期刊
BMC GASTROENTEROLOGY
卷 20, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12876-020-01560-0
关键词
GPC family genes; Pancreatic ductal adenocarcinoma; Prognostic indicator; Mechanism
资金
- National Natural Science Foundation of China [81560535, 81802874, 81072321, 30760243, 30460143, 30560133]
- Natural Science Foundation of Guangxi Province of China [2017JJB140189y, 2018GXNSFAA050119]
- 2009 Program for New Century Excellent Talents in University (NCET)
- Guangxi Natural Sciences Foundation [GuiKeGong 1104003A-7]
- Guangxi Health Ministry Medicine Grant [Z201018]
- Scientific Research Fund of the Health and Family Planning Commission of Guangxi Zhuang Autonomous Region [Z2016318, Z2016307]
- Guangxi Key RD Program [GKEAB18221019]
- Basic Ability Improvement Project for Middle-aged and Young Teachers in Colleges and Universities in Guangxi [2018KY0110]
- Innovation Project of Guangxi Graduate Education [JGY2018037]
- 2018 Innovation Project of Guangxi Graduate Education [YCBZ2018036]
- Guangxi Key Laboratory for the Prevention and Control of Viral Hepatitis [GXCDCKL201902]
- Research Institute of Innovative Think-tank in Guangxi Medical University (The gene-environment interaction in hepatocarcinogenesis in Guangxi HCCs and its translational applications in the HCC prevention)
- Key laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education [GKE2018-01, GKE2019-11]
Background This 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). Methods A 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. Results In 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. Conclusion GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.
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