Aberrant expression of KPNA2 is associated with a poor prognosis and contributes to OCT4 nuclear transportation in bladder cancer

Zhou, Jingcheng; Dong, Daoquan; Cheng, Ran; Wang, Yan; Jiang, Shuhan; Zhu, Yiping; Fan, Longlong; Mao, Xiangming; Gui, Yaoting; Li, Zesong; Li, Xianxin; Bing, Shi

doi:10.18632/oncotarget.11889

Cited by 27 publications

(27 citation statements)

References 30 publications

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“…Several studies have recently demonstrated that KPNA2 is up-regulated in multiple malignancies [23][24][25]. Its aberrant expression is often associated with adverse outcomes in affected patients, indicating that KPNA2 plays a signi cant role in carcinogenesis and tumor progression [23,26,27]. These ndings are supported by previous studies, which reported that KPNA2 may have a functional role in the malignant transformation of cells.…”

Section: Discussionsupporting

confidence: 70%

“…Given its function in nucleocytoplasmic transport, KPNA2 mediates the translocation of various proteins and is involved in numerous cellular processes, such as cellular differentiation, proliferation and apoptosis, transcriptional regulation, immune response, and viral infection. Several studies have recently demonstrated that KPNA2 is up-regulated in multiple malignancies [23][24][25]. Its aberrant expression is often associated with adverse outcomes in affected patients, indicating that KPNA2 plays a signi cant role in carcinogenesis and tumor progression [23,26,27].…”

Section: Discussionmentioning

confidence: 99%

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Integrative Bioinformatics Analysis of KPNA2 in Six Major Human Cancers

Liu

Xiu

2020

Preprint

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Background Malignant tumors were considered as the leading causes of mortality globally. More and more studies found that dysregulated genes played an important role in the carcinogenesis. The aim of this study was to explore the significance of KPNA2 in human five major cancers including non-small cell lung cancer (NSCLC), gastric cancer, colorectal cancer, breast cancer, hepatocellular carcinoma and bladder cancer based on bioinformatics analysis. Methods The data were collected and comprehensive analyzed based on multiple databases. KPNA2 mRNA expression in 6 major cancers were investigated in Oncomine, the human protein atlas and GEPIA databases. The mutation status of KPNA2 in the 6 major cancers were 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 6 cancers were performed by GEPIA online data analysis tool based on TCGA database. Results Compared with paired normal tissue, KPNA2 mRNA was up-regulated in all of the 6 type cancers. KPNA2 mutations especially missense substitution were widely identified in 6 major 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, Foxo signaling pathway and et c. KPNA2 protein was mainly localized to the nucleoplasm and cytosol in cancer cells. Immunohistochemistry assay indicated that KPNA2 protein was also positive expressed in nucleoplasm with brownish yellow staining. Overall survival (OS) and progression free survival (PFS) were generally different between KPNA2 high and low expression groups. Conclusions KPNA2 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.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Integrative Bioinformatics Analysis of KPNA2 in Six Major Human Cancers

Liu

Xiu

2020

Preprint

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“…KPNA2 is overexpressed in BCa and associated with poor prognosis [83]. Moreover, the expression levels of KPNA2 and OCT4 are significantly associated with primary tumor stage [84].…”

