Wang Zhiping, Zhang Mengyan, Wu Yahua, Yu Yilin, Zheng Qunhao, Li Jiancheng
Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China.
J Cancer. 2021 Oct 11;12(23):6964-6978. doi: 10.7150/jca.63625. eCollection 2021.
Cyclin-dependent kinase regulatory subunit 2 (CKS2) plays a vital role in regulation of the cell cycle and cancer progression. However, the role of CKS2 in lung adenocarcinoma (LUAD) remains unkonwn. Here, we examined the prognostic value and biological functions of CKS2 in LUAD by using omics data of 1,235 LUAD samples from TCGA, GEO, and our own cohort as well as data of experiments. Kaplan-Meier was conducted to evaluate the prognostic value of CKS2 expression. The association between CKS2 expression level and tumor immune infiltration was explored using the single-sample Gene Set Enrichment Analysis (ssGSEA) and TIMER database. Functional enrichment analyses were performed to annotate the biological functions of CKS2 in LUAD. Furthermore, a series of experiments and immunohistochemistry were performed for validation. CKS2 overexpression was correlated with the advanced stage, TP53 status, PD-L1 expression, and DNA hypomethylation. Moreover, patients with LUAD and high CKS2 expression exhibited poor overall survival. Functional enrichment analysis indicated that CKS2 was involved in cell division, cell cycle, DNA replication. Experiments indicated that CKS2 knockdown decreased the invasion and proliferation of LUAD cells and facilitated their apoptosis. ssGSEA and TIMER analysis revealed a negative correlation between CKS2 expression and the immune cell infiltration In summary, High CKS2 expression was associated with poor prognosis and low levels of infiltrating immune cells in LUAD as well as with malignant phenotypes. Therefore, CKS2 may be a promising prognostic biomarker and therapeutic target in LUAD.
细胞周期蛋白依赖性激酶调节亚基2(CKS2)在细胞周期调控和癌症进展中起着至关重要的作用。然而,CKS2在肺腺癌(LUAD)中的作用仍不清楚。在此,我们通过使用来自TCGA、GEO以及我们自己队列的1235例LUAD样本的组学数据以及实验数据,研究了CKS2在LUAD中的预后价值和生物学功能。采用Kaplan-Meier法评估CKS2表达的预后价值。使用单样本基因集富集分析(ssGSEA)和TIMER数据库探讨CKS2表达水平与肿瘤免疫浸润之间的关联。进行功能富集分析以注释CKS2在LUAD中的生物学功能。此外,还进行了一系列实验和免疫组织化学以进行验证。CKS2过表达与晚期、TP53状态、PD-L1表达和DNA低甲基化相关。此外,LUAD且CKS2高表达的患者总生存期较差。功能富集分析表明CKS2参与细胞分裂、细胞周期和DNA复制。实验表明,敲低CKS2可降低LUAD细胞的侵袭和增殖并促进其凋亡。ssGSEA和TIMER分析显示CKS2表达与免疫细胞浸润呈负相关。总之,高CKS2表达与LUAD的不良预后、低浸润免疫细胞水平以及恶性表型相关。因此,CKS2可能是LUAD中一个有前景的预后生物标志物和治疗靶点。