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食管癌免疫浸润特征分析及预后生物标志物的鉴定。

Characterization of the Immune Infiltration Landscape and Identification of Prognostic Biomarkers for Esophageal Cancer.

机构信息

Department of Thoracic Surgery, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China.

Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fujian, China.

出版信息

Mol Biotechnol. 2023 Mar;65(3):361-383. doi: 10.1007/s12033-022-00526-9. Epub 2022 Jul 3.

Abstract

Immunotherapy is an effective treatment for esophageal cancer (ESCA) patients. However, there are no dependable markers for predicting prognosis and immunotherapy responses in ESCA. Our study aims to explore immune gene prognostic models and markers in ESCA as well as predictors for immunotherapy. The expression profiles of ESCA were obtained from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and International Cancer Genome Consortium (ICGC) databases. Cox regression analysis was performed to construct an immune gene prognostic model. ESCA was grouped into three immune cell infiltration (ICI) clusters by CIBERSORT algorithm. The immunotherapy response of patients in different ICI score clusters was also compared. The copy number variations, somatic mutations, and single nucleotide polymorphisms were analyzed. Enrichment analyses were also performed. An immune gene prognostic model was successfully constructed. The ICI score may be used as a predictor independent of tumor mutation burden. Enrichment analyses showed that the differentially expressed genes were mostly enriched in microvillus and the KRAS and IL6/JAK/STAT3 pathways. The top eight genes with the highest mutation frequencies in ESCA were identified and all related to the prognosis of ESCA patients. Our study established an effective immune gene prognostic model and identified markers for predicting the prognosis and immunotherapy response of ESCA patients.

摘要

免疫疗法是治疗食管癌(ESCA)患者的有效方法。然而,目前尚无可靠的标志物来预测 ESCA 的预后和免疫治疗反应。我们的研究旨在探索 ESCA 中的免疫基因预后模型和标志物,以及免疫治疗的预测因子。从癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)和国际癌症基因组联盟(ICGC)数据库中获取 ESCA 的表达谱。通过 Cox 回归分析构建免疫基因预后模型。使用 CIBERSORT 算法将 ESCA 分为三个免疫细胞浸润(ICI)聚类。还比较了不同 ICI 评分聚类患者的免疫治疗反应。分析了拷贝数变异、体细胞突变和单核苷酸多态性。还进行了富集分析。成功构建了免疫基因预后模型。ICI 评分可作为独立于肿瘤突变负担的预测因子。富集分析表明,差异表达基因主要富集在微绒毛和 KRAS 及 IL6/JAK/STAT3 通路中。确定了 ESCA 中突变频率最高的前 8 个基因,它们都与 ESCA 患者的预后相关。我们的研究建立了一个有效的免疫基因预后模型,并确定了预测 ESCA 患者预后和免疫治疗反应的标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be74/9935668/41159656a7c3/12033_2022_526_Fig1_HTML.jpg

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