Zhong Quliang, Jiang Kehua, Zhang Facai, Tian Yuan, Gu Jiang, Li Tao, Chen Xulong, Yang Jianjun, Sun Fa
Guizhou Medical University Guiyang 550001, Guizhou, China.
Department of Urology, Affiliated Hospital of Guizhou Medical University Guiyang 550001, Guizhou, China.
Am J Cancer Res. 2023 Jun 15;13(6):2213-2233. eCollection 2023.
Bladder cancer (BLCA) is a common malignant neoplasm of the urinary system. Glycolysis is an essential metabolic pathway regulated by various genes with implications for tumor progression and immune escape. Scoring the glycolysis for each sample in the TCGA-BLCA dataset was done using the ssGSEA algorithm for quantification. The results showed that the score in BLCA tissues was markedly greater than those in adjacent tissues. Additionally, the score was found to be correlated with metastasis and high pathological stage. Functional enrichment analyses of the glycolysis-related genes showed they were related to roles associated with tumor metastasis, glucose metabolism, cuproptosis, and tumor immunotherapy in BLCA. Using 3 different machine learning algorithms, we identified chondroitin polymerizing factor () as a central glycolytic gene with high expression in BLCA. In addition, we showed is a valuable diagnostic marker of BLCA with an area under the ROC (AUC) of 0.81. Sequencing BLCA 5637 cells after siRNA-mediated silencing and bioinformatics revealed that positively correlated with the markers of epithelial-to-mesenchymal transformation (EMT), glycometabolism-related enzymes, and immune cell infiltration. In addition, silencing inhibited the infiltration of multiple immune cells in BLCA. Genes that promote cuproptosis negatively correlated with expression and were up-regulated after silencing. High expression was a risk factor for overall and progression-free survival of patients who received immunotherapy for BLCA. Finally, using immunohistochemistry, we demonstrated that the CHPF protein had high expression in BLCA, increasing in high-grade tumors and those with muscle invasion. The CHPF expression levels were also positively associated with F-fluorodeoxyglucose uptake in PET/CT images. We conclude that the glycolysis-related gene is an effective diagnostic and treatment target for BLCA.
膀胱癌（BLCA）是泌尿系统常见的恶性肿瘤。糖酵解是一种由多种基因调控的重要代谢途径，与肿瘤进展和免疫逃逸相关。使用ssGSEA算法对TCGA - BLCA数据集中的每个样本进行糖酵解评分以进行量化。结果显示，BLCA组织中的评分明显高于相邻组织。此外，该评分与转移和高病理分期相关。对糖酵解相关基因的功能富集分析表明，它们与BLCA中与肿瘤转移、葡萄糖代谢、铜死亡和肿瘤免疫治疗相关的作用有关。使用3种不同的机器学习算法，我们确定硫酸软骨素聚合因子（CHPF）是BLCA中高表达的核心糖酵解基因。此外，我们表明CHPF是BLCA的一个有价值的诊断标志物，ROC曲线下面积（AUC）为0.81。对siRNA介导的CHPF沉默后的BLCA 5637细胞进行测序和生物信息学分析表明，CHPF与上皮 - 间质转化（EMT）标志物、糖代谢相关酶和免疫细胞浸润呈正相关。此外，CHPF沉默抑制了BLCA中多种免疫细胞的浸润。促进铜死亡的基因与CHPF表达呈负相关，在CHPF沉默后上调。CHPF高表达是接受BLCA免疫治疗患者总生存和无进展生存的危险因素。最后，通过免疫组织化学，我们证明CHPF蛋白在BLCA中高表达，在高级别肿瘤和有肌肉浸润的肿瘤中增加。CHPF表达水平也与PET/CT图像中F - 氟脱氧葡萄糖摄取呈正相关。我们得出结论，糖酵解相关基因CHPF是BLCA的有效诊断和治疗靶点。
