Ma Lixing, Song Kang, Zang Jinfeng
Department of Surgery, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
Department of Hepatobiliary Surgery, Taixing People's Hospital, The Affiliated Taixing People's Hospital of Yangzhou University, Taixing, Jiangsu 225400, P.R. China.
Exp Ther Med. 2023 Sep 28;26(5):532. doi: 10.3892/etm.2023.12231. eCollection 2023 Nov.
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and a major cause of cancer mortality worldwide. Integrin β5 (ITGB5) is considered to be involved in the intercellular signal transduction and regulation of tumorigenesis and development. The present study investigated the association between ITGB5 expression levels and the prognosis of ICC, as well as the effects of ITGB5 on the proliferation and invasion of ICC cells. RNA-sequencing transcriptomic profiling data of ICC samples were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Tissue specimens from patients with ICC treated at Taizhou People's Hospital were collected and the ITGB5 expression levels were evaluated using immunohistochemical staining. The biological function of ITGB5 in ICC was investigated using Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA) and experiments using HuCCT1 cells. After knocking down ITGB5 expression, cell proliferation was detected using Cell Counting Kit-8 assay, while cell invasion was assessed using Transwell assays. According to TCGA dataset, ITGB5 was highly expressed in ICC; however, there was no significant difference in prognosis between patients with high and low ITGB5 expression levels. High expression of ITGB5 was present in the tissues of patients with ICC from the GEO database, which was associated with poor prognosis. Survival analyses of the clinical data obtained in the present study revealed that high expression levels of ITGB5 in patients with ICC were associated with a reduced overall survival. GO and GSEA indicated that genes associated with ITGB5 were enriched in the extracellular matrix-receptor interaction and focal adhesion signaling pathways. Silencing ITGB5 inhibited the proliferation and invasion of ICC cells. In conclusion, ITGB5 may act as an essential regulator of ICC development and progression by influencing the proliferation and invasion of ICC cells. However, future studies with larger sample sizes are required to validate the role of ITGB5 in the prognosis of patients with ICC.
肝内胆管癌（ICC）是全球第二常见的原发性肝癌，也是癌症死亡的主要原因。整合素β5（ITGB5）被认为参与细胞间信号转导以及肿瘤发生和发展的调控。本研究调查了ITGB5表达水平与ICC预后之间的关联，以及ITGB5对ICC细胞增殖和侵袭的影响。从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中检索ICC样本的RNA测序转录组分析数据。收集在泰州市人民医院接受治疗的ICC患者的组织标本，并使用免疫组织化学染色评估ITGB5表达水平。利用基因本体论（GO）、基因集富集分析（GSEA）以及使用HuCCT1细胞进行实验，研究ITGB5在ICC中的生物学功能。敲低ITGB5表达后，使用细胞计数试剂盒-8法检测细胞增殖，同时使用Transwell法评估细胞侵袭。根据TCGA数据集，ITGB5在ICC中高表达；然而，ITGB5表达水平高和低的患者在预后方面没有显著差异。来自GEO数据库的ICC患者组织中存在ITGB5高表达，这与预后不良相关。对本研究中获得的临床数据进行生存分析显示，ICC患者中ITGB5高表达与总生存期缩短相关。GO和GSEA表明，与ITGB5相关的基因在细胞外基质-受体相互作用和粘着斑信号通路中富集。沉默ITGB5可抑制ICC细胞的增殖和侵袭。总之，ITGB5可能通过影响ICC细胞的增殖和侵袭，作为ICC发生发展的重要调节因子。然而，需要未来更大样本量的研究来验证ITGB5在ICC患者预后中的作用。
