基于免疫相关基因的模型预测结直肠癌的生存并反映各种生物学状态。
Immune-related gene-based model predicts the survival of colorectal carcinoma and reflected various biological statuses.
发表日期:2023
作者:
Zhengchun Kang, Bingchen Chen, Xiuzhu Ma, Feihu Yan, Zhen Wang
来源:
Frontiers in Molecular Biosciences
摘要:
背景:由于复杂的遗传-微环境相互作用,结直肠癌(CRC)的预后各不相同,并且强调了多种基于基因的预后模型。材料和方法:在这项工作中,开发了基于免疫相关基因表达的模型,并计算了每个样本的得分。分析模型与临床信息、免疫浸润、药物反应和生物学途径的相关性。结果:高分样本的生存期(总生存期和无进展生存期)明显长于低分样本,这在包含 1,325 个样本的 7 个数据集中进行了验证(GSE17536 (N = 115)、GSE17537 (N = 55)、GSE33113 (N = 90)、GSE37892 (N = 130)、GSE38832 (N = 74)、GSE39582 (N = 481) 和 TCGA (N = 380))。该评分与年龄和分期等临床指标显着相关,并进一步与PD-1/PD-L1基因表达相关。此外,高分样本的 APC 显着较高,MUC5B 突变率较低。高分样本显示更多的免疫浸润(包括 CD4 和 CD8 T 细胞、M1/M2 巨噬细胞和 NK 细胞)。富集通路分析表明,癌症相关通路,包括免疫相关通路,在高分样本中显着激活,并且某些药物的IC50值显着低于低分样本。结论:基于免疫相关基因开发的模型是稳健的,反映了CRC的各种状态,可能是一个潜在的临床指标。版权所有©2023 Kang,Chen,Ma,Yan和Wang。
Bakcground: Prognosis of colorectal cancer (CRC) varies due to complex genetic-microenviromental interactions, and multiple gene-based prognostic models have been highlighted. Material and Method: In this work, the immune-related genes' expression-based model was developed and the scores of each sample were calculated. The correlation between the model and clinical information, immune infiltration, drug response and biological pathways were analyzed. Results: The high-score samples have a significantly longer survival (overall survival and progression-free survival) period than those with a low score, which was validated across seven datasets containing 1,325 samples (GSE17536 (N = 115), GSE17537 (N = 55), GSE33113 (N = 90), GSE37892 (N = 130), GSE38832 (N = 74), GSE39582 (N = 481), and TCGA (N = 380)). The score is significantly associated with clinical indicators, including age and stage, and further associated with PD-1/PD-L1 gene expression. Furthermore, high-score samples have significantly higher APC and a lower MUC5B mutation rate. The high-score samples show more immune infiltration (including CD4+ and CD8+ T cells, M1/M2 macrophages, and NK cells). Enriched pathway analyses showed that cancer-related pathways, including immune-related pathways, were significantly activated in high-score samples and that some drugs have significantly lower IC50 values than those with low score. Conclusion: The model developed based on immune-related genes is robust and reflected various statuses of CRC and may be a potential clinical indicator.Copyright © 2023 Kang, Chen, Ma, Yan and Wang.