Wang Bingyu, Du Zifei, Lin ChongSen, Liu Dandan, Guo Jiewen, Shi Jiawei, Wang Xiaobo
Department of Science and Education, The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Orthopedics, Huizhou Hospital of Guangzhou University of Chinese Medicine, Huicheng, Guangdong, China.
Heliyon. 2024 Apr 24;10(9):e30244. doi: 10.1016/j.heliyon.2024.e30244. eCollection 2024 May 15.
The integrator subunit (INTS) family, a group exclusive to metazoans, participates in various biologic processes. However, their roles in hepatocellular carcinoma (HCC) remain largely unexplored.
Public databases were utilized to investigate the transcriptional and protein expression, and clinical relevance of the INTS family in HCC. Meanwhile, the effects of INTS13 knockdown and overexpression on cell proliferation and apoptosis were studied using HCC cell lines.
The mRNA expression of most INTSs were higher in tumor than normal tissues. Higher expression of INTS1/2/3/4/7/8/9/11/12/13 were correlated with poorer overall survival (OS) in Kaplan-Meier Survival Analysis. Multivariate analysis revealed higher level of INTS13 was an independent prognostic factor for shorter OS. Furthermore, genetic alteration of INTS3/6/7/8/9/10 were found in HCC patients and was associated with shorter disease-free survival and progression-free survival. INTS1/2/3/5/7/11/13/14 were associated with activation of tumor-induced immune response and immune infiltration in HCC. Knockdown of INTS13 inhibited cell proliferation and induced apoptosis in HCC cell lines, while overexpression of INTS13 had the opposite effect.
Our results indicate that INTS13 is an independent prognostic biomarker in HCC. Furthermore, INTS13 enhances cell proliferation and decreases cell apoptosis in HCC cell lines leading to a poorer OS in HCC patients.
整合器亚基（INTS）家族是后生动物特有的一组蛋白，参与多种生物学过程。然而，它们在肝细胞癌（HCC）中的作用在很大程度上仍未得到探索。
利用公共数据库研究INTS家族在HCC中的转录和蛋白表达以及临床相关性。同时，使用HCC细胞系研究INTS13基因敲低和过表达对细胞增殖和凋亡的影响。
大多数INTS在肿瘤组织中的mRNA表达高于正常组织。在Kaplan-Meier生存分析中，INTS1/2/3/4/7/8/9/11/12/13的高表达与较差的总生存期（OS）相关。多变量分析显示，INTS13的高水平是OS缩短的独立预后因素。此外，在HCC患者中发现INTS3/6/7/8/9/10存在基因改变，且与无病生存期和无进展生存期缩短相关。INTS1/2/3/5/7/11/13/14与HCC中肿瘤诱导的免疫反应激活和免疫浸润相关。敲低INTS13可抑制HCC细胞系的细胞增殖并诱导凋亡，而INTS13过表达则产生相反的效果。
我们的结果表明，INTS13是HCC中的一个独立预后生物标志物。此外，INTS13增强HCC细胞系中的细胞增殖并减少细胞凋亡，导致HCC患者的OS较差。
