Journal article
Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma
Cancer epidemiology, biomarkers & prevention, Vol.32(4), pp.542-549
04/03/2023
DOI: 10.1158/1055-9965.EPI-22-0941
PMCID: PMC10073286
PMID: 36790339
Abstract
Better understanding of prognostic factors in tubo-ovarian high-grade serous carcinoma (HGSC) is critical, as diagnosis confers an aggressive disease course. Variation in tumor DNA methylation shows promise predicting outcome, yet prior studies were largely platform-specific and unable to evaluate multiple molecular features.
We analyzed genome-wide DNA methylation in 1,040 frozen HGSC, including 325 previously reported upon, seeking a multi-platform quantitative methylation signature that we evaluated in relation to clinical features, tumor characteristics, time to recurrence/death, extent of CD8+ tumor-infiltrating lymphocytes (TIL), gene expression molecular subtypes, and gene expression of the ATP-binding cassette transporter TAP1.
Methylation signature was associated with shorter time to recurrence, independent of clinical factors (N = 715 new set, hazard ratio (HR), 1.65; 95% confidence interval (CI), 1.10-2.46; P = 0.015; N = 325 published set HR, 2.87; 95% CI, 2.17-3.81; P = 2.2 × 10-13) and remained prognostic after adjustment for gene expression molecular subtype and TAP1 expression (N = 599; HR, 2.22; 95% CI, 1.66-2.95; P = 4.1 × 10-8). Methylation signature was inversely related to CD8+ TIL levels (P = 2.4 × 10-7) and TAP1 expression (P = 0.0011) and was associated with gene expression molecular subtype (P = 5.9 × 10-4) in covariate-adjusted analysis.
Multi-center analysis identified a novel quantitative tumor methylation signature of HGSC applicable to numerous commercially available platforms indicative of shorter time to recurrence/death, adjusting for other factors. Along with immune cell composition analysis, these results suggest a role for DNA methylation in the immunosuppressive microenvironment.
This work aids in identification of targetable epigenome processes and stratification of patients for whom tailored treatment may be most beneficial.
Details
- Title: Subtitle
- Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma
- Creators
- Chen Wang - Mayo ClinicMatthew S Block - Mayo ClinicJulie M Cunningham - Mayo Clinic in FloridaMark E Sherman - Mayo Clinic in FloridaBryan M McCauley - Mayo ClinicSebastian M Armasu - Mayo ClinicRobert A Vierkant - Mayo Clinic in FloridaNadia Traficante - Peter MacCallum Cancer CentreAline Talhouk - BC Cancer AgencySusan J Ramus - Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, New South Wales, AustraliaNadja Pejovic - Saint Louis UniversityMartin Köbel - University of CalgaryBrooke D Jorgensen - Mayo Clinic in FloridaDale W Garsed - Peter MacCallum Cancer CentreSian Fereday - Peter MacCallum Cancer CentreJennifer A Doherty - Huntsman Cancer InstituteDinuka Ariyaratne - Peter MacCallum Cancer CentreMichael S Anglesio - BC Cancer AgencyMartin Widschwendter - Universität InnsbruckTanja Pejovic - Oregon Health & Science UniversityJesus Gonzalez Bosquet - Division of Gynecologic Oncology, Department of Obstetrics and Gynecologic, University of Iowa, Iowa City, IowaDavid D Bowtell - Peter MacCallum Cancer CentreStacey J Winham - Mayo Clinic in FloridaEllen L Goode - Mayo Clinic in FloridaAustralian Ovarian Cancer Study Group
- Resource Type
- Journal article
- Publication Details
- Cancer epidemiology, biomarkers & prevention, Vol.32(4), pp.542-549
- DOI
- 10.1158/1055-9965.EPI-22-0941
- PMID
- 36790339
- PMCID
- PMC10073286
- NLM abbreviation
- Cancer Epidemiol Biomarkers Prev
- eISSN
- 1538-7755
- Grant note
- P50 CA136393 / NCI NIH HHS R01 CA172404 / NCI NIH HHS R01 CA248288 / NCI NIH HHS P30 CA015083 / NCI NIH HHS
- Language
- English
- Date published
- 04/03/2023
- Academic Unit
- Obstetrics and Gynecology
- Record Identifier
- 9984386256702771
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