泛癌中FGFR3表达的预后意义及其免疫调节作用

Prognostic significance and immunomodulatory effect of FGFR3 expression in pan-carcinoma

目的通过生物信息学方法研究FGFR3基因在人肿瘤组织内基因及蛋白表达,探究其对肿瘤临床预后评估价值。方法利用TIMER2和GEPIA2数据库分析FGFR3基因在肿瘤组织中的表达情况和预后情况;利用cBioPortal数据库和R包分析FGFR3基因变异数据;利用TIME2分析FGFR3表达与肿瘤细胞免疫浸润之间的关系;使用STRING,GEPIA2,Veen网站和R包进行FGFR3相关基因富集分析。结果FGFR3在绝大多数肿瘤中高表达,与膀胱尿路上皮癌、肺腺癌等肿瘤的临床分期呈正相关。FGFR3最主要的变异类型是错义突变,在膀胱尿路上皮癌中的突变频率最高,FGFR3突变与膀胱尿路上皮癌患者预后差有关,FGFR3扩增与肾上腺皮质癌、子宫癌肉瘤患者预后差有关。在结肠癌、睾丸癌等肿瘤中FGFR3表达与癌相关成纤维细胞的浸润呈负相关。FGFR3可能通过“MAPK信号通路”和“PI3K-Akt信号通路”参与肿瘤的发生发展。结论FGFR3表达与临床预后、基因突变、肿瘤细胞免疫浸润间存在相关性。FGFR3可能成为肺腺癌、子宫癌肉瘤、结肠癌、肝癌等肿瘤的新的预后标志物及诊疗的潜在靶点,并在一定程度上调节多种肿瘤的免疫反应。

【Objective】To study the gene and protein expression of FGFR3 in human tumor tissue by bioinformatics method,and to explore its value in evaluating the clinical prognosis of tumor.【Methods】The expression and prognosis of FGFR3 gene in tumor tissues were analyzed by TIMER2 and GEPIA2 database;The FGFR3 gene variation data were analyzed by cBioPortal database and R packet;The relationship between FGFR3 expression and immune infiltration of tumor cells was analyzed by TIME2;STRING,GEPIA2,Veen website and R package were used to analyze the enrichment of FGFR3 related genes.【Results】FGFR3 was highly expressed in most tumors,and was positively correlated with clinical stages of bladder urothelial carcinoma and lung adenocarcinoma.The main mutation type of FGFR3 was missense mutation,and the mutation frequency was the highest in bladder urothelial carcinoma.FGFR3 mutation was related to poor prognosis of patients with bladder urothelial carcinoma.FGFR3 amplification was related to poor prognosis of patients with adrenal cortical carcinoma and uterine carcinosarcoma.The expression of FGFR3 was negatively correlated with the infiltration of cancer-related fibroblasts in colon cancer and testicular cancer.FGFR3 may be involved in the occurrence and development of tumors through"MAPK signaling pathway"and"PI3K-Akt signaling pathway".【Conclusion】The expression of FGFR3 is correlated with clinical prognosis,gene mutation and immune infiltration of tumor cells.FGFR3 may be a new prognostic marker and potential target for diagnosis and treatment of lung adenocarcinoma,uterine carcinosarcoma,colon cancer,hepatocellular carcinoma,and other tumors,and regulate the immune response of many kinds of tumors to some extent.