bims-ovdlit Biomed News
on Ovarian cancer: early diagnosis, liquid biopsy and therapy
Issue of 2026–06–21
sixteen papers selected by
Lara Paracchini, Humanitas Research
  1. Occult invasive and preneoplastic lesions at risk-reducing salpingo-oophorectomy in BRCA1/2 carriers: A multicenter retrospective cohort study.
  2. When Is a Test "Genetic?" The Case of Multi-Cancer Early Detection Tests.
  3. Reply to: "On the Distinction Between Prognostic and Predictive Inference in Multicancer Early Detection" and "Interpretation of Survival Outcomes in Multicancer Early Detection Testing Requires Caution".
  4. Can ovarian cancer screening work? A secondary analysis of the UK collaborative trial of ovarian cancer screening.
  5. 3D multi-omics tumour atlases: from technology to biology and clinical translation.
  6. Longitudinal genome-wide aneuploidy measurements in circulating cell-free DNA to predict lack of benefit from pembrolizumab in patients with metastatic urothelial cancer.
  7. Repurposing the liquid-based Pap test for the detection of ovarian cancer protein biomarkers.
  8. New standards and new constraints redefine treatment sequencing in platinum-resistant ovarian cancer.
  9. Liquid biopsy in gynecologic cancers: Cellular origin to early detection and precision care.
  10. The TRUST trial in ovarian cancer: a missed opportunity or a turning point? The position of the Italian MITO group.
  11. On the Distinction Between Prognostic and Predictive Inference in Multicancer Early Detection.
  12. Tumor-derived cell-free DNA detected in cerebrospinal fluid enables minimally invasive profiling of pediatric brain tumors.
  13. Genetic origins and constraints of evolutionary innovation.
  14. No prognostic role for FIGO grading in mismatch repair deficient endometrial carcinoma.
  15. Decoding common and rare noncoding variant effects across cellular and developmental contexts.
  16. Liquid biopsy-based diagnostic evaluation of hypermethylated CpG sites for ovarian cancer diagnosis.
  1. Gynecol Oncol. 2026 Jun 19. pii: S0090-8258(26)02033-0. [Epub ahead of print]211 29-36
    Occult invasive and preneoplastic lesions at risk-reducing salpingo-oophorectomy in BRCA1/2 carriers: A multicenter retrospective cohort study.
    Mauro Francesco Pio Maiorano, Gennaro Cormio, Irma De Serio, Francesca Pia Torzillo, Maria Antonietta Ramunno, Brunella Pilato, Michele Mongelli, Claudia Carella, Emanuele Naglieri, Brigida Anna Maiorano, Erica Silvestris, Vera Loizzi.
       OBJECTIVE: To evaluate the prevalence and spectrum of occult invasive or preneoplastic lesions detected at risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 carriers and to describe recurrent BRCA variants in a regional multicenter cohort.
    METHODS: This multicenter retrospective cohort study included 291 women with documented germline pathogenic BRCA1/2 alterations who underwent RRSO at three referral centers in Apulia, Italy, between 2020 and 2025. The primary endpoint was occult invasive or microinvasive tubo-ovarian malignancy at final histopathology. Secondary endpoints included serous tubal intraepithelial carcinoma (STIC), the distribution of histopathologic findings, distribution according to BRCA group, and recurrent annotated BRCA variants.
    RESULTS: After excluding one patient with ovarian metastasis, occult invasive or microinvasive tubo-ovarian malignancy was identified in 24/290 patients (8.3%), while STICs were identified in 5/290 (1.7%). STIL was observed in 3/291 patients (1.0%). Overall, 29/290 patients (10.0%; 95% confidence interval 7.1-14.0) met the composite endpoint of occult invasive or microinvasive primary tubo-ovarian malignancy or STIC. Among pathogenic variant carriers, the prevalence of the same endpoint was 20/159 (12.6%) in BRCA1 carriers and 9/131 (6.9%) in BRCA2 carriers (p = 0.119). Specific BRCA mutation was available for 154/291 patients (52.9%); BRCA1 c.5266dupC was the most frequent recurrent annotated variant, accounting for 43/154 (27.9%) annotated variants overall and 43/81 (53.1%) annotated BRCA1 variants.
