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KRAS 突变与结肠癌的免疫呈负相关。

KRAS mutations are negatively correlated with immunity in colon cancer.

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.

Queen Mary College, Medical Department, Nanchang University, Nanchang, Jiangxi, People's Republic of China.

出版信息

Aging (Albany NY). 2020 Nov 26;13(1):750-768. doi: 10.18632/aging.202182.

Abstract

The heterogeneity of colon cancer tumors suggests that therapeutics targeting specific molecules may be effective in only a few patients. It is therefore necessary to explore gene mutations in colon cancer. In this study, we obtained colon cancer samples from The Cancer Genome Atlas, and the International Cancer Genome Consortium. We evaluated the landscape of somatic mutations in colon cancer and found that KRAS mutations, particularly rs121913529, were frequent and had prognostic value. Using ESTIMATE analysis, we observed that the KRAS-mutated group had higher tumor purity, lower immune score, and lower stromal score than the wild-type group. Through single-sample Gene Set Enrichment Analysis and Gene Set Enrichment Analysis, we found that KRAS mutations negatively correlated with enrichment levels of tumor infiltrating lymphocytes, inflammation, and cytolytic activities. HLA gene expression and checkpoint-related genes were also lower in the KRAS-mutated group. Finally, we found 24 immune-related genes that differed in expression between the KRAS-mutated and wild-type samples, which may provide clues to the mechanism of -related immune alteration. Our findings are indicative of the prognostic and predictive value of KRAS and illustrate the relationship between KRAS mutations and immune activity in colon cancer.

摘要

结肠癌肿瘤的异质性表明,针对特定分子的治疗方法可能仅对少数患者有效。因此,有必要探索结肠癌的基因突变。在这项研究中,我们从癌症基因组图谱和国际癌症基因组联合会获得了结肠癌样本。我们评估了结肠癌体细胞突变的全景,发现 KRAS 突变,特别是 rs121913529,非常频繁且具有预后价值。通过 ESTIMATE 分析,我们观察到 KRAS 突变组的肿瘤纯度更高,免疫评分和基质评分均低于野生型组。通过单样本基因集富集分析和基因集富集分析,我们发现 KRAS 突变与肿瘤浸润淋巴细胞、炎症和细胞毒性活性的富集水平呈负相关。KRAS 突变组中 HLA 基因表达和检查点相关基因也较低。最后,我们发现 KRAS 突变和野生型样本之间有 24 个免疫相关基因表达差异,这可能为相关免疫改变的机制提供线索。我们的研究结果表明 KRAS 具有预后和预测价值,并说明了 KRAS 突变与结肠癌免疫活性之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a12/7834984/6d797760d00b/aging-13-202182-g001.jpg

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