Section: The Hub Genes Potentially Associated With the Clinical Prognmentioning

confidence: 99%

Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis

2020

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Bladder cancer (BCa) is one of the most common malignancies and has a relatively poor outcome worldwide. However, the molecular mechanisms and processes of BCa development and progression remain poorly understood. Therefore, the present study aimed to identify candidate genes in the carcinogenesis and progression of BCa. Five GEO datasets and TCGA-BLCA datasets were analyzed by statistical software R, FUNRICH, Cytoscape, and online instruments to identify differentially expressed genes (DEGs), to construct protein‒protein interaction networks (PPIs) and perform functional enrichment analysis and survival analyses. In total, we found 418 DEGs. We found 14 hub genes, and gene ontology (GO) analysis revealed DEG enrichment in networks and pathways related to cell cycle and proliferation, but also in cell movement, receptor signaling, and viral carcinogenesis. Compared with noncancerous tissues, TPM1, CRYAB, and CASQ2 were significantly downregulated in BCa, and the other hub genes were significant upregulated. Furthermore, MAD2L1 and CASQ2 potentially play a pivotal role in lymph nodal metastasis. CRYAB and CASQ2 were both significantly correlated with overall survival (OS) and disease-free survival (DFS). The present study highlights an up to now unrecognized possible role of CASQ2 in cancer (BCa). Furthermore, CRYAB has never been described in BCa, but our study suggests that it may also be a candidate biomarker in BCa.

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“…A total of 3222 articles were retrieved from the database via the search strategy. Following the above inclusion and exclusion criteria, 36 articles [ 14 , 15 , 17 , 18 , 22 – 25 , 29 – 55 ] were enrolled in this meta-analysis (Fig. 1 ) and had 5198 cancer patients from China, Korea, Slovenia, Iran, Denmark, and Japan, who had been diagnosed with all types of solid tumors involving hepatocellular carcinoma (HCC), gastric cancer (GC), OSCC, esophageal squamous cell carcinoma (ESCC), cervical cancer, TSCC, breast carcinoma, colorectal carcinoma, gallbladder carcinoma, lung carcinoma, bladder carcinoma, anaplastic astrocytoma, prostate cancer, renal cell carcinoma, and so on.…”

Section: Resultsmentioning

confidence: 99%

“…[ 11 , 12 ] Further, the study inferred Oct4-positive cancer cells likely represent CSCs. [ 11 , 12 ] Other investigations have revealed that Oct4 is expressed abnormally in solid cancers, such as cervical carcinoma, [ 13 ] gastric carcinoma, [ 14 ] bladder carcinoma [ 15 ] among others.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of octamer binding transcription factor 4 for patients with solid tumors

Zhao¹,

Lu²,

Sun

et al. 2020

Medicine

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Background: Octamer binding transcription factor 4 (Oct4) is critically important in the development and progression of cancer, and is considered a potential biomarker for tumor prognosis. However, the prognostic value of Oct4 in patients with solid tumors remains elusive. Herein, we conducted a meta-analysis to assess the prognostic value of Oct4 in patients with solid tumors. Methods: We conducted a literature search on PubMed, Embase, and Web of Science databases to retrieve comprehensive and eligible studies published until December 2019. The study was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS)/progress-free survival (PFS) were used to evaluate the prognostic value of Oct4 in patients with solid tumors via either random or fixed-effects models. Results: In total, 36 studies with 5198 patients were included in the meta-analysis. Notably, elevated Oct4 expression was associated with worse OS (pooled HR: 2.02, 95% CI: 1.55–2.62, P < .001) and DFS/RFS/PFS (pooled HR: 2.34, 95% CI: 1.88–2.92, P < .001). Conclusion: This work demonstrated that patients with solid tumors show high expression of Oct4 which is linked to worse prognosis in patients with solid tumors including hepatocellular carcinoma (OS, DFS/RFS/PFS), esophageal squamous cell carcinoma (OS), gastric cancer (OS), cervical cancer (OS, DFS/RFS/PFS), and colorectal cancer (OS, DFS/RFS/PFS), this implicated Oct4 as a potential biomarker to predict the prognosis of tumors.

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Aberrant expression of KPNA2 is associated with a poor prognosis and contributes to OCT4 nuclear transportation in bladder cancer

Cited by 27 publications

References 30 publications

Integrative Bioinformatics Analysis of KPNA2 in Six Major Human Cancers

Integrative Bioinformatics Analysis of KPNA2 in Six Major Human Cancers

Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis

Prognostic value of octamer binding transcription factor 4 for patients with solid tumors

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