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NCOR2、PARK2 和 ZSCAN12 的甲基化状态提示胃癌中 TIL(肿瘤浸润淋巴细胞)的密度

英文原题:Methylation statuses of NCOR2, PARK2, and ZSCAN12 signify densities of tumor-infiltrating lymphocytes in gastric carcinoma.

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

PubMed 2022/01/17(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

人体不同细胞类型具有各自的CpG位点甲基化谱,可用于开发反映TIL(肿瘤浸润淋巴细胞)的甲基化标志物。本研究旨在开发能够重现胃癌(GC)TIL密度的DNA甲基化标志物。通过全基因组甲基化谱分析发现,NCOR2、PARK2和ZSCAN12在CD3阳性及CD8阳性细胞中高度甲基化,而在肿瘤细胞中很少甲基化。研究分析了471例晚期GC患者上述三种甲基化标志物评分与总生存期及无复发生存期的关系。三种标志物评分与胃癌肿瘤中心或浸润前沿的CD3阳性或CD8阳性细胞密度密切相关;单因素分析显示其为总生存期和无复发生存期的显著预后因素。多因素分析中,最高评分对应总生存期和无复发生存期的风险比分别为0.513(置信区间0.306–0.857)和0.434(置信区间0.261–0.720)。研究结果提示,反映TIL的甲基化标志物可用于重现GC中的TIL密度,并作为预测GC患者预后的生物标志物。

展开英文摘要原文

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.

论文信息

作者
Wen X、Jin HY、Li M、Kim Y、Cho NY、Kwak Y、Bae JM、Lee HS
第一作者单位
Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.South Korea
通讯作者单位
Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Korea. ghkang@snu.ac.kr.South Korea
文献类型
非美国政府资助研究
期刊
Scientific reports2022 Jan 17
原文标识
PubMed 35039565 · DOI 10.1038/s41598-022-04797-9