Liu Jun-Qi, Liao Xi-Wen, Wang Xiang-Kun, Yang Cheng-Kun, Zhou Xin, Liu Zheng-Qian, Han Quan-Fa, Fu Tian-Hao, Zhu Guang-Zhi, Han Chuang-Ye, Su Hao, Huang Jian-Lu, Ruan Guo-Tian, Yan Ling, Ye Xin-Ping, Peng Tao
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Shuang Yong Rd. 6#, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning, 530031, Guangxi Zhuang Autonomous Region, People's Republic of China.
BMC Gastroenterol. 2020 Dec 10;20(1):415. doi: 10.1186/s12876-020-01560-0.
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).
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.
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.
GPC2, GPC3, and GPC5 expression may serve as prognostic indicators in PDAC, and combination of these genes showed a higher efficiency for prognosis prediction.
本研究利用来自癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的数据，探讨了磷脂酰肌醇蛋白聚糖（GPC）家族基因在胰十二指肠切除术后胰腺导管腺癌（PDAC）患者中的预后意义。
分析共纳入了来自TCGA的112例PDAC患者和来自GEO的48例患者。采用Kaplan-Meier法和对数秩检验分析总生存期与GPC家族基因表达以及基本临床特征之间的关系。进行联合效应生存分析以进一步检验GPC基因与预后之间的关系。基于临床特征和预后相关基因建立了预后列线图。通过全基因组共表达分析研究预后相关基因，并进行基因集富集分析（GSEA）以确定这些基因影响预后的潜在机制。
在TCGA数据库中，GPC2、GPC3和GPC5的高表达与良好的生存期显著相关（对数秩P值分别为0 . 031、0 . 021和0 . 028；校正P值分别为0 . 005、0 . 022和0 . 020），并且这些基因的联合效应分析对预后预测有效。应用预后列线图通过计算的总分来预测生存概率。全基因组共表达和GSEA分析表明，GPC2可能通过序列特异性DNA结合、蛋白质转运、细胞分化和致癌特征（KRAS、RAF、STK33和VEGFA）影响预后。GPC3可能与细胞黏附、血管生成、炎症反应、Ras、Rap1、PI3K-Akt等信号通路、趋化因子、GPCR以及细胞周期蛋白D1、p53、PTEN等特征有关。GPC5可能参与转录因子复合物、TFRC1、致癌特征（HOXA9和BMI1）、基因甲基化、磷脂代谢过程、甘油磷脂代谢、细胞周期和EGFR通路。
GPC2、GPC3和GPC5的表达可能作为PDAC的预后指标，这些基因的联合使用对预后预测具有更高的效率。
