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胰腺癌中能量代谢相关基因的预后特征构建

Prognostic signature construction of energy metabolism-related genes in pancreatic cancer.

作者信息

Liu Hao, Zhang Jianhua, Wei Chaoguang, Liu Zhao, Zhou Wei, Yang Pan, Gong Yifu, Zhao Yuxiang

机构信息

Key Laboratory of Marine Biotechnology of Zhejiang Province, School of Marine Sciences, Ningbo University, Ningbo, China.

College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Front Oncol. 2022 Sep 29;12:917897. doi: 10.3389/fonc.2022.917897. eCollection 2022.

Abstract

Pancreatic cancer is the 7th leading cause of cancer death worldwide, and its incidence and mortality rate have been on the rise in recent years in Western developed countries. The specificity of the disease and the lack of appropriate treatments have resulted in a 5-year overall survival rate of only 9%. In this study, we conducted a study based on the TCGA database and GEO database and analyzed using the energy metabolism gene set to establish a prognostic model with the least absolute shrinkage and selection operator to identify 7-genes prognostic signature, and the gene expression was verified by Real-time PCR. The model was validated using a risk score calculation, and the OS rates of the 7 genes were analyzed using one-way Cox regression. The prognostic relationship between vesicle-associated membrane protein 2 (VAMP2) and pancreatic cancer patients was analyzed by OS and progression-free survival, and the prognosis was found to be significantly worse in the high-expression group. A Nomogram showed that VAMP2 was an independent prognostic factor in pancreatic cancer. Gene set enrichment analysis showed that VAMP2 upregulation was enriched in pathways associated with immune response and that VAMP2 downregulation was enriched in metabolism-related pathways. The association of VAMP2 with immune cell infiltration was analyzed for the enrichment results, and VAMP2 was found to be positively associated with all 6 immune cells. The results of this study suggest that VAMP2 is an independent prognostic factor associated with energy metabolism in pancreatic cancer and may be involved in the immune response.

摘要

胰腺癌是全球癌症死亡的第七大主要原因,近年来在西方发达国家,其发病率和死亡率一直在上升。该疾病的特殊性以及缺乏合适的治疗方法导致其5年总生存率仅为9%。在本研究中,我们基于TCGA数据库和GEO数据库进行研究,并使用能量代谢基因集进行分析,以建立具有最小绝对收缩和选择算子的预后模型,从而识别7基因预后特征,并通过实时PCR验证基因表达。使用风险评分计算对模型进行验证,并使用单向Cox回归分析这7个基因的总生存率。通过总生存期和无进展生存期分析囊泡相关膜蛋白2(VAMP2)与胰腺癌患者之间的预后关系,发现高表达组的预后明显更差。列线图显示VAMP2是胰腺癌的独立预后因素。基因集富集分析表明,VAMP2上调在与免疫反应相关的通路中富集,而VAMP2下调在与代谢相关的通路中富集。针对富集结果分析VAMP2与免疫细胞浸润的关联,发现VAMP2与所有6种免疫细胞呈正相关。本研究结果表明,VAMP2是胰腺癌中与能量代谢相关的独立预后因素,可能参与免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcd2/9559226/932d1e318a37/fonc-12-917897-g001.jpg

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