背景:锌指蛋白337(ZNF337)是一种新型的锌指(ZNF)蛋白家族成员。然而,ZNF337在人类癌症中的作用尚未被研究.
方法:在本研究中,借助TCGA数据库,GTEx数据库,和在线网站,我们测定了ZNF337在泛癌症中的表达水平及其作为泛癌症诊断和预后标志物的潜在价值,并分析了ZNF337表达与免疫细胞浸润和免疫检查点基因之间的关系.然后,我们将研究重点放在ZNF337作为KIRC(肾透明细胞癌)诊断和预后的生物标志物的潜力上,并在E-MTAB-1980数据库中进行了验证。此外,通过qRT-PCR和Westernblotting(WB)检测ZNF337的表达。CCK-8实验,菌落形成实验,进行EDU实验以评估细胞增殖能力。采用创面愈合试验和transwell试验分析其迁移能力。采用qRT-PCR和WB检测KIRC患者肿瘤组织和癌旁组织中ZNF337的表达。
结果:泛癌症分析显示,在多种人类癌症类型中发现了异常的ZNF337表达。ZNF337在泛癌症中具有很高的诊断价值,并且与某些癌症的预后显着相关。表明ZNF337可能是多种癌症的有价值的预后生物标志物。进一步的分析表明,ZNF337的表达水平与癌症相关的成纤维细胞显着相关。免疫细胞浸润,和许多肿瘤中的免疫检查点基因。此外,观察到ZNF337在KIRC中具有高表达。其表达与不良预后[总生存期(OS),疾病特异性生存率(DSS)],年龄,TNM阶段,组织学分级,病理阶段。在E-MTAB-1980验证队列中,高ZNF337表达与不良预后相关。体外实验提示ZNF337在KIRC肿瘤组织中的表达高于癌旁组织,ZNF337敲低抑制KIRC细胞增殖和迁移,而ZNF337的过表达具有相反的作用。
结论:ZNF337可能是泛癌症的重要预后和免疫治疗生物标志物,尤其是在KIRC。
BACKGROUND: Zinc Finger Protein 337 (ZNF337) is a novel Zinc Finger (ZNF) protein family member. However, the roles of ZNF337 in human cancers have not yet been investigated.
METHODS: In this study, with the aid of TCGA databases, GTEx databases, and online websites, we determined the expression levels of ZNF337 in pan-cancer and its potential value as a diagnostic and prognostic marker for pan-cancer and analyzed the relationship between ZNF337 expression and immune cell infiltration and immune checkpoint genes. We then focused our research on the potential of ZNF337 as a biomarker for diagnostic and prognostic in KIRC (kidney renal clear cell carcinoma) and validated in the E-MTAB-1980 database. Moreover, the expression of ZNF337 was detected through qRT-PCR and Western blotting (WB). CCK-8 experiment, colony formation experiment, and EDU experiment were performed to evaluate cell proliferation ability. Wound healing assay and transwell assay were used to analyze its migration ability. The qRT-PCR and WB were used to detect the expression of ZNF337 in tumor tissues and paracancerous tissues of KIRC patients.
RESULTS: The pan-cancer analysis revealed that abnormal ZNF337 expression was found in multiple human cancer types. ZNF337 had a high diagnostic value in pan-cancer and a significant association with the prognosis of certain cancers, indicating that ZNF337 may be a valuable prognostic biomarker for multiple cancers. Further analysis demonstrated that the expression level of ZNF337 displayed significant correlations with cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes in many tumors. Additionally, ZNF337 was observed to have a high expression in KIRC. Its expression was significantly associated with poor prognosis [overall survival (OS), disease-specific survival (DSS)], age, TNM stage, histologic grade, and pathologic stage. The high ZNF337 expression was associated with poor prognosis in the E-MTAB-1980 validation cohort. The in vitro experiments suggested that the expression of ZNF337 in KIRC tumor tissues was higher than in adjacent tissues, and ZNF337 knockdown inhibited the proliferation and migration of KIRC cells, whereas overexpression of ZNF337 had the opposite effects.
CONCLUSIONS: ZNF337 might be an important prognostic and immunotherapeutic biomarker for pan-cancer, especially in KIRC.