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

• Published in: Scientific reports 2022-01, Vol.12 (1), p.862-862, Article 862
• Main Authors: Wen, Xianyu, Jin, Hye-Yeong, Li, Meihui, Kim, Younghoon, Cho, Nam-Yun, Kwak, Yoonjin, Bae, Jeong Mo, Lee, Hye Seung, Kang, Gyeong Hoon
• Format: Article
• Language: English
• Subjects: 692/4017; 692/4020; 692/4028; Biomarkers - metabolism; Carcinoma - genetics; Carcinoma - mortality; Carcinoma - pathology; CD3 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - metabolism; CpG islands; DNA methylation; DNA Methylation - genetics; Female; Forecasting; Gastric cancer; Genomes; Humanities and Social Sciences; Humans; Invasiveness; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Lymphocytes; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Male; Medical prognosis; Middle Aged; multidisciplinary; Multivariate analysis; Nuclear Receptor Co-Repressor 2 - genetics; Nuclear Receptor Co-Repressor 2 - metabolism; Prognosis; Science; Science (multidisciplinary); Stomach Neoplasms - genetics; Stomach Neoplasms - mortality; Stomach Neoplasms - pathology; Survival; Survival Rate; Tumor cells; Tumor Microenvironment - genetics; Tumor-infiltrating lymphocytes; Tumors; Ubiquitin-Protein Ligases - genetics; Ubiquitin-Protein Ligases - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-04797-9

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.