Liu Yulun, Yang Jie, Han Wei, Gu Tingting, Yao Liqian, Wang Yongqiang, Chen Hua
Department of General Surgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, China.
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
Front Oncol. 2024 Jul 24;14:1409329. doi: 10.3389/fonc.2024.1409329. eCollection 2024.
Metastasis remains the leading cause of mortality among colorectal cancer (CRC) patients. Identification of new metastasis-related genes are critical to improve colorectal cancer prognosis.
Data on mRNA expression in metastatic and primary CRC was obtained from the Gene Expression Omnibus (GEO) database, including GSE81986, GSE41568, GSE71222, GSE21510, and GSE14333. Additionally, data concerning mRNA expression in colon cancer (COAD) and adjacent normal tissues were acquired from The Cancer Genome Atlas (TCGA) database. Hub genes were identified by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis. Moreover, we assessed the impact of hub gene expression on both overall survival (OS) and disease-free survival (DFS) in patients and identified ZG16 as a potential target. We generated CRC cell lines transfected with lentivirus OE-ZG16 to investigate proliferation, invasion, and migration . To further elucidate the involvement of ZG16, we utilized gene set enrichment analysis (GSEA) to identify enriched pathways, which were subsequently validated via Western blot analysis.
Five datasets containing primary and metastatic CRC samples from GEO database and CRC samples from TCGA database were included in this study and 29 hub genes were identified by WGCNA and differentially expressed gene (DEG) analysis. Low expression of the hub genes (CLCA1 and ZG16) was associated with poor DFS and OS. We confirmed the low expression of ZG16 in CRC using external database and IHC analysis at both transcriptional and protein levels. In addition, the expression of ZG16 was notably elevated in NCM460 cells in comparison to CRC cell lines. The overexpression of ZG16 in CRC cells has been shown to inhibit the proliferation, invasion, and migration of CRC cells. Furthermore, the overexpression of ZG16 has been found to suppress the activation of the epithelial-mesenchymal transition (EMT) and Wnt/β-catenin signaling pathways in CRC.
ZG16 may serve as a promising therapeutic target for metastatic CRC treatment.
转移仍然是结直肠癌（CRC）患者死亡的主要原因。鉴定新的转移相关基因对于改善结直肠癌预后至关重要。
从基因表达综合数据库（GEO）获取转移性和原发性结直肠癌中mRNA表达的数据，包括GSE81986、GSE41568、GSE71222、GSE21510和GSE14333。此外，从癌症基因组图谱（TCGA）数据库获取结肠癌（COAD）和相邻正常组织中mRNA表达的数据。通过加权基因共表达网络分析（WGCNA）和差异基因表达分析鉴定枢纽基因。此外，我们评估了枢纽基因表达对患者总生存期（OS）和无病生存期（DFS）的影响，并确定ZG16为潜在靶点。我们构建了用慢病毒OE-ZG16转染的结直肠癌细胞系，以研究其增殖、侵袭和迁移能力。为了进一步阐明ZG16的作用，我们利用基因集富集分析（GSEA）来鉴定富集的通路，随后通过蛋白质印迹分析进行验证。
本研究纳入了来自GEO数据库的包含原发性和转移性结直肠癌样本的五个数据集以及来自TCGA数据库的结直肠癌样本，并通过WGCNA和差异表达基因（DEG）分析鉴定出29个枢纽基因。枢纽基因（CLCA1和ZG16）的低表达与较差的DFS和OS相关。我们使用外部数据库和免疫组化分析在转录和蛋白质水平上证实了ZG16在结直肠癌中的低表达。此外，与结直肠癌细胞系相比，ZG16在NCM460细胞中的表达显著升高。ZG16在结直肠癌细胞中的过表达已显示出抑制结直肠癌细胞的增殖、侵袭和迁移。此外，还发现ZG16的过表达抑制了结直肠癌中上皮-间质转化（EMT）和Wnt/β-连环蛋白信号通路的激活。
ZG16可能是转移性结直肠癌治疗的一个有前景的治疗靶点。