    CONCLUSIONS: In this multicenter BRCA1/2 cohort, occult invasive or microinvasive primary tubo-ovarian malignancy and STIC were identified in approximately one in ten women undergoing RRSO. Most positive cases represented occult invasive or microinvasive malignancy, and BRCA1 c.5266dupC emerged as the dominant recurrent regional variant.
    Keywords:  BRCA1; BRCA2; RRSO surgery; STIC lesion ovarian cancer; ovarian cancer; risk-reducing salpingo-oophorectomy BRCA; serous tubal intraepithelial carcinoma
    DOI:  https://doi.org/10.1016/j.ygyno.2026.06.013
  2. J Insur Med. 2026 Jun 15. 53(2): 217-220
    When Is a Test "Genetic?" The Case of Multi-Cancer Early Detection Tests.
    Timothy Meagher.
      Multi-cancer early detection (MCED) tests are increasingly popular. Are these tests "genetic," and if so, can insurers use them in the risk assessment process? This article reviews definitions of genetic tests. It then reviews the motivation for limiting insurers' access to genetic tests and examines the wording in the legislation in 3 English speaking jurisdictions. It then attempts to establish whether MECD results are included in the legislation.
    Keywords:  Epigenetic test; Fragmentomics; Genetic Test; Germline testing; Hereditary genetic disorder; Metabolomics; Methylation patterns; Multi-cancer early detection test; Proteomics; Somatic testing
    DOI:  https://doi.org/10.17849/insm-53-2-1-4.1B
  3. JCO Precis Oncol. 2026 Jun;10(6): e2600523
    Reply to: "On the Distinction Between Prognostic and Predictive Inference in Multicancer Early Detection" and "Interpretation of Survival Outcomes in Multicancer Early Detection Testing Requires Caution".
    Charles Swanton.
      
    DOI:  https://doi.org/10.1200/PO-26-00523
  4. Br J Cancer. 2026 Jun 13.
    Can ovarian cancer screening work? A secondary analysis of the UK collaborative trial of ovarian cancer screening.
    Jane M Lange, Ishfaq Ahmad, Isabel J Dengos, Andy Ryan, Sophia Apostolidou, Aleksandra Gentry-Maharaj, Shannon Holloway, Marc D Ryser, Usha Menon, Ruth Etzioni.
       BACKGROUND: The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS; 2001-2020) showed no reduction in disease mortality in its primary intervention arm using multimodal screening (MMS) with longitudinal Cancer Antigen 125 (CA125) and transvaginal ultrasound. Whether this null result reflects the stop-screen design, screening performance, or ovarian cancer natural history remains unclear.
    METHODS: Using individual-level screening and diagnosis data from the MMS arm, we estimated ovarian cancer natural history, focusing on high-grade serous ovarian cancer (HGSC), the most common and lethal subtype. We then simulated trial outcomes under (1) continued screening beyond the trial screening interval and (2) high sensitivity for early-stage detection over an extended time period.
    RESULTS: The estimated window for detecting early-stage HGSC under MMS was <6 months. Continued screening yielded at most a 15% relative mortality reduction. Achieving a ≥20% mortality reduction required extending the detectable early-stage window to 1 year and attaining ≥70% sensitivity during this period.
    CONCLUSION: Current screening modalities offer a very limited opportunity to intercept HGSC at an early stage. Clinically effective ovarian cancer screening will require first- and second-line tests capable of detecting HGSC substantially earlier in its natural history.
