Zhang Yuanyuan, Yang Feng, Peng Xiaohong, Li Xiaoyu, Luo Na, Zhu Wenjun, Fu Min, Li Qianxia, Hu Guangyuan
Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Cell Dev Biol. 2021 Apr 20;9:665364. doi: 10.3389/fcell.2021.665364. eCollection 2021.
Hypoxia is a common phenomenon in solid tumors, which plays an important role in tumor proliferation, apoptosis, angiogenesis, invasion and metastasis, energy metabolism and chemoradiotherapy resistance. However, comprehensive analysis of hypoxia markers in colorectal adenocarcinoma (COAD) is still lacking. And there is a need for mechanism exploration and clinical application. The gene expression, mutation and clinical data of COAD were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. Tumor samples from TCGA were randomly divided into the training and internal validation groups, while tumor samples from GEO were used as the external validation group. Univariate COX-LASSO-multivariate COX method was applied to construct the prognostic model. We clustered all TCGA tumor samples into high, medium and low hypoxia groups, evaluated the correlation between hypoxia degree and immunoactivity, and explored the combined effect of mutation for common target genes and model riskscore on survival in COAD patients. Finally, we developed a dynamic nomograph App online for direct clinical application and carried out multiple validations of the prognostic model. Our hypoxia-related prognostic model for COAD patients is accurate and has been successfully validated internally and externally. Single Sample Gene Set Enrichment Analysis (ssGSEA) and Gene Set Enrichment Analysis (GSEA) results suggest that for COAD patients with higher hypoxia, the stronger the associated immunosuppressive activity, providing a possible mechanism for the lower survival rate. Finally, the dynamic nomograph App online enhances the clinical translational significance of the study. In this study, an accurate prognostic model for COAD patients was established and validated. In addition, our innovative findings include correlations between hypoxia levels and immune activity, as well as an in-depth exploration of common target gene mutations.
缺氧是实体瘤中的常见现象，在肿瘤增殖、凋亡、血管生成、侵袭和转移、能量代谢及放化疗耐药中起重要作用。然而，仍缺乏对结直肠癌（COAD）缺氧标志物的综合分析，且需要进行机制探索和临床应用。分别从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）下载COAD的基因表达、突变及临床数据。将TCGA的肿瘤样本随机分为训练组和内部验证组，而将GEO的肿瘤样本用作外部验证组。应用单因素COX-LASSO-多因素COX方法构建预后模型。我们将所有TCGA肿瘤样本聚类为高、中、低缺氧组，评估缺氧程度与免疫活性之间的相关性，并探讨常见靶基因突变及模型风险评分对COAD患者生存的联合影响。最后，我们开发了一个在线动态列线图应用程序以供直接临床应用，并对预后模型进行了多次验证。我们为COAD患者建立的缺氧相关预后模型准确，已成功进行内部和外部验证。单样本基因集富集分析（ssGSEA）和基因集富集分析（GSEA）结果表明，对于缺氧程度较高的COAD患者，其相关免疫抑制活性越强，这为较低的生存率提供了一种可能的机制。最后，在线动态列线图应用程序增强了该研究的临床转化意义。在本研究中，建立并验证了一个针对COAD患者的准确预后模型。此外，我们的创新性发现包括缺氧水平与免疫活性之间的相关性，以及对常见靶基因突变的深入探索。
