Abstract
BackgroundMalignant tumors were considered as the leading causes of cancer-related mortality globally. More and more studies found that dysregulated genes played an important role in carcinogenesis. The aim of this study was to explore the significance of KPNA2 in human six major cancers including non-small cell lung cancer (NSCLC), gastric cancer, colorectal cancer, breast cancer, hepatocellular carcinoma, and bladder cancer based on bioinformatics analysis.MethodsThe data were collected and comprehensively analyzed based on multiple databases. KPNA2 mRNA expression in six major cancers was investigated in Oncomine, the human protein atlas, and GEPIA databases. The mutation status of KPNA2 in the six major cancers was evaluated by online data analysis tool Catalog of Somatic Mutations in Cancer (COSMIC) and cBioPortal. Co-expressed genes with KPNA2 were identified by using LinkedOmics and made pairwise correlation by Cancer Regulome tools. Protein-protein interaction (PPI) network relevant to KPNA2 was constructed by STRING database and KEGG pathway of the included proteins of the PPI network was explored and demonstrated by circus plot. Survival analysis-relevant KPNA2 of the six cancers was performed by GEPIA online data analysis tool based on TCGA database.ResultsCompared with paired normal tissue, KPNA2 mRNA was upregulated in all of the six types of cancers. KPNA2 mutations, especially missense substitution, were widely identified in six cancers and interact with different genes in different cancer types. Genes involved in PPI network were mainly enriched in p53 signaling pathway, cell cycle, viral carcinogenesis, and Foxo signaling pathway. KPNA2 protein was mainly expressed in nucleoplasm and cytosol in cancer cells. Immunohistochemistry assay indicated that KPNA2 protein was also positively expressed in nucleoplasm with brownish yellow staining. Overall survival (OS) and progression free survival (PFS) were different between KPNA2 high and low expression groups.ConclusionsKPNA2 was widely dysregulated and mutated in carcinomas and correlated with the patients prognosis which may be potential target for cancer treatment and biomarker for prognosis.
Highlights
Cancer is the leading cause of death globally
Karyopherin subunit alpha 2 (KPNA2) protein expression in tumor cell lines and cancer tissues was detected by immunofluorescent staining and immunohistochemistry assay in the human protein atlas database
KPNA2 mRNA expression levels in different type cancers are showed in Figure 1b, which indicated that the expression level across different cancers was not obviously different
Summary
Cancer is the leading cause of death globally. According to the cancer statistical analysis in year 2018, 9.6 million deaths and 18.1 million new cases of all types of cancers were estimated [1]. Lung cancer especially non-small cell lung cancer (NSCLC), gastric cancer, colorectal cancer, breast cancer, liver hepatic cancer, and bladder cancer were the most common carcinomas diagnosed clinically with high incidence and mortality [2,3]. The above six cancers had high incidence and poor prognosis, the general carcinogenesis was not completely cleart. With the development of biology and life science, more and more evidence had made it clear that the driving genes had played an important role in the carcinogenesis and pathways [4]. The driving genes including oncogenes and tumor suppressor genes involved in the cell division, apoptosis [5], proliferation [6], and migration may act as the general phenotype of malignant carcinoma
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