Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, 730000, China.
Department of Orthopedics, Xigu Branch of the Second Hospital of Lanzhou University, Lanzhou, 730000, China.
Sci Rep. 2021 May 27;11(1):11165. doi: 10.1038/s41598-021-89628-z.
The spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.
纺锤体和着丝粒相关蛋白复合物（Ska）是染色体分离的必需组成部分。它由三种蛋白质（Ska1、Ska2 和 Ska3）组成，其理论作用是导致染色体不稳定和肿瘤发展，并且其过表达已在多种肿瘤中广泛报道。然而，Ska 蛋白在肝细胞癌（HCC）中的预后意义和免疫浸润尚不完全清楚。使用 Oncomine、UALCAN、基因表达谱交互分析 2（GEPIA2）、cBioPortal、GeneMANIA、Metascape 和 TIMER 等生物信息学工具分析了 HCC 患者中 Ska 蛋白复合物的差异表达、预后价值、遗传改变和免疫细胞浸润。我们发现 Ska 复合物的 mRNA 表达在 HCC 中明显上调。Ska 复合物的高表达与肿瘤分期、患者种族、肿瘤分级和 TP53 突变状态密切相关。此外，Ska 复合物的高表达与无病生存时间显著相关，而 Ska1 和 Ska3 的高表达水平与总生存时间较短相关。Ska 复合物在 HCC 中的生物学功能主要涉及从着丝粒、有丝分裂纺锤体和（通过 MAD2 入侵信号）未连接的着丝粒放大信号。此外，复合物的表达与肿瘤浸润细胞呈正相关。这些结果可能为 HCC 的免疫治疗靶点和预后生物标志物的开发提供新的见解。
