Li Xueting, Zhao Yongzheng, Lu Jin, Sun Junpei, Zhang Yan, Du Danli
Department of Obstetrics and Gynecology, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
Department of Human Anatomy, Bengbu Medical University, Bengbu 233030, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2024 Oct;40(10):909-917.
Objective To screen for the key genes involved in the development of ovarian cancer (OV), analyze the immune cell infiltration and construct a risk model, so as to provide evidence for the early diagnosis, treatment and prognosis evaluation of OV patients. Methods The GSE18520 and GSE6008 datasets were analyzed for differentially expressed genes (DEGs) using the GEO2R data analysis tool, and a Venn diagram was generated. Then, DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) networks, as well as mutations, expression and prognosis analysis to identify key genes. Next, a risk model was constructed and immune cell infiltration analysis of key genes was performed. Finally, ovarian cancer tissues were collected as the experimental group, and adjacent normal tissues were collected as the control group. The expression of claudin 4 (CLDN4) mRNA and protein levels were detected using real-time quantitative PCR (RT-qPCR) and Western-blot, and the results were compared between the two groups. Results CLDN4 was identified as a key gene in the development of OV. As its expression increased, the prognosis risk of OV patients worsened, which unfavorably impacted their overall survival (OS). A significant positive correlation was found between CLDN4 and dendritic cell (DC) in the OV microenvironment, and high expression of DCs was significantly associated with better OS in OV patients. The mRNA and protein expression levels of CLDN4 were significantly increased in OV tissues, with statistically significant differences. Conclusion CLDN4 is a key gene in the development of OV, and may serve as a potential biomarker and immunotherapy target for OV.
目的 筛选卵巢癌（OV）发生发展过程中的关键基因，分析免疫细胞浸润情况并构建风险模型，为OV患者的早期诊断、治疗及预后评估提供依据。方法 使用GEO2R数据分析工具对GSE18520和GSE6008数据集进行差异表达基因（DEG）分析，并绘制韦恩图。然后，对DEG进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析、蛋白质-蛋白质相互作用（PPI）网络以及突变、表达和预后分析以鉴定关键基因。接下来，构建风险模型并对关键基因进行免疫细胞浸润分析。最后，收集卵巢癌组织作为实验组，收集相邻正常组织作为对照组。采用实时定量PCR（RT-qPCR）和蛋白质免疫印迹法检测紧密连接蛋白4（CLDN4）mRNA和蛋白水平，并比较两组结果。结果 CLDN4被鉴定为OV发生发展中的关键基因。随着其表达增加，OV患者的预后风险恶化，对其总生存期（OS）产生不利影响。在OV微环境中，CLDN4与树突状细胞（DC）之间存在显著正相关，DC的高表达与OV患者较好的OS显著相关。CLDN4的mRNA和蛋白表达水平在OV组织中显著升高，差异具有统计学意义。结论 CLDN4是OV发生发展中的关键基因，可能作为OV潜在的生物标志物和免疫治疗靶点。
