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食管鳞状细胞癌中一种预后免疫相关基因特征的鉴定与验证

Identification and Validation of a Prognostic Immune-Related Gene Signature in Esophageal Squamous Cell Carcinoma.

作者信息

Xiong Kai, Tao Ziyou, Zhang Zeyang, Wang Jianyao, Zhang Peng

机构信息

Department of Cardiovascular Thoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.

Department of Thoracic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Bioeng Biotechnol. 2022 Apr 13;10:850669. doi: 10.3389/fbioe.2022.850669. eCollection 2022.

Abstract

Esophageal carcinoma (EC) is a common malignant cancer worldwide. Esophageal squamous cell carcinoma (ESCC), the main type of EC, is difficult to treat because of the widespread morbidity, high fatality rates, and low quality of life caused by postoperative complications and no specific molecular target. In this study, we screened genes to establish a prognostic model for ESCC. The transcriptome expression profiles of 81 ESCC tissues and 340 normal esophageal mucosal epithelium tissues were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) cohorts. The transcriptome expression datasets of 19 esophageal squamous carcinoma cell lines were downloaded from Cancer Cell Line Encyclopedia (CCLE). The R software Limma package was used to identify 6,231 differentially expressed genes and 647 differentially expressed immune-related genes between normal and ESCC tissues. Gene functional analysis was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Weighted gene co-expression network analysis (WGCNA) was used to screen out 18 immune-related prognostic genes. We then established the prognostic and risk signature using these genes, and the patients were divided into low-risk and high-risk groups. Compared with high-risk group patients, the low-risk group patients had longer overall survival. M1 macrophages and resting dendritic cells were differentially distributed between the low-risk and high-risk groups and were related to patient survival. We also examined the functional immune cell and immune molecule levels in low-risk and high-risk group patients, with significant differences in the tumor microenvironment between the two groups. To further verify the accuracy of the prognostic risk model, we performed area under the ROC curve (AUC) analysis. The AUC value was 0.931 for the prognostic risk, which was better than the microsatellite instability (MSI) and Tumor Immune Dysfunction and Exclusion (TIDE) scores. In conclusion, we found 18 immune-related prognostic genes related to the occurrence of ESCC and established a prognostic model for predicting disease severity.

摘要

食管癌(EC)是全球常见的恶性肿瘤。食管鳞状细胞癌(ESCC)是EC的主要类型,由于其发病率高、死亡率高以及术后并发症导致生活质量低且缺乏特异性分子靶点,治疗困难。在本研究中,我们筛选基因以建立ESCC的预后模型。从癌症基因组图谱(TCGA)和基因型组织表达(GTEx)队列中获得了81例ESCC组织和340例正常食管黏膜上皮组织的转录组表达谱。从癌症细胞系百科全书(CCLE)下载了19个食管鳞状癌细胞系的转录组表达数据集。使用R软件的Limma包来鉴定正常组织与ESCC组织之间的6231个差异表达基因和647个差异表达的免疫相关基因。使用基因本体论(GO)和京都基因与基因组百科全书(KEGG)进行基因功能分析。加权基因共表达网络分析(WGCNA)用于筛选出18个免疫相关的预后基因。然后我们使用这些基因建立了预后和风险特征,并将患者分为低风险和高风险组。与高风险组患者相比,低风险组患者的总生存期更长。M1巨噬细胞和静息树突状细胞在低风险和高风险组之间分布不同,且与患者生存相关。我们还检测了低风险和高风险组患者的功能性免疫细胞和免疫分子水平,两组之间的肿瘤微环境存在显著差异。为了进一步验证预后风险模型的准确性,我们进行了ROC曲线下面积(AUC)分析。预后风险的AUC值为0.931,优于微卫星不稳定性(MSI)和肿瘤免疫功能障碍与排除(TIDE)评分。总之,我们发现了18个与ESCC发生相关的免疫相关预后基因,并建立了一个预测疾病严重程度的预后模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddf/9043362/95ffc2c323fc/fbioe-10-850669-g001.jpg

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