Abstract：
BACKGROUND: BLCA is a common urothelial malignancy characterized by a high recurrence rate. Despite its prevalence, the molecular mechanisms underlying its development remain unclear.
OBJECTIVE: This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA).
OBJECTIVE: The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease.
METHODS: We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays.
RESULTS: In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels.
CONCLUSIONS: In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.
OBJECTIVE: This study aimed to explore new prognostic biomarkers and investigate the underlying mechanism of bladder cancer (BLCA).
OBJECTIVE: The objective of this study is to identify key prognostic biomarkers for BLCA and to elucidate their roles in the disease.
METHODS: We first collected the overlapping DEGs from GSE42089 and TCGA-BLCA samples for the subsequent weighted gene co-expression network analysis (WGCNA) to find a key module. Then, key module genes were analyzed by the MCODE algorithm, prognostic risk model, expression and immunohistochemical staining to identify the prognostic hub gene. Finally, the hub gene was subjected to clinical feature analysis, as well as cellular function assays.
RESULTS: In WGCNA on 1037 overlapping genes, the blue module was the key module. After a series of bioinformatics analyses, POLE2 was identified as a prognostic hub gene in BLCA from potential genes (TROAP, POLE2, ANLN, and E2F8). POLE2 level was increased in BLCA and related to different clinical features of BLCA patients. Cellular assays showed that si-POLE2 inhibited BLCA proliferation, and si-POLE2+ 740Y-P in BLCA cells up-regulated the PI3K and AKT protein levels.
CONCLUSIONS: In conclusion, POLE2 was identified to be a promising prognostic biomarker as an oncogene in BLCA. It was also found that POLE2 exerts a promoting function by the PI3K/AKT signaling pathway in BLCA.
摘要：
背景：BLCA是一种常见的尿路上皮恶性肿瘤，其特点是复发率高。尽管流行,其发展的分子机制尚不清楚.
目的：本研究旨在探索新的预后生物标志物，并探讨膀胱癌（BLCA）的潜在机制。
目的：本研究的目的是确定BLCA的关键预后生物标志物并阐明其在疾病中的作用。
方法：我们首先从GSE42089和TCGA-BLCA样品中收集重叠的DEGs，用于随后的加权基因共表达网络分析（WGCNA），以找到关键模块。然后，通过MCODE算法对关键模块基因进行了分析，预后风险模型，表达和免疫组织化学染色以鉴定预后hub基因。最后,hub基因进行临床特征分析，以及细胞功能测定。
结果：在1037个重叠基因的WGCNA中，蓝色模块是关键模块。经过一系列的生物信息学分析,POLE2被鉴定为BLCA中潜在基因的预后中心基因(TROAP，POLE2ANLN,和E2F8）。POLE2水平在BLCA中升高，与BLCA患者的不同临床特征有关。细胞实验表明si-POLE2抑制BLCA增殖,BLCA细胞中的si-POLE2+740Y-P上调PI3K和AKT蛋白水平。
结论：结论：POLE2作为BLCA的癌基因被鉴定为有希望的预后生物标志物。还发现POLE2在BLCA中通过PI3K/AKT信号通路发挥促进功能。
目的：本研究旨在探索新的预后生物标志物，并探讨膀胱癌（BLCA）的潜在机制。
目的：本研究的目的是确定BLCA的关键预后生物标志物并阐明其在疾病中的作用。
方法：我们首先从GSE42089和TCGA-BLCA样品中收集重叠的DEGs，用于随后的加权基因共表达网络分析（WGCNA），以找到关键模块。然后，通过MCODE算法对关键模块基因进行了分析，预后风险模型，表达和免疫组织化学染色以鉴定预后hub基因。最后,hub基因进行临床特征分析，以及细胞功能测定。
结果：在1037个重叠基因的WGCNA中，蓝色模块是关键模块。经过一系列的生物信息学分析,POLE2被鉴定为BLCA中潜在基因的预后中心基因(TROAP，POLE2ANLN,和E2F8）。POLE2水平在BLCA中升高，与BLCA患者的不同临床特征有关。细胞实验表明si-POLE2抑制BLCA增殖,BLCA细胞中的si-POLE2+740Y-P上调PI3K和AKT蛋白水平。
结论：结论：POLE2作为BLCA的癌基因被鉴定为有希望的预后生物标志物。还发现POLE2在BLCA中通过PI3K/AKT信号通路发挥促进功能。
