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与结直肠癌中CD4 +和CD8 + T细胞浸润相关的免疫预后指数的开发与验证

Development and Validation of an Immune Prognostic Index Related to Infiltration of CD4+ and CD8+ T Cells in Colorectal Cancer.

作者信息

Chen Chengru, Zou Peng, Wu Xiaobin

机构信息

Department of Gastrointestinal Surgery, The Eighth Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Shenzhen, 518033, Guangdong Province, China.

出版信息

Mol Biotechnol. 2024 Jul 18. doi: 10.1007/s12033-024-01237-z.

DOI:10.1007/s12033-024-01237-z
PMID:39026041
Abstract

Colorectal cancer (CRC) is a highly prevalent cancer worldwide, but treatment outcomes can vary significantly among patients with similar clinical or historical stages. This study aimed to investigate the differences in immune cell abundance associated with malignant progression in CRC patients. We utilized data from patients with CRC obtained from The Cancer Genome Atlas as our training set. To assess immune cell infiltration levels, an immune cell risk score (ICRS) was calculated. Furthermore, we performed network analysis to identify effective T cell-related genes (ETRGs) and subsequently constructed an effective T cell prognostic index (ETPI). The performance of the ETPI was evaluated through external validation using four Gene Expression Omnibus datasets. Additionally, a nomogram analysis and drug sensitivity analysis were conducted to explore the clinical utility of the ETRGs. We also examined the expression of ETRGs in clinical samples. Based on the ICRS, we identified activated CD4+ and CD8+ T cells as protective factors in terms of prognosis. Six ETRGs were identified to develop the ETPI, which exhibited remarkable prognostic performance. In the external validation of immunotherapy, the low ETPI group demonstrated a significantly lower recurrence rate. To optimize therapeutic strategies, we developed a nomogram. Notably, patients with different ETPI values exhibited varying responses to tumor pathway inhibitors. Finally, we observed higher protein expression of certain ETRGs in normal tissues compared to tumors. Our findings suggest that the ETPI may contribute to the precise selection of patients based on tumor microenvironment and key genomic landscape interactions, thereby optimizing drug benefits and informing clinical strategies in future.

摘要

结直肠癌(CRC)是全球范围内一种高度流行的癌症,但在临床或历史分期相似的患者中,治疗结果可能存在显著差异。本研究旨在调查结直肠癌患者中与恶性进展相关的免疫细胞丰度差异。我们利用从癌症基因组图谱获得的结直肠癌患者数据作为训练集。为了评估免疫细胞浸润水平,计算了免疫细胞风险评分(ICRS)。此外,我们进行了网络分析以确定有效的T细胞相关基因(ETRG),随后构建了有效的T细胞预后指数(ETPI)。通过使用四个基因表达综合数据集进行外部验证来评估ETPI的性能。此外,进行了列线图分析和药物敏感性分析,以探索ETRG的临床应用。我们还检查了ETRG在临床样本中的表达。基于ICRS,我们确定活化的CD4 +和CD8 + T细胞在预后方面是保护因素。确定了六个ETRG来构建ETPI,其具有显著的预后性能。在免疫治疗的外部验证中,低ETPI组的复发率显著较低。为了优化治疗策略,我们开发了一个列线图。值得注意的是,不同ETPI值的患者对肿瘤通路抑制剂表现出不同的反应。最后,我们观察到与肿瘤相比,某些ETRG在正常组织中的蛋白表达更高。我们的研究结果表明,ETPI可能有助于根据肿瘤微环境和关键基因组景观相互作用精确选择患者,从而优化药物疗效并为未来的临床策略提供信息。

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