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神经功能基因的异常甲基化是结直肠癌发生和发展的一个标志。

Aberrant methylation in neurofunctional gene serves as a hallmark of tumorigenesis and progression in colorectal cancer.

机构信息

Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Guangdong Institute of Gastroenterology, Guangzhou, Guangdong, China.

出版信息

BMC Cancer. 2023 Apr 6;23(1):315. doi: 10.1186/s12885-023-10765-x.

DOI:10.1186/s12885-023-10765-x
PMID:37020199
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10077670/
Abstract

BACKGROUND

DNA methylation is one of the most promising biomarkers in predicting the prognosis of colorectal cancer (CRC). We aimed to develop a DNA methylation biomarker that could evaluate the prognosis of CRC.

METHODS

A promising DNA methylation biomarker was developed by hypermethylated genes in cancer tissue that were identified from Illumina EPIC methylation arrays. A cohort comprising 30 pairs of snap-frozen tumor tissue and adjacent normal tissue was used for correlation analysis between the methylation and expression status of the marker. The other cohort comprising 254 formalin-fixed paraffin-embedded (FFPE) tumor tissue from 254 CRC patients was used for prognosis analysis.

RESULTS

Regulating synaptic membrane exocytosis 2 (RIMS2) was hypermethylated and lowly expressed in CRC comparing to adjacent normal tissue. Hypermethylation of RIMS2 in CRC was correlated with less frequent KRAS mutant and high differentiation. RIMS2 promoter methylation showed independent predictive value for survival outcome (P = 0.015, HR 1.992, 95% CI [(1.140-3.48)]), and a combination of RIMS2 methylation with KRAS status could predict prognosis better.

CONCLUSIONS

RIMS2 is frequently hypermethylated in CRC, which can silence the expression of RIMS2. RIMS2 methylation is a novel biomarker for predicting the prognosis of CRC.

摘要

背景

DNA 甲基化是预测结直肠癌（CRC）预后最有前途的生物标志物之一。我们旨在开发一种 DNA 甲基化生物标志物，以评估 CRC 的预后。

方法

通过在 Illumina EPIC 甲基化阵列中鉴定出的癌症组织中高甲基化基因，开发了一种有前途的 DNA 甲基化生物标志物。使用包括 30 对冷冻肿瘤组织和相邻正常组织的队列进行标记物的甲基化和表达状态之间的相关性分析。另一个队列包括 254 例来自 254 例 CRC 患者的福尔马林固定石蜡包埋（FFPE）肿瘤组织，用于预后分析。

结果

与相邻正常组织相比，调节突触膜胞吐 2（RIMS2）在 CRC 中呈高甲基化和低表达。CRC 中 RIMS2 的高甲基化与 KRAS 突变频率较低和高分化相关。RIMS2 启动子甲基化对生存结果具有独立的预测价值（P=0.015，HR 1.992，95%CI [1.140-3.48]），并且 RIMS2 甲基化与 KRAS 状态的组合可以更好地预测预后。

结论

RIMS2 在 CRC 中经常发生高甲基化，这可能会沉默 RIMS2 的表达。RIMS2 甲基化是预测 CRC 预后的一种新的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115a/10077670/5c4550a080b1/12885_2023_10765_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115a/10077670/56f8e37461ef/12885_2023_10765_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115a/10077670/cefea4b5091c/12885_2023_10765_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115a/10077670/a05c30f876f1/12885_2023_10765_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115a/10077670/5c4550a080b1/12885_2023_10765_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115a/10077670/56f8e37461ef/12885_2023_10765_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115a/10077670/cefea4b5091c/12885_2023_10765_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115a/10077670/a05c30f876f1/12885_2023_10765_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/115a/10077670/5c4550a080b1/12885_2023_10765_Fig4_HTML.jpg

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