Methylation statuses of NCOR2, PARK2, and ZSCAN12 signify densities of tumor-infiltrating lymphocytes in gastric carcinoma

Xianyu Wen, Hye Yeong Jin, Meihui Li, Younghoon Kim, Nam Yun Cho, Yoonjin Kwak, Jeong Mo Bae, Hye Seung Lee, Gyeong Hoon Kang

Research output: Contribution to journalArticlepeer-review

Abstract

Individual cell types of human tissues have their own CpG site methylation profiles, which might be utilized for the development of methylation markers to denote tumor-infiltrating lymphocytes (TILs). We aimed to develop DNA methylation markers that recapitulate the densities of TILs in gastric carcinoma (GC). Through genome-wide methylation profiling, NCOR2, PARK2, and ZSCAN12 were found to be highly methylated in CD3-positive and CD8-positive cells and rarely methylated in tumor cells. Scores of the three methylation markers were analyzed for their relationship with the overall survival and recurrence-free survival of patients with advanced GC (n = 471). The scores of three methylation markers were closely associated with densities of CD3-positive or CD8-positive cells at the tumor center or invasive front of GCs and found to be a significant prognostic factor in univariate analysis of overall survival and recurrence-free survival. In multivariate analysis, the highest score showed hazard ratios of 0.513 (CI 0.306–0.857) and 0.434 (CI 0.261–0.720) for overall survival and recurrence-free survival, respectively. The findings suggest that methylation markers signifying TILs might be utilized for the recapitulation of TIL density in GCs and serve as biomarkers for predicting prognosis in patients with GC.

Original languageEnglish
Article number862
JournalScientific Reports
Volume12
Issue number1
DOIs
StatePublished - Dec 2022

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