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Prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy.

ABSTRACT: BACKGROUND:The aim of this study was to investigate the potential prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma (PDAC) patients after pancreaticoduodenectomy. METHODS:Kaplan-Meier survival analysis method with log-rank test and Cox proportional hazards regression analysis were performed to figure out the association between Kinesin-4 family genes expression and PDAC patients overall survival time. Joint-effect survival analysis and stratified survival analysis were carried out to assess the prognosis prediction value of prognosis-related gene. Nomogram was constructed for the individualized prognosis prediction. In addition, we had used the gene set enrichment analysis and genome-wide co-expression analysis to further explore the potential mechanism. RESULTS:KIF21A expression level was significantly associated with PDAC patient clinical prognosis outcome and patient with a high expression of KIF21A would have a shorter overall survival time. The prognosis prediction significance of KIF21A was well validated by the joint-effect survival analysis, stratified survival analysis, and nomogram. Meanwhile, the gene set enrichment analysis and genome-wide co-expression analysis revealed that KIF21A might involve in DNA damage and repair, transcription and translation process, post-translation protein modification, cell cycle, carcinogensis genes and pathways. CONCLUSIONS:Our current research demonstrated that KIF21A could serve as a potential prognostic biomarker for patient with early-stage PDAC after pancreaticoduodenectomy.

SUBMITTER: Han Q

PROVIDER: S-EPMC6826000 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy.

Han Quanfa Q Han Chuangye C Liao Xiwen X Huang Ketuan K Wang Xiangkun X Yu Tingdong T Yang Chengkun C Li Guanghui G Han Bowen B Zhu Guangzhi G Liu Zhengqian Z Zhou Xin X Liu Junqi J Su Hao H Shang Liming L Peng Tao T Ye Xinping X

Cancer medicine 20190906 15

<h4>Background</h4>The aim of this study was to investigate the potential prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma (PDAC) patients after pancreaticoduodenectomy.<h4>Methods</h4>Kaplan-Meier survival analysis method with log-rank test and Cox proportional hazards regression analysis were performed to figure out the association between Kinesin-4 family genes expression and PDAC patients overall survival time. Joint-effect survival a ...[more]

PMID: 31489986

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Project description:BackgroundThis study explored the prognostic significance of Glypican (GPC) family genes in patients with pancreatic ductal adenocarcinoma (PDAC) after pancreaticoduodenectomy using data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).MethodsA total of 112 PDAC patients from TCGA and 48 patients from GEO were included in the analysis. The relationship between overall survival and the expression of GPC family genes as well as basic clinical characteristics was analyzed using the Kaplan-Meier method with the log-rank test. Joint effects survival analysis was performed to further examine the relationship between GPC genes and prognosis. A prognosis nomogram was established based on clinical characteristics and prognosis-related genes. Prognosis-related genes were investigated by genome-wide co-expression analysis and gene set enrichment analysis (GSEA) was carried out to identify potential mechanisms of these genes affecting prognosis.ResultsIn TCGA database, high expression of GPC2, GPC3, and GPC5 was significantly associated with favorable survival (log-rank P = 0.031, 0.021, and 0.028, respectively; adjusted P value = 0.005, 0.022, and 0.020, respectively), and joint effects analysis of these genes was effective for prognosis prediction. The prognosis nomogram was applied to predict the survival probability using the total scores calculated. Genome-wide co-expression and GSEA analysis suggested that the GPC2 may affect prognosis through sequence-specific DNA binding, protein transport, cell differentiation and oncogenic signatures (KRAS, RAF, STK33, and VEGFA). GPC3 may be related to cell adhesion, angiogenesis, inflammatory response, signaling pathways like Ras, Rap1, PI3K-Akt, chemokine, GPCR, and signatures like cyclin D1, p53, PTEN. GPC5 may be involved in transcription factor complex, TFRC1, oncogenic signatures (HOXA9 and BMI1), gene methylation, phospholipid metabolic process, glycerophospholipid metabolism, cell cycle, and EGFR pathway.ConclusionGPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.

Project description:Pancreatic ductal adenocarcinoma (PDAC) is characterized by fast tumor progression and diagnosis at advanced, inoperable stages. Previous studies could demonstrate an involvement of miR-192-5p in epigenetic regulation of visceral carcinomas. Due to contradictory results, however, the clinical utility of miR-192-5p in PDAC has yet to be determined. MiR-192-5p expression was analyzed by RT-qRT-PCR in human PDAC and benign tissue (n = 78), blood serum (n = 81) and serum exosomes (n = 74), as well as in PDAC cell lines (n = 5), chemoresistant cell clones (n = 2), and pancreatic duct cell line H6c7. Analysis of EMT-associated (epithelial-to-mesenchymal transition) proteins was performed by immunohistochemistry and Western blot. MiR-192-5p was deregulated in PDAC as compared to healthy controls (HCs), with downregulation in macrodissected tissue (p < 0.001) and upregulation in blood serum of PDAC UICC (Union for International Cancer Control) stage IV (p = 0.016) and serum exosomes of PDAC UICC stages II to IV (p < 0.001). MiR-192-5p expression in tumor tissue was significantly lower as compared to corresponding peritumoral tissue (PDAC UICC stage II: p < 0.001; PDAC UICC stage III: p = 0.024), while EMT markers ZEB1 and ZEB2 were more frequently expressed in tumor tissue as compared to peritumoral tissue, HCs, and chronic pancreatitis. Tissue-derived (AUC of 0.86; p < 0.0001) and exosomal (AUC of 0.83; p = 0.0004) miR-192-5p could differentiate between PDAC and HCs with good accuracy. Furthermore, high expression of miR-192-5p in PDAC tissue of curatively resected PDAC patients correlated with prolonged overall and recurrence-free survival in multivariate analysis. In vitro, miR-192-5p was downregulated in gemcitabine-resistant cell clones of AsPC-1 (p = 0.029). Transient transfection of MIA PaCa-2 cells with miR-192-5p mimic resulted in downregulation of ZEB2. MiR-192-5p seems to possess a tumor-suppressive role and high potential as a diagnostic and prognostic marker in PDAC.

Dataset Information

Prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy.

Publications

Prognostic value of Kinesin-4 family genes mRNA expression in early-stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy.

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