    DOI:  https://doi.org/10.1038/s41416-026-03490-2
  5. Nat Rev Cancer. 2026 Jun 15.
    3D multi-omics tumour atlases: from technology to biology and clinical translation.
    Miao Liu, Jorge Villazon, André Forjaz, Xiaolong Tian, Rong Fan, Siyuan Wang, Lingyan Shi, Denis Wirtz, Ashley L Kiemen.
      Human tumours consist of highly heterogeneous and interacting cell types organized within a complex 3D space, forming a dynamic ecosystem that evolves through the development of pre-malignant lesions, tumour initiation, progression, invasion and metastasis. Understanding the operational principles of tumour evolution at a holistic 3D level is critical for improving the ability to intercept and treat cancer early. Emerging technologies in spatial multi-omics and the generation of 3D tumour atlases are beginning to address this critical need. These efforts aim to capture the intricate interactions within precancerous lesions, tumours and their surrounding ecosystems over space and time. In this Review, we highlight emerging tools developed within and beyond the tumour atlas community and explore their potential in constructing comprehensive 3D tumour atlases. Such atlases have the potential to reveal novel biomarkers for risk stratification, early detection, preventive intervention, and transformative diagnostic and treatment strategies. Furthermore, a 3D tumour atlas can generate new insights into the molecular and cellular mechanisms driving human tumour evolution, paving the way for future research and innovation in cancer biology.
    DOI:  https://doi.org/10.1038/s41568-026-00940-0
  6. Mol Oncol. 2026 Jun 16.
    Longitudinal genome-wide aneuploidy measurements in circulating cell-free DNA to predict lack of benefit from pembrolizumab in patients with metastatic urothelial cancer.
    Youssra Salhi, Stavros Makrodimitris, Sandra van Wilpe, Iris Te Paske, Vanja de Weerd, Corine M Beaufort, Hans M Westgeest, Jens Voortman, Maureen J B Aarts, Maud Rijnders, Astrid A M van der Veldt, Ronald de Wit, Niven Mehra, Saskia M Wilting, Debbie G J Robbrecht.
      Accurate prediction of lack of benefit from pembrolizumab in patients with metastatic urothelial cancer (mUC) is an unmet need. We investigated the dynamics of circulating tumor DNA (ctDNA) load, estimated using the modified fast aneuploidy screening test-sequencing system (mFast-SeqS), as a potential biomarker for early on-treatment identification of treatment response. A total of 104 patients with mUC treated with pembrolizumab from two prospective biomarker discovery trials were included and mFast-SeqS was performed on paired blood samples collected at baseline and on-treatment. Patients with a high on-treatment aneuploidy score (≥ 5, n = 26) had a shorter median OS than patients with a low (< 5) score (n = 76) (3 vs 17 months: P-value< 0.001). Patients with an increased (n = 10), stable (n = 66), or decreased (n = 28) on-treatment score relative to their baseline score had a median PFS of 1.5, 4.0, and 8.3 months, respectively. Median OS was 3.0, 11.1, and 18.7 months, respectively. In patients with mUC treated with pembrolizumab, the on-treatment mFast-SeqS-based ctDNA level and its dynamics relative to baseline are independent prognostic markers that can be used to identify patients that are unlikely to benefit from pembrolizumab.
    Keywords:  circulating tumor DNA; metastatic urothelial cancer; modified fast aneuploidy screening test‐sequencing system; pembrolizumab
    DOI:  https://doi.org/10.1002/1878-0261.70272
  7. Clin Proteomics. 2026 Jun 17.
    Repurposing the liquid-based Pap test for the detection of ovarian cancer protein biomarkers.
    Amy P N Skubitz, Kristin L M Boylan, Limeng Liu, Ashley Petersen, Yuqian Gao, Joshua R Hansen, Jesse B Trejo, Thomas L Fillmore, Yang Wang, Melissa A Geller, Peter A Argenta, Samantha Hoffman, Karin Rodland, Tao Liu, Paul D Piehowski.
