More and more evidence suggests the oncogenic function of overexpressed CDC28 protein kinase regulatory subunit 2 (CKS2) in various human cancers. However, CKS2 has rarely been studied in cervical cancer. Herein, taking advantage of massive genetics data from multicenter RNA-seq and microarrays, we were the first group to perform tissue microarrays for CKS2 in cervical cancer. We were also the first to evaluate the clinical significance of CKS2 with large samples (980 cervical cancer cases and 422 noncancer cases). We further excavated the mechanism of the tumor-promoting activities of CKS2 in cervical cancer through analysis of genetic mutation profiles, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) significant enrichment of genes coexpressed with CKS2. According to the results, expression data from multilevels unanimously supported the overexpression of CKS2 in cervical cancer. Patients with cervical cancer in stage II from inhouse microarrays had significantly higher expression of CKS2, and CKS2 overexpression had an adverse impact on the disease-free survival status of cervical cancer patients in GSE44001. Both mutation types of mRNA high and mRNA low appeared in cervical cancer cases from the TCGA Firehose project. Gene coexpressed with CKS2 participated in pathways including the cell cycle, estrogen signaling pathway, and DNA replication. In summary, upregulated CKS2 is closely associated with the malignant clinical development of cervical cancer and might serve as a valuable therapeutic target in cervical cancer.

中文翻译：

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CDC28蛋白激酶调节亚基2在宫颈癌中的综合表达谱和分子基础

越来越多的证据表明过表达的 CDC28 蛋白激酶调节亚基 2 (CKS2) 在各种人类癌症中的致癌功能。然而，CKS2在宫颈癌中的研究很少。在这里，利用来自多中心 RNA-seq 和微阵列的大量遗传学数据，我们是第一个在宫颈癌中为 CKS2 进行组织微阵列的团队。我们也是第一个用大样本（980 例宫颈癌病例和 422 例非癌病例）评估CKS2的临床意义的人。我们进一步挖掘了CKS2的促肿瘤活性机制通过基因突变谱、基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 分析宫颈癌中与CKS2共表达的基因显着富集。结果显示，多层次的表达数据一致支持CKS2在宫颈癌中的过表达。来自内部微阵列的II期宫颈癌患者CKS2的表达明显更高，CKS2过表达对GSE44001中宫颈癌患者的无病生存状态有不利影响。来自 TCGA Firehose 项目的宫颈癌病例中出现了 mRNA 高和 mRNA 低的两种突变类型。与CKS2共表达的基因参与细胞周期、雌激素信号通路和DNA复制等途径。总之，上调的CKS2与宫颈癌的恶性临床发展密切相关，可能作为宫颈癌的有价值的治疗靶点。