American Association for Cancer Research
Browse
epi-22-0941_supplementary_table_6_suppst6.docx (42.79 kB)

Supplementary Table 6 from Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma

Download (42.79 kB)
journal contribution
posted on 2023-04-03, 08:21 authored by Chen Wang, Matthew S. Block, Julie M. Cunningham, Mark E. Sherman, Bryan M. McCauley, Sebastian M. Armasu, Robert A. Vierkant, Nadia Traficante, Aline Talhouk, Susan J. Ramus, Nadja Pejovic, Martin Köbel, Brooke D. Jorgensen, Dale W. Garsed, Sian Fereday, Jennifer A. Doherty, Dinuka Ariyaratne, Michael S. Anglesio, Martin Widschwendter, Tanja Pejovic, Jesus Gonzalez Bosquet, David D. Bowtell, Stacey J. Winham, Ellen L. Goode

Supplementary Table 6: Multivariate Modeling of Time to Recurrence/Death Among Studies with Gene Expression Data

Funding

National Cancer Institute (NCI)

United States Department of Health and Human Services

Find out more...

History

ARTICLE 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.

Usage metrics

    Cancer Epidemiology, Biomarkers & Prevention

    Categories

    Keywords

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC