首页|Spindle and Kinetochore-associated Family Genes are Prognostic and Predictive Biomarkers in Hepatocellular Carcinoma

Spindle and Kinetochore-associated Family Genes are Prognostic and Predictive Biomarkers in Hepatocellular Carcinoma

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Background and Aims: Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors. Spindle and kinetochore-associated (SKA) family genes are essential for the maintenance of the metaphase plate and spindle checkpoint silencing during mitosis. Recent studies have indicated that dysregulation of SKA family genes induces tumorigenesis, tumor progression, and chemoresistance via modulation of cell cycle and DNA replication. However, the differential transcription of SKAs in the context of HCC and its prognostic significance has not been demonstrated. Methods: Bioinformatics analyses were performed using TCGA, ONCOMINE, HCCDB, Kaplan-Meier plotter, STRING, GEPIA databases. qRT-PCR, western blot, and functional as-says were utilized for in vitro experiments. Results: We found remarkable upregulation of transcripts of SKA family genes in HCC samples compared with normal liver samples on bioinformatics analyses and in vitro validation. Inter-action analysis and enrichment analysis showed that SKA family members were mainly related to microtubule motor activity, mitosis, and cell cycle. Immuno-infiltration analysis showed a correlation of all SKA family genes with various immune cell subsets, especially T helper 2 (Th2) cells. Tran-scriptional levels of SKA family members were positively as-sociated with histologic grade, T stage, and α-fetoprotein in HCC patients. Receiver operating characteristic curve analy-sis demonstrated a strong predictive ability of SKA1/2/3 for HCC. Increased expression of these SKAs was associated with unfavorable overall survival, progression-free survival, and disease-specific survival. On Cox proportional hazards regression analyses, SKA1 upregulation and pathological staging were independent predictors of overall survival and disease-specific survival of HCC patients. Finally, clinical tissue microarray validation and in vitro functional assays revealed SKA1 acts an important regulatory role in tumor malignant behavior. Conclusions: SKA family members may potentially serve as diagnostic and prognostic markers in the context of HCC. The correlation between SKAs and immune cell infiltration provides a promising research direc-tion for SKA-targeted immunotherapeutics for HCC.

Spindle and kinetochore-associated genesLiver hepatocellular carcinomaPrognostic valueImmune infiltrationBioinformatics analysis.

Chenhui Cai、Ying Zhang、Xu Hu、Sizhen Yang、Jiawen Ye、Zihan Wei、Tongwei Chu

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Department of Orthopedics,Xinqiao Hospital,Third Military Medical University(Army Medical University),Chongqing,China

General project of Chong-qing Natural Science Foundation of ChinaNational Key Research and Development Plan ProjectClinical Research Project of the Second Affiliated Hospital of the Army Military Medical University

cstc2020j-cyj-msxmX06882016YFC11015042018XLC2016

2022

10.14218/JCTH.2021.00216

临床与转化肝病杂志(英文版)

临床与转化肝病杂志(英文版)

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年,卷(期)：2022.10(4)
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