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SKA1 overexpression is associated with poor prognosis in hepatocellular carcinoma.

ABSTRACT: BACKGROUND:SKA1, an important mitosis protein, has been indicated in the initiation and progression of several malignancies. However, its clinical significance in hepatocellular carcinoma (HCC) remain to be elucidated. METHODS:mRNA expression of SKA1 was examined in 126 HCC and paired non-neoplastic tissues using real-time PCR and validated in The Cancer Genome Atlas (TCGA) database. SKA1 protein expression was detected using immunohistochemistry in the 126 HCC tissues and its associations with clinicopathological parameters and prognosis were analyzed. Hierarchical cluster analysis and gene set enrichment analysis (GSEA) were performed in selected Gene Expression Omnibus data sets. RESULTS:SKA1 mRNA expression was significantly elevated in HCC tissues from both local hospital and TCGA database. Immunohistochemistry revealed that increased SKA1 expression was present in 65 of the 126 cases and was significantly associated with higher serum alpha-fetoprotein concentration, larger tumor size and higher TNM stage. Patients with positive SKA1 expression showed significantly worse overall and relapse-free survival. Multivariate Cox regression analysis revealed that SKA1 was an independent predictor of patient prognosis. Gene expression profiling analysis of public data showed that high-SKA1 expression HCC tissues had similar gene expression profiles with fetal liver tissues. Moreover, GSEA showed that genes up-regulated in high SKA1 HCC subgroup were significantly enriched in cell cycle pathway, while genes down-regulated were significantly enriched in apoptosis pathway. CONCLUSIONS:Our findings indicate that the oncofetal gene SKA1 might be involved in the progression of the HCC and could serve as a prognostic marker for HCC.

SUBMITTER: Chen Y

PROVIDER: S-EPMC6288885 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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SKA1 overexpression is associated with poor prognosis in hepatocellular carcinoma.

Chen Yibing Y Zhao Jingjing J Jiao Zhihui Z Wang Weiwei W Wang Dandan D Yu Xiaohe X Shi Zhiyong Z Ge Naijian N Pan Qiuzhong Q Xia Jianchuan J Niu Wancheng W Zhao Ruihua R Zhang Xiaofei X Du Wei W

BMC cancer 20181211 1

<h4>Background</h4>SKA1, an important mitosis protein, has been indicated in the initiation and progression of several malignancies. However, its clinical significance in hepatocellular carcinoma (HCC) remain to be elucidated.<h4>Methods</h4>mRNA expression of SKA1 was examined in 126 HCC and paired non-neoplastic tissues using real-time PCR and validated in The Cancer Genome Atlas (TCGA) database. SKA1 protein expression was detected using immunohistochemistry in the 126 HCC tissues and its ass ...[more]

PMID: 30537941

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Project description:Purpose:Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed digestive cancers and the fourth leading cause of death worldwide. Long noncoding RNAs (lncRNAs) with key roles in HCC development and progression have emerged and are used in the diagnosis and prognostic prediction of HCC. The lncRNA gradually increased during hepatocarcinogenesis (GIHCG) is a novel lncRNA with aberrant expression in many tumors, but its prognostic value and biological role in HCC have not been fully studied. Thus, the aim of this study was to explore the expression pattern and potential biological role of GIHCG in HCC. Patients and Methods:The expression pattern of GIHCG in HCC was analyzed in our HCC cohort and validated in The Cancer Genome Atlas (TCGA) database. To assess the prognostic value of GIHCG, survival analyses and Cox regression analyses were carried out in two HCC cohorts. Functional enrichment analysis was used to predict the gene sets and pathways related to aberrant GIHCG expression. Furthermore, the relationship between GIHCG expression and immune infiltration in HCC was analyzed. Results:GIHCG was highly expressed in HCC tissues compared with normal liver tissues. In addition, high GIHCG expression was significantly correlated with inferior clinicopathological characteristics and shorter survival times. High GIHCG expression was an independent prognostic factor for overall survival and disease-free survival in the HCC cohort in our center and in the TCGA-LIHC cohort. Hallmark terms such as "G2M checkpoint", "MYC targets" and "DNA repair" were enriched in the GIHCG high-expression groups. High GIHCG expression negatively correlated with the infiltration of memory CD4+ and CD8+ T cells, natural killer cells, macrophages, dendritic cells, neutrophils and monocytes. Conclusion:The findings of our study indicate that GIHCG is a biomarker that can be used to predict the prognosis of HCC patients and is correlated with immune cell infiltration in HCC.

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SKA1 overexpression is associated with poor prognosis in hepatocellular carcinoma.

Publications

SKA1 overexpression is associated with poor prognosis in hepatocellular carcinoma.

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