Department of Urology, Qingdao Municipal Hospital, Qingdao University, 266071, Qingdao, Shandong, China.
Department of Anesthesiology and Surgery, Qingdao Municipal Hospital, Qingdao University, 266071, Qingdao, Shandong, China.
Hereditas. 2022 May 11;159(1):20. doi: 10.1186/s41065-022-00234-z.
Spindle and kinetochore‑associated complex subunit 3 (SKA3) has recently been considered a key regulator of carcinogenesis. However, the connection between SKA3 and immune cell infiltration remains unknown.
The current study investigated the expression mode, prognostic effect, and functional role of SKA3 in different tumors, particularly bladder cancer using numerous databases, comprising TIMER, GEPIA, HPA, UALCAN, PrognoScan, and Kaplan-Meier Plotter. Differentially expressed gene and enrichment analyses were implemented on SKA3 using R packages "edgR" and "clusterProfiler". Immunohistochemistry was further used to validate the expression of SKA3 gene in bladder cancer. Following that, the relevance of SKA3 expression to immune infiltration level in bladder cancer was evaluated using TIMER.
Overall, the level of SKA3 expression in tumor tissue significantly increased than in normal tissue. In bladder cancer and other tumors, patients with high SKA3 expression levels had worse overall survival (OS) (p = 0.016), disease-specific survival (DSS) (p = 0.00004), and disease-free survival (DFS) (p = 0.032). Additionally, the major molecular functions for SKA3 included nuclear division, mitotic nuclear division, mitotic sister chromatid segregation, humoral immune response, and cell chemotaxis. Additionally, SKA3 expression was found to be positively associated with enhanced M2 macrophage and T helper (Th) 2 cell infiltration in bladder cancer.
Our study implies that SKA3 contributes to M2 macrophage and Th2 cell polarization by acting as an oncogene in bladder cancer. SKA3 might be a novel biomarker for evaluating prognosis and immune infiltration in bladder cancer.
纺锤体和着丝粒相关复合物亚基 3（SKA3）最近被认为是癌发生的关键调节因子。然而，SKA3 与免疫细胞浸润的联系尚不清楚。
本研究使用包括 TIMER、GEPIA、HPA、UALCAN、PrognoScan 和 Kaplan-Meier Plotter 在内的多个数据库，研究了 SKA3 在不同肿瘤中的表达模式、预后影响和功能作用，特别是膀胱癌。使用 R 包“edgR”和“clusterProfiler”对 SKA3 进行差异表达基因和富集分析。进一步使用免疫组织化学法验证 SKA3 基因在膀胱癌中的表达。随后，使用 TIMER 评估 SKA3 表达与膀胱癌免疫浸润水平的相关性。
总的来说，肿瘤组织中 SKA3 的表达水平明显高于正常组织。在膀胱癌和其他肿瘤中，高 SKA3 表达水平的患者总体生存率（OS）（p=0.016）、疾病特异性生存率（DSS）（p=0.00004）和无病生存率（DFS）（p=0.032）更差。此外，SKA3 的主要分子功能包括核分裂、有丝分裂核分裂、有丝分裂姐妹染色单体分离、体液免疫反应和细胞趋化性。此外，发现 SKA3 表达与膀胱癌中 M2 巨噬细胞和辅助性 T（Th）2 细胞浸润的增强呈正相关。
我们的研究表明，SKA3 通过作为膀胱癌中的癌基因，促进 M2 巨噬细胞和 Th2 细胞极化。SKA3 可能是评估膀胱癌预后和免疫浸润的新的生物标志物。