       BACKGROUND: Earlier detection is strongly associated with increased survival for women with ovarian cancer. Unfortunately, current screening strategies, employing serial serum or ultrasound assessments, lack adequate sensitivity and specificity for use in the low-prevalence general population. In contrast, screening for cervical cancer by Pap tests has been routinely performed for over 50 years. Since ovarian cancer cells have been observed in Pap tests, ovarian cancer protein biomarkers may also be present; yet Pap samples have not been rigorously examined for diagnostic proteins. Assessment of cervical effluent, as can be collected in a Pap test, has the potential to differentiate ovarian cancer cases from healthy controls, and thereby demonstrate that intra-abdominal pathology may be detected using this commonly acquired specimen. We hypothesize that proteins shed by ovarian cancer cells can be detected in the SurePath™ liquid-based Pap test fixative using mass spectrometry (MS)-based proteomics, making it possible to distinguish women with ovarian cancer from healthy women.
    METHODS: Candidate ovarian cancer biomarkers were successfully identified in liquid-based Pap test samples from 20 cases of high grade serous ovarian cancer, 10 benign ovarian conditions, and 10 healthy control samples, by performing Tandem Mass Tag™ isobaric labeling, 2D liquid chromatography-MS/MS, and bioinformatics integration. Selected reaction monitoring (SRM) MS-based targeted proteomics was then performed using a panel of candidate biomarkers to quantify their abundance in an expanded patient cohort of 90 liquid-based Pap tests.
    RESULTS: A multi-protein classifier was developed using the SRM-MS data comprised of 6 proteins and achieving an AUC of 0.880 (95% CI: 0.738-0.989); sensitivity at 90% specificity was 0.800.
    CONCLUSION: This pilot study provides evidence that the cervical effluent collected in SurePath™ fixative from Pap tests has the potential to be used as a biospecimen for the detection of ovarian cancer proteins. Our long-term goal is to develop a noninvasive screening test that can be incorporated into a routine Pap test or a self-administered home test, so that women can be screened simultaneously for cervical and ovarian cancer.
    Keywords:  Biomarker; Mass spectrometry-based proteomics; Ovarian cancer detection; Pap test
    DOI:  https://doi.org/10.1186/s12014-026-09610-7
  8. Nat Rev Clin Oncol. 2026 Jun 17.
    New standards and new constraints redefine treatment sequencing in platinum-resistant ovarian cancer.
    Isabelle Ray-Coquard, Kathleen N Moore.
      
    DOI:  https://doi.org/10.1038/s41571-026-01168-5
  9. Pathol Res Pract. 2026 Jun 16. pii: S0344-0338(26)00244-X. [Epub ahead of print]286 156591
    Liquid biopsy in gynecologic cancers: Cellular origin to early detection and precision care.
    Mokhtar Rejili, Najma Farahani, Farid Hashemi.
      Gynecological cancers, encompassing malignancies of the cervix, vagina, uterus, fallopian tubes, and ovaries, remain a significant global health burden despite advances in cancer therapeutics and epidemiological trends. According to the International Agency for Research on Cancer (IARC), these neoplasms account for approximately 19% of nearly 5 million new cancer cases and 3 million deaths annually, disproportionately impacting women in low- and middle-income countries. Traditional diagnostic approaches, including histological tumor biopsies, play a critical role in cancer classification and molecular characterization; however, such invasive procedures pose limitations related to patient suitability, procedural risks, and sampling biases due to tumor heterogeneity. This scenario highlights the urgent need for innovative, minimally invasive diagnostic modalities capable of early detection and personalized disease management. Liquid biopsy has emerged as a promising noninvasive alternative, harnessing circulating tumor-derived biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), tumor-educated platelets (TEPs), extracellular vesicles (EVs), and circulating RNAs. Since the first identification of ctDNA in female-specific malignancies in 2012, there have been substantial technological advances over the past decade that underscore the clinical potential of liquid biopsies in gynecological oncology. These circulating biomarkers provide dynamic insights into tumor genetics and heterogeneity, facilitating early diagnosis, prognostication, and real-time monitoring while circumventing the limitations of tissue biopsies. This review highlights current evidence on liquid biopsy applications for gynecological cancers, focusing on recent methodological progress, biomarker validation, and diagnostic utility. Furthermore, it addresses existing challenges related to sensitivity, specificity, and standardization, emphasizing the translational prospects of liquid biopsy in enhancing personalized management and improving clinical outcomes for women afflicted with gynecological malignancies.
