关键词: Colorectal cancer (CRC) cell senescence immunotherapy tumor microenvironment (TME)

来  源:   DOI:10.21037/jgo-24-339   PDF(Pubmed)

Abstract:
UNASSIGNED: Colorectal cancer (CRC) is one of the most common cancers. Cellular senescence plays a vital role in carcinogenesis by activating many pathways. In this study, we aimed to identify biomarkers for predicting the survival and recurrence of CRC through cellular senescence-related genes.
UNASSIGNED: Utilizing The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, RNA-sequencing data and clinical information for CRC were collected. A risk model for predicting overall survival was established based on five differentially expressed genes using least absolute shrinkage and selection operator-Cox regression (LASSO-Cox regression), receiver operating characteristic (ROC), and Kaplan-Meier analyses. The study also delved into both the tumor microenvironment and the response to immunotherapy. Moreover, we gathered clinical sample data from our center in order to confirm the findings of public database analysis.
UNASSIGNED: Through ROC and Kaplan-Meier analyses, a risk model was developed using five cellular senescence-related genes [i.e., CDKN2A, SERPINE1, SNAI1, CXCL1, and ETS2] to categorize patients into high- and low-risk groups. In the TCGA-colon adenocarcinoma (COAD) and GEO-COAD cohorts, the high-risk group was associated with a bleaker forecast (P<0.05), immune cell inactivation, and insensitivity to immunotherapy in IMvigor210 database (http://research-pub.gene.com/IMvigor210CoreBiologies/). Clinical samples were then used to confirm that ETS2 and CDKN2A could serve as independent prognostic biomarkers in CRC.
UNASSIGNED: Gene signatures related to cellular senescence, specifically involving CDKN2A and ETS2, are emerging as promising biomarkers for predicting CRC prognosis and guiding immunotherapy.
摘要:
结直肠癌(CRC)是最常见的癌症之一。细胞衰老通过激活多种途径在癌变中起着至关重要的作用。在这项研究中,我们旨在通过细胞衰老相关基因鉴定预测CRC生存和复发的生物标志物.
利用癌症基因组图谱(TCGA)和基因表达综合(GEO)数据库,收集CRC的RNA测序数据和临床信息。采用最小绝对收缩和选择算子-Cox回归(LASSO-Cox回归),基于5个差异表达基因建立预测总生存期的风险模型,接收机工作特性(ROC),和Kaplan-Meier分析。该研究还深入研究了肿瘤微环境和对免疫疗法的反应。此外,我们从中心收集了临床样本数据,以确认公共数据库分析的结果.
通过ROC和Kaplan-Meier分析,使用五个细胞衰老相关基因[即,CDKN2A,SERPINE1,SNAI1,CXCL1和ETS2]将患者分为高危组和低危组。在TCGA-结肠腺癌(COAD)和GEO-COAD队列中,高危组的预测变暗(P<0.05),免疫细胞失活,和对免疫疗法的不敏感性在IMtivene210数据库(http://research-pub.gene.com/IMtivoc210CoreBiologies/)。然后使用临床样品来确认ETS2和CDKN2A可以作为CRC中的独立预后生物标志物。
与细胞衰老相关的基因特征,特别涉及CDKN2A和ETS2,正在成为预测CRC预后和指导免疫治疗的有前景的生物标志物.
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