Lin Youyu, Zhong Wenting, Lin Qili, Ye Yan, Li Shengzhao, Chen Hui, Liu Hongxia, Xu Luyun, Zhuang Wei, Chen Shaoqing, Lin Yao, Wang Qingshui
The Second Affiliated Hospital of Fujian Traditional Chinese Medical University, Fujian-Macao Science and Technology Cooperation Base of Traditional Chinese Medicine-Oriented Chronic Disease Prevention and Treatment, Innovation and Transformation Center, Fujian University of Traditional Chinese Medicine Fuzhou, Fujian, China.
College of Life Sciences, Fujian Normal University Fuzhou, Fujian, China.
Am J Cancer Res. 2023 Jun 15;13(6):2269-2284. eCollection 2023.
Liver cancer is a prevalent type of tumor worldwide. CRISPR-Cas9 technology can be utilized to identify therapeutic targets for novel therapeutic approaches. In this study, our goal was to identify key genes related to the survival of hepatocellular carcinoma (HCC) cells by analyzing the DepMap database based on CRISPR-Cas9. We screened candidate genes associated with HCC cell survival and proliferation from DepMap and identified their expression levels in HCC from the TCGA database. To develop a prognostic risk model based on these candidate genes, we performed WGCNA, functional pathway enrichment analysis, protein interaction network construction, and LASSO analysis. Our findings show that 692 genes were critical for HCC cell proliferation and survival, and among them, 571 DEGs were identified in HCC tissues. WGCNA categorized these 584 genes into three modules, and the blue module consisting of 135 genes was positively linked to the tumor stage. Using the MCODE approach in Cytoscape, we identified ten hub genes in the PPI network, and through Cox univariate analysis and Lasso analysis, we developed a prognostic model consisting of three genes (SFPQ, SSRP1, and KPNB1). Furthermore, knocking down SFPQ inhibited HCC cell proliferation, migration, and invasion. In conclusion, we identified three core genes (SFPQ, SSRP1, and KPNB1) that are essential for the proliferation and survival of HCC cells. These genes were used to develop a prognostic risk model, and knockdown of SFPQ was found to inhibit the proliferation, migration, and invasion of HCC cells.
肝癌是全球范围内一种常见的肿瘤类型。CRISPR - Cas9技术可用于识别新型治疗方法的治疗靶点。在本研究中，我们的目标是通过基于CRISPR - Cas9分析DepMap数据库来识别与肝细胞癌（HCC）细胞存活相关的关键基因。我们从DepMap中筛选了与HCC细胞存活和增殖相关的候选基因，并从TCGA数据库中确定了它们在HCC中的表达水平。为了基于这些候选基因开发一个预后风险模型，我们进行了加权基因共表达网络分析（WGCNA）、功能通路富集分析、蛋白质相互作用网络构建和套索分析（LASSO）。我们的研究结果表明，692个基因对HCC细胞增殖和存活至关重要，其中在HCC组织中鉴定出571个差异表达基因（DEGs）。WGCNA将这584个基因分为三个模块，由135个基因组成的蓝色模块与肿瘤分期呈正相关。使用Cytoscape中的分子复合物检测（MCODE）方法，我们在蛋白质 - 蛋白质相互作用（PPI）网络中鉴定出10个枢纽基因，并通过Cox单变量分析和套索分析，我们开发了一个由三个基因（SFPQ、SSRP1和KPNB1）组成的预后模型。此外，敲低SFPQ可抑制HCC细胞的增殖、迁移和侵袭。总之，我们鉴定出三个对HCC细胞增殖和存活至关重要的核心基因（SFPQ、SSRP1和KPNB1）。这些基因被用于开发一个预后风险模型，并且发现敲低SFPQ可抑制HCC细胞的增殖、迁移和侵袭。
