Ye Qiuwen, Zhou Tao, Liu Xin, Chen Dong, Yang Burong, Yu Tingdong, Tan Jing
Department of Hepatobiliary and Pancreatic Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Kunming, China.
Department of Hepato-Pancreato-Biliary Surgery, First People's Hospital of Kunming City & Calmette Affiliated Hospital of Kunming Medical University, Kunming, China.
J Gastrointest Oncol. 2024 Oct 31;15(5):2286-2304. doi: 10.21037/jgo-24-612. Epub 2024 Oct 29.
Pancreatic adenocarcinoma (PAAD) is a highly aggressive malignant tumor with a poor prognosis. Integrin subunit genes (ITGs) serve as biomarkers for various types of cancers; however, to date, no prognostic research has been conducted on the ITGs in PAAD. This study aims to fill this gap by investigating the role of ITGs in PAAD prognosis.
RNA-sequencing data, clinicopathological features, and survival information from The Cancer Genome Atlas (TCGA) database were sourced via GTEx. The GSE62452 data set was acquired from the Gene Expression Omnibus (GEO) database. A single-sample gene set enrichment analysis (ssGSEA) was first conducted to classify the PAAD samples from TCGA and GEO data sets with different ITG scores. A differential analysis was employed to identify the differentially expressed genes (DEGs) between the normal and PAAD samples, and between the high and low ITG score groups in both TCGA and GEO data sets.
A total of 22 key differentially expressed ITGs (KDE-ITGs) were identified and enriched in eight Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, focal adhesion, and the extracellular matrix (ECM)-receptor interaction. A prognostic model comprising the eight KDE-ITGs was established. Additionally, 2,371 DEGs were found between the high- and low-risk groups, which were mainly enriched in the Gene Ontology (GO) terms of cell morphogenesis and cytokine production, and KEGG pathways such as necroptosis, lysosome, and ferroptosis. Further, the proportions of T cells and cluster of differentiation 8 (CD8) T cells, and the expression levels of immune checkpoints, such as cluster of differentiation 274 (CD274) and lymphocyte activating gene 3 (LAG3), differed significantly between the two risk groups.
The eight identified KDE-ITGs in PAAD were used to establish a new prognosis model, which might have clinical application, especially in immunotherapy.
胰腺腺癌（PAAD）是一种侵袭性很强的恶性肿瘤，预后较差。整合素亚基基因（ITGs）可作为多种癌症的生物标志物；然而，迄今为止，尚未对PAAD中的ITGs进行预后研究。本研究旨在通过调查ITGs在PAAD预后中的作用来填补这一空白。
通过GTEx获取来自癌症基因组图谱（TCGA）数据库的RNA测序数据、临床病理特征和生存信息。GSE62452数据集从基因表达综合数据库（GEO）获得。首先进行单样本基因集富集分析（ssGSEA），以根据不同的ITG评分对来自TCGA和GEO数据集的PAAD样本进行分类。采用差异分析来鉴定正常样本与PAAD样本之间以及TCGA和GEO数据集中高ITG评分组与低ITG评分组之间的差异表达基因（DEGs）。
共鉴定出22个关键差异表达的ITGs（KDE-ITGs），并在八个京都基因与基因组百科全书（KEGG）途径中富集，包括磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）信号通路、粘着斑和细胞外基质（ECM）-受体相互作用。建立了一个包含八个KDE-ITGs的预后模型。此外，在高风险组和低风险组之间发现了2371个DEGs，这些DEGs主要富集在细胞形态发生和细胞因子产生的基因本体（GO）术语以及坏死性凋亡、溶酶体和铁死亡等KEGG途径中。此外，两个风险组之间T细胞和分化簇8（CD8）T细胞的比例以及免疫检查点如分化簇274（CD274）和淋巴细胞激活基因3（LAG3）的表达水平存在显著差异。
在PAAD中鉴定出的八个KDE-ITGs被用于建立一个新的预后模型，该模型可能具有临床应用价值，尤其是在免疫治疗方面。