    Keywords:  Biomarkers; Circulating Tumor DNA; Gynecologic Neoplasms; Liquid Biopsy; Molecular Diagnostic Techniques; Precision Medicine
    DOI:  https://doi.org/10.1016/j.prp.2026.156591
  10. Front Oncol. 2026 ;16 1853078
    The TRUST trial in ovarian cancer: a missed opportunity or a turning point? The position of the Italian MITO group.
    Martina Arcieri, Sandro Pignata, Domenica Lorusso, Anna Fagotti, Vito Chiantera, Antonino Ditto, Giorgio Valabrega, Claudia Marchetti, Claudio Zamagni, Valentina Tuninetti, Alberto Farolfi, Stefano Restaino, Giuseppe Vizzielli.
      
    Keywords:  Cytoreduction; neoadjuvant chemotherapy; ovarian cancer; randomized clinical trial; surgery
    DOI:  https://doi.org/10.3389/fonc.2026.1853078
  11. JCO Precis Oncol. 2026 Jun;10(6): e2600388
    On the Distinction Between Prognostic and Predictive Inference in Multicancer Early Detection.
    Luis Bermúdez-Guzmán.
      
    DOI:  https://doi.org/10.1200/PO-26-00388
  12. J Clin Invest. 2026 06 15. pii: e197391. [Epub ahead of print]136(12):
    Tumor-derived cell-free DNA detected in cerebrospinal fluid enables minimally invasive profiling of pediatric brain tumors.
    Liana Nobre, Yoshiko Nakano, Ian Burns, Robert Siddaway, Michal Zápotocky, Monique Johnson, Mansuba Rana, Cyril Li, Rodney K Lyn, Richard Yuditskiy, Michelle Ku, Javal Sheth, Adrian B Levine, Cody L Nesvick, Anirban Das, Chantel Cacciotti, Shayna Zelcer, Seth A Climans, Maria MacDonald, Logine Negm, Jiil Chung, Julie Bennett, Andrew Bondoc, Jim Loukides, Lucie Stengs, Melissa Edwards, Eric Bouffet, Vijay Ramaswamy, Anthony Py Liu, Annie Huang, Ute Bartels, Peter B Dirks, Uri Tabori, Cynthia Hawkins.
