Department of Hepatobiliary and Pancreatic Surgery, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
Geriatric Medicine Center, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China.
Cancer Immunol Immunother. 2023 Mar;72(3):647-664. doi: 10.1007/s00262-022-03269-3. Epub 2022 Aug 29.
CD8 + T lymphocytes are immune cells that play a crucial anti-tumor role in the human body, and prognostic value of CD8 + T cell-related regulatory genes in PAAD remains elusive. Data on 179 expression profiles across 13 immune cell datasets were downloaded from the GEO database, and the expression profiles of CD8 + T cell-related genes were obtained using WGCNA. Molecular subtypes based on CD8 + T cell-related genes were constructed using the ConsensusClusterPlus algorithm. Lasso regression analysis was performed to build a 10-gene signature. GSVA was performed to explore the pathways related to these ten genes. The IMvigor210 cohort was used to explore the predictive efficacy of the signature in terms of immunotherapy response. Four hundred and forty-six CD8 + T cell-related genes were obtained. One hundred and nine genes in TCGA and GEO datasets were closely related to the prognosis of patients and were included in the next study. PAAD samples were divided into two subtypes (IC1 and IC2) according to consensus cluster analysis. These two immune subtypes were significantly different in terms of immune checkpoint genes, immune function, and drug treatment response. Additionally, the 10-gene signature constructed based on CD8 + T cell-related genes showed a stable prognostic performance in TCGA and GEO cohorts. Moreover, it served as an independent prognostic factor for patients with PAAD. Furthermore, the 10-gene signature could effectively predict the response to immunotherapy. The immunophenotyping-derived prognostic model based on CD8 T cell-related genes provides a basis for the clinical treatment of pancreatic cancer.
CD8+T 淋巴细胞是人体中发挥重要抗肿瘤作用的免疫细胞，CD8+T 细胞相关调节基因在胰腺导管腺癌（PAAD）中的预后价值仍不清楚。从 GEO 数据库中下载了 179 个涵盖 13 个免疫细胞数据集的表达谱数据，并使用 WGCNA 获得了 CD8+T 细胞相关基因的表达谱。使用 ConsensusClusterPlus 算法构建基于 CD8+T 细胞相关基因的分子亚型。使用 Lasso 回归分析构建 10 基因特征。进行 GSVA 以探索与这 10 个基因相关的途径。使用 IMvigor210 队列探索该特征在免疫治疗反应方面的预测效果。获得了 446 个 CD8+T 细胞相关基因。TCGA 和 GEO 数据集的 109 个基因与患者的预后密切相关，并纳入下一步研究。根据共识聚类分析，将 PAAD 样本分为两种亚型（IC1 和 IC2）。这两种免疫亚型在免疫检查点基因、免疫功能和药物治疗反应方面存在显著差异。此外，基于 CD8+T 细胞相关基因构建的 10 基因特征在 TCGA 和 GEO 队列中表现出稳定的预后性能。此外，它是 PAAD 患者的独立预后因素。此外，该 10 基因特征可有效预测免疫治疗的反应。基于 CD8 T 细胞相关基因的免疫表型预后模型为胰腺癌的临床治疗提供了依据。
