Chen Jie, Ye Ziqi, Liu Lulu, Xuan Bixia
Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Transl Androl Urol. 2022 Apr;11(4):509-518. doi: 10.21037/tau-22-161.
Clear cell renal cell carcinoma (ccRCC) is one of the most common urological malignancies, and once metastasis occurs, it often has a poor prognosis and lacks effective treatment. Therefore, there is an urgent need to screen some new biomarkers and explore their molecular mechanisms to improve the early clinical diagnosis and targeted therapy of ccRCC. (SPARC/osteonectin, CWCV and Kazal-like domains proteoglycan 1) is a conserved multi-domain proteoglycan that plays an important role in the development of multiple cancer types; however, its prognostic value in ccRCC has not been investigated. The study of the prognostic value of in ccRCC is a good complement to the study of ccRCC biomarkers.
Databases of this study included Oncomine, Kaplan-Meier Plotter, GEPIA, GeneMANIA, cBioPortal, and TIMER. Student's -test was used to analyze the differences in expression in ccRCC tissues compared with tumor-adjacent normal tissues. Kaplan-Meier curves for survival analysis were used to assess the correlation between the expression of and the prognostic outcomes. Correlation module drew the expression scatterplots between and immune cell infiltration in ccRCC, together with the Spearman's rho value and estimated statistical significance.
The mRNA expression was significantly higher in ccRCC tissues (mean expression ± SD: 920.2±195.2) than in normal tissues (mean expression ± SD: 358.4±29.1, P=0.008), and high expression significantly and positively correlated with the pathological stage of ccRCC patients (F value =10.2, P<0.001). Higher expression of was also associated with significantly shorter overall survival (OS) and disease-free survival (DFS) in ccRCC patients (GEPIA: P=0.046, P<0.001, respectively; Kaplan-Meier Plotter: P=0.002, P=0.0022, respectively). The function of SPOCK1 is mainly related to tumor development and extracellular matrix remodeling, and it may participate in the epithelial-mesenchymal transition process. expression significantly and positively correlated with infiltration of several immune cells in ccRCC, including cancer-associated fibroblasts (CAFs) (Rho =0.333, P=2.16×10), tumor-associated macrophages (TAMs) (Rho =0.18, P=1.02×10), and tumor-associated neutrophils (TANs) (Rho =0.165, P=3.83×10). Conversely, there was a significant and negative correlation between expression and infiltration of CD4 T cells (Rho =-0.113, P=0.015).
may be a potential prognostic biomarker in ccRCC.
透明细胞肾细胞癌（ccRCC）是最常见的泌尿系统恶性肿瘤之一，一旦发生转移，其预后往往较差且缺乏有效的治疗方法。因此，迫切需要筛选一些新的生物标志物并探索其分子机制，以改善ccRCC的早期临床诊断和靶向治疗。富含半胱氨酸的酸性分泌蛋白（SPARC/骨连接蛋白，CWCV和Kazal样结构域蛋白聚糖1）是一种保守的多结构域蛋白聚糖，在多种癌症类型的发生发展中起重要作用；然而，其在ccRCC中的预后价值尚未得到研究。对其在ccRCC中预后价值的研究是对ccRCC生物标志物研究的良好补充。
本研究使用的数据库包括Oncomine、Kaplan-Meier Plotter、GEPIA、GeneMANIA、cBioPortal和TIMER。采用学生t检验分析ccRCC组织与癌旁正常组织中该蛋白表达的差异。生存分析的Kaplan-Meier曲线用于评估该蛋白表达与预后结果之间的相关性。相关性模块绘制了ccRCC中该蛋白表达与免疫细胞浸润之间的表达散点图，以及Spearman相关系数和估计的统计学意义。
ccRCC组织中该蛋白的mRNA表达（平均表达±标准差：920.2±195.2）显著高于正常组织（平均表达±标准差：358.4±29.1，P = 0.008），且该蛋白高表达与ccRCC患者的病理分期显著正相关（F值 = 10.2，P < 0.001）。该蛋白表达升高还与ccRCC患者的总生存期（OS）和无病生存期（DFS）显著缩短相关（GEPIA：分别为P = 0.046，P < 0.001；Kaplan-Meier Plotter：分别为P = 0.002，P = 0.0022）。富含半胱氨酸的酸性分泌蛋白1（SPOCK1）的功能主要与肿瘤发展和细胞外基质重塑有关，它可能参与上皮-间质转化过程。该蛋白表达与ccRCC中几种免疫细胞的浸润显著正相关，包括癌症相关成纤维细胞（CAFs）（相关系数 = 0.333，P = 2.16×10）、肿瘤相关巨噬细胞（TAMs）（相关系数 = 0.18，P = 1.02×10）和肿瘤相关中性粒细胞（TANs）（相关系数 = 0.165，P = 3.83×10）。相反，该蛋白表达与CD4 T细胞浸润之间存在显著负相关（相关系数 = -0.113，P = 0.015）。
该蛋白可能是ccRCC潜在的预后生物标志物。