      BACKGROUNDLiquid biopsy has emerged as a minimally invasive method for tumor diagnosis, monitoring, and therapeutic guidance. For CNS tumors, cerebrospinal fluid (CSF) provides a reliable and accessible source of tumor-derived cell-free DNA (ctDNA).METHODSThis study evaluates the clinical utility of CSF liquid biopsy in a real-world prospective setting. A total of 148 CSF samples from 120 patients underwent molecular analysis using droplet digital PCR (ddPCR) and/or next-generation sequencing to detect mutations, fusions, copy number alterations, and mismatch-repair deficient signatures (MMRDness). Samples were collected via lumbar puncture (n = 82; 45% ctDNA positive) or from ventricle sources at the time of surgery or through shunts (n = 66; 65% ct DNA positive).RESULTSOverall, ctDNA was detected in 54% of samples with higher detection in high-grade gliomas at diagnosis (100%, 1 sample equivocal) compared with low-grade gliomas (50%). Among low-grade gliomas, ctDNA detection was higher in disseminated cases (80% versus 43%) and from ventricular versus lumbar samples (56% versus 38%).CONCLUSIONLiquid biopsy distinguished relapse from second malignancy and serial sampling demonstrated the potential for ctDNA levels to track treatment response and disease progression. In patients with MMRD tumors, high MMRDness score from ctDNA supported active disease. These findings demonstrate that combined liquid biopsy assays facilitate diagnosis, monitoring, and personalized treatment decisions, offering a viable alternative to invasive surgical biopsies in pediatric CNS tumors.TRIAL REGISTRATIONNone.FUNDINGProof of Principle Grant from The Hospital for Sick Children; The Canadian Institutes of Health Research; The Canadian Cancer Society; The We Love You Connie Foundation; Garron Family Cancer Center at SickKids; SickKids Clinician Training Program; Ben Stelter Foundation through the Women and Children's Health Research Institute; Jeffrey Brock Cancer Genetics Research Fellowship; Garron Family Cancer Center Research Fellowship/Scotiabank Clinician Scientist Fellowship; Atrium/CMCC and Hold'em for Life Oncology Fellowship; Tokyo Children's Cancer Study Group Scholarship of the Gold Ribbons Network.
    Keywords:  Brain cancer; Drug therapy; Genetics; Molecular diagnosis; Neuroscience; Oncology
    DOI:  https://doi.org/10.1172/JCI197391
  13. Nat Rev Genet. 2026 Jul;27(7): 499-500
    Genetic origins and constraints of evolutionary innovation.
      
    DOI:  https://doi.org/10.1038/s41576-026-00983-x
  14. Eur J Cancer. 2026 Jun 13. pii: S0959-8049(26)00666-0. [Epub ahead of print]244 116885
    No prognostic role for FIGO grading in mismatch repair deficient endometrial carcinoma.
    Famke C Wakkerman, Cathalijne C B Post, Gitte Ørtoft, Estrid Høgdall, Jan J Jobsen, Rubina Razack, Cor D de Kroon, Remi A Nout, Dorine S J Tseng, Nienke Kuijsters, Marie A D Haverkort, Melanie E Powell, Alexandra Leary, Linda R Mileshkin, Pearly Khaw, Lois E Shepherd, Stephanie M de Boer, Judith R Kroep, Vincent T H B M Smit, Carien L Creutzberg, Nanda Horeweg, Tjalling Bosse.
       INTRODUCTION: The prognostic value of FIGO grading in endometrial cancer (EC) varies across molecular subgroups: it is no longer considered relevant in POLEmut and p53abn tumours, but remains prognostic in NSMP tumours. Its relevance is unclear in mismatch repair deficient (MMRd) EC. Using a large collection of molecularly classified EC, this study evaluated the prognostic role of FIGO grading in MMRd EC.
    METHODS: Data from three randomised trials (PORTEC-1 (n = 714); PORTEC-2 (n = 427); PORTEC-3 (n = 660)) and five clinical cohorts (n = 1357) were pooled, yielding patients with stage I-III endometrioid and non-endometrioid EC. Tumours were molecularly classified according to the 2020 WHO diagnostic algorithm, with central pathology review by an expert gynaecopathologist. Cause-specific cumulative incidence was estimated using the Aalen-Johansen method and compared using Gray's test. The independent prognostic value of FIGO grading was assessed using multivariable cause-specific Cox regression models.
    RESULTS: In total, 2621 (83.0%) of the 3158 EC cases were molecularly classified, including 730 (27.9%) MMRd tumours: 405 (55.5%) were low-grade and 325 (44.5%) were high-grade. Median follow-up was 7.2 years. Five-year cumulative incidence of overall recurrence (18.0% vs. 18.8%, p = 0.67) and cancer-specific death (12.3% vs. 14.2%; p = 0.44) did not differ between low- and high-grade MMRd EC. In multivariable analyses, corrected for age, stage, histotype, LVSI and adjuvant treatment, FIGO grading was not independently associated with overall recurrence (HR 0.83 [95%CI 0.56-1.24]; p = 0.37) or cancer-specific death (HR 0.97 [0.62-1.51]; p = 0.89).
