2021).

  • Robin, X. et al. pROC: An open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12, 77 (2011).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • DeLong, E. R., DeLong, D. M. & Clarke-Pearson, D. L. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44, 837–845 (1988).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Youden, W. J. Index for rating diagnostic tests. Cancer 3, 32–35 (1950).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Clopper, C. J. & Pearson, E. S. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika 26, 404–413 (1934).

    Article 

    Google Scholar
     

  • Wilhelm, J. Supporting data and reproducibility code for ‘blood-based RNA biomarker for the early detection of ovarian cancer’ (version 1.0) (data set). Zenodo https://doi.org/10.5281/zenodo.23016074 (2026).

  • Related Posts

    Leave a Reply

    Your email address will not be published. Required fields are marked *