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Downregulation of KIF1B mRNA in hepatocellular carcinoma tissues correlates with poor prognosis.

ABSTRACT: To compare kinesin family member 1B (KIF1B) expression with clinicopathologic parameters and prognosis in hepatocellular carcinoma (HCC) patients.KIF1B protein and mRNA expression was assessed in HCC and paracarcinomatous (PC) tissues from 68 patients with HCC using Western blot and quantitative real-time reverse transcription-PCR, respectively. Student's t-tests were used to analyze relationships between clinicopathologic parameters and KIF1B expression, the Kaplan-Meier method was used to analyze survival outcomes, and the log-rank test was used to compare survival differences between groups.Mean protein and mRNA levels of KIF1B were similar between HCC and PC tissues. However, HCC tissues with vein invasions had significantly lower KIF1B protein levels compared to those without vein invasions (2.30 ± 0.82 relative units vs 2.77 ± 0.84 relative units, P < 0.05). KIF1B protein levels in HCC tissues from patients with recurrence during the follow-up period were significantly lower than those without recurrence (2.31 ± 0.92 relative units vs 2.80 ± 0.80 relative units, P < 0.05). However, KIF1B protein and mRNA expression in HCC patients was not associated with other clinicopathologic parameters. Ratios of KIF1B mRNA expression in HCC tissues to those in PC tissues were correlated with overall survival (13.5 mo vs 20.0 mo, P < 0.05) and disease-free survival (11.5 mo vs 19.5 mo, P < 0.05).Downregulation of KIF1B in HCC tissues is associated with poor prognosis; additional clinical studies are needed to confirm whether KIF1B can serve as a prognostic marker.

SUBMITTER: Yang SZ

PROVIDER: S-EPMC4507112 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Downregulation of KIF1B mRNA in hepatocellular carcinoma tissues correlates with poor prognosis.

Yang Song-Zhu SZ Wang Jian-Tao JT Yu Wei-Wei WW Liu Qing Q Wu Yan-Fang YF Chen Shu-Guang SG

World journal of gastroenterology 20150701 27

<h4>Aim</h4>To compare kinesin family member 1B (KIF1B) expression with clinicopathologic parameters and prognosis in hepatocellular carcinoma (HCC) patients.<h4>Methods</h4>KIF1B protein and mRNA expression was assessed in HCC and paracarcinomatous (PC) tissues from 68 patients with HCC using Western blot and quantitative real-time reverse transcription-PCR, respectively. Student's t-tests were used to analyze relationships between clinicopathologic parameters and KIF1B expression, the Kaplan-M ...[more]

PMID: 26217094

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Project description:Objective:Hepatocellular carcinoma (HCC) is a disease that is associated with high mortality; currently, there is no curative and reliable treatment. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) is the key signaling molecule in the wingless and INT-1/planar cell polarity (WNT/PCP) pathway. This study aimed to elucidate the prognostic significance of CELSR3 in HCC patients. Methods:The Cancer Genome Atlas (TCGA) database, the Cancer Cell Line Encyclopedia (CCLE) database and the Gene Expression Omnibus (GEO) database were used to analyze the expression of CELSR3 mRNA in HCC samples and cells. The relationship between CELSR3 mRNA and clinical features was assessed by the chi-square test. the diagnostic and predictive value of CELSR3 mRNA expression were analyzed using the receiver operating characteristic (ROC) curve. Kaplan-Meier curve and Cox regression analyses were performed to assess the prognostic value of CELSR3 mRNA in HCC patients. Finally, all three cohorts database was used for gene set enrichment analysis(GSEA) and the identification of CELSR3-related signal transduction pathways. Results:The expression of CELSR3 mRNA was upregulated in HCC, and its expression was correlated with age (P = 0.025), tumor status (P = 0.022), clinical stage (P = 0.003), T classification (P = 0.010), vital status (P = 0.001), and relapse (P = 0.005). The ROC curve assessment indicated that CELSR3 mRNA expression has high diagnostic value in HCC and in the subgroup analysis of stage. In addition, the Kaplan-Meier curve and Cox analyses suggested that patients with high CELSR3 mRNA expression have a poor prognosis, indicating that CELSR3 mRNA is an independent prognostic factor for the overall survival of HCC patients. GSEA showed that GO somatic diversification of immune receptors, GO endonuclease activity, GO DNA repair complex and GO somatic cell DNA recombination, were differentially enriched in the meta-GEO cohort, the HCC cell line cohort and the TCGA cohort of the high CELSR3 mRNA expression phenotype. Conclusion:Our results indicate that CELSR3 mRNA is involved in the progression of cancer and can be used as a biomarker for the prognosis of HCC patients.

Project description:BackgroundNDC1 was identified to be a tumor-promoting factor in non-small cell lung cancer and cervical cancer. However, no report had clarified the relationship between NDC1 and hepatocellular carcinoma (HCC). In this paper, we explored the expression and potential functions of NDC1 in HCC for the first time through the rational application of bioinformatics and relevant basic experiments.MethodsNDC1-related expression profiles and clinical data of HCC patients were collected from The Cancer Genome Atlas (TCGA) database, which were verified via quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Univariate and multivariate Cox regression analyses were used to identify NDC1 as an independent factor for HCC prognosis, and NDC1-related signaling pathways were determined by gene set enrichment analysis (GSEA). Furthermore, we deeply probed the potential links of NDC1 to immunity and immune response. Finally, the bioeffects and underlying mechanisms of ectopic NDC1 overexpression and depletion were determined in HepG2 cells by immunoblotting, flow cytometry, Cell-Counting-Kit-8 (CCK-8), and EDU (5-Ethynyl-2'-deoxyuridine).ResultsUp-regulated expression of NDC1 was detected by means of the TCGA database, which was consistent with the results obtained from further qRT-PCR, immunohistochemistry and the CPTAC database. Kaplan-Meier (K-M) survival analysis revealed a worse prognosis in HCC patients with high NDC1 expression. Besides, NDC1 was certified to be closely linked to tumor histologic grade, clinical stage and T stage. Moreover, univariate and multivariate Cox regression analyses defined NDC1 as an independent element for HCC prognosis. NDC1-related signaling pathways, utilizing GSEA analysis, were subsequently found out. What's more, NDC1 expression was detected to be enormously associated with microsatellite instability (MSI), immune cell infiltration, immune checkpoint molecules and immune cell pathways. As for immunotherapy, we discovered that different risk groups tended to have different immune checkpoint inhibitor responses, which indicated crucial implication value of NDC1 for HCC immunotherapy. More interestingly, we observed that the overexpression of NDC1 could promote the migration and invasion of HCC cells.ConclusionsOur article demonstrated that NDC1 might serve as a valuable predictor in the prognosis and immunotherapy of HCC. NDC1 played an oncogenic role in HCC.

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Downregulation of KIF1B mRNA in hepatocellular carcinoma tissues correlates with poor prognosis.

Publications

Downregulation of KIF1B mRNA in hepatocellular carcinoma tissues correlates with poor prognosis.

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