    CONCLUSION: In conclusion, FIGO grading has no prognostic role in MMRd EC and may be omitted in risk stratification and adjuvant treatment decisions.
    Keywords:  Adjuvant therapy; Endometrial cancer; FIGO grade; Mismatch repair deficiency (MMRd); Molecular classification; Prognosis; Recurrence; Risk stratification; Survival; Treatment guidelines; Tumour grading
    DOI:  https://doi.org/10.1016/j.ejca.2026.116885
  15. Nat Genet. 2026 Jun 15.
    Decoding common and rare noncoding variant effects across cellular and developmental contexts.
    Andrew R Marderstein, Soumya Kundu, Evin M Padhi, Salil Deshpande, Austin Wang, Esther Robb, Ying Sun, Chang M Yun, Diego Pomales-Matos, Yilin Xie, Serena H Chang, Iris M Chin, Aayushi J Shah, Zachary A Gardell, M Ryan Corces, Daniel Nachun, Selin Jessa, Anshul Kundaje, Stephen B Montgomery.
      Interpreting how noncoding variants act in specific cell types across human development is a major challenge. Here we generated 3 billion predictions from deep learning sequence models of chromatin accessibility across diverse fetal and adult cellular contexts. These prioritized functional variants and revealed a dichotomy: common variants are more cell-type-specific, whereas ultra-rare variants had larger and broader effects across cell types, with the strongest evidence of purifying selection in fetal neurons. Leveraging these insights, we developed FLARE (Functional Lasso Analysis of Regulatory Evolution), which integrates evolutionary constraint to prioritize noncoding variants with extreme regulatory effects. FLARE provided a general framework for studying regulatory variation, from de novo mutations in childhood disorders to rare variants underlying outlier adult brain expression and common variants enriched for schizophrenia heritability. Together, these results demonstrate how integrating single-cell chromatin accessibility, population genetics and deep learning can identify regulatory variants that influence human development and disease.
    DOI:  https://doi.org/10.1038/s41588-026-02619-6
  16. Mol Oncol. 2026 Jun 16.
    Liquid biopsy-based diagnostic evaluation of hypermethylated CpG sites for ovarian cancer diagnosis.
    Deepa Bisht, Sameer Gupta, Amrita Chaurasia, Manisha Sachan.
      Ovarian cancer is a heterogeneous gynaecological malignancy characterised by high mortality and an absence of reliable biomarkers for detection. In this study, a CpG-specific, ARMS-PCR approach was employed to evaluate the methylation status of six diagnostically relevant CpG sites in 65 epithelial ovarian cancer tissues and 35 healthy controls. Based on methylation frequency, the top three CpG sites were selected and evaluated in two diagnostic panels. A TaqMan-based MethyLight assay incorporating cg02957270, cg00480298 and Col2A1 (as endogenous control) was developed for tissue and serum cell-free DNA cohort analysis. ARMS-PCR demonstrated diagnostic sensitivities of 80%, 73.3% and 82.3% for singleplex and multiplex panels, respectively. However, the multiplex MethyLight assay achieved 86% sensitivity and 90% specificity, with an AUC of 0.97 in the serum cohort. Furthermore, while ARMS-PCR panels displayed limited clinicopathological correlations, MethyLight showed significant correlations (P < 0.05). Overall, this pilot study highlights the promise of liquid biopsy-based diagnostics using independent hypermethylated and hypomethylated CpG biomarkers for ovarian cancer detection.
    Keywords:  ARMS‐PCR; MethyLight method; biomarker; hypermethylation; ovarian cancer
    DOI:  https://doi.org/10.1002/1878-0261.70277
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