Qin Shuhang, Yi Li, Liang Yanchun, Chen Yili, Wang Wei, Liao Yuandong, Zhang Chunyu, Huang Hua, Huang Jiaming, Yao Shuzhong
Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Genet. 2022 May 20;13:836509. doi: 10.3389/fgene.2022.836509. eCollection 2022.
Cervical cancer (CC) is the most common gynecological malignancy. Recently, an increasing number of studies have indicated that osteopontin (OPN) is a promising diagnostic and prognostic biomarker for CC. However, the biological role and detailed mechanism of OPN in CC remain unclear. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and a clinical sample microarray were used in our study. To identify the clinicopathological characteristics of OPN in CC, we compared the expression of OPN between normal and CC tissue samples and analyzed the correlations between OPN expression and multiple clinicopathological features. To identify biological processes involving OPN, OPN-associated genes were screened with Pearson correlation analysis and applied in hallmark gene set enrichment analysis (GSEA). Additionally, leukocyte infiltration was evaluated based on OPN expression. Finally, OPN-related signaling pathways were identified by GSEA. OPN expression was higher in CC samples than in normal tissue samples and positively correlated with age, FIGO stage, tumor size, lymphovascular invasion and an unfavorable prognosis. OPN-associated genes were mainly enriched in the immune response, and increased OPN expression was accompanied by increased M2 macrophage infiltration. Additionally, OPN was correlated with hypoxia, high glycolytic metabolism, apoptosis, angiogenesis, epithelial-mesenchymal transition and multiple signaling pathways (the p53 pathway, the PI3K/Akt pathway, IL6/STAT3 signaling, mTORC1 signaling and KRAS signaling). Our study showed that OPN is involved in immunological activities and multiple tumor processes, identifying it as a potential therapeutic target and useful prognostic factor in CC patients.
宫颈癌(CC)是最常见的妇科恶性肿瘤。最近,越来越多的研究表明,骨桥蛋白(OPN)是一种很有前景的CC诊断和预后生物标志物。然而,OPN在CC中的生物学作用和详细机制仍不清楚。我们的研究使用了癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)数据集以及临床样本微阵列。为了确定CC中OPN的临床病理特征,我们比较了正常组织样本和CC组织样本中OPN的表达,并分析了OPN表达与多种临床病理特征之间的相关性。为了确定涉及OPN的生物学过程,通过Pearson相关分析筛选出与OPN相关的基因,并将其应用于标志性基因集富集分析(GSEA)。此外,基于OPN表达评估白细胞浸润情况。最后,通过GSEA确定与OPN相关的信号通路。CC样本中OPN的表达高于正常组织样本,且与年龄、国际妇产科联盟(FIGO)分期、肿瘤大小、淋巴管浸润及不良预后呈正相关。与OPN相关的基因主要富集于免疫反应,OPN表达增加伴随着M2巨噬细胞浸润增加。此外,OPN与缺氧、高糖酵解代谢、细胞凋亡、血管生成、上皮-间质转化以及多种信号通路(p53通路、PI3K/Akt通路、IL6/STAT3信号传导、mTORC1信号传导和KRAS信号传导)相关。我们的研究表明,OPN参与免疫活动和多个肿瘤过程,确定其为CC患者潜在的治疗靶点和有用的预后因素。