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Combining bioinformatics techniques to explore the molecular mechanisms involved in pancreatic cancer metastasis and prognosis

胰腺癌 转移 癌症研究 基因表达谱 基因 生物 PI3K/AKT/mTOR通路 癌症 CA19-9号 信号转导 蛋白激酶B 生物信息学 基因表达 肿瘤科 内科学 医学 遗传学
作者
Jia‐Sheng Xu,Kaili Liao,Xinlu Wang,Jiarui He,Xiaozhong Wang
出处
期刊:Journal of Cellular and Molecular Medicine [Wiley]
卷期号:24 (24): 14128-14138 被引量:24
标识
DOI:10.1111/jcmm.16023
摘要

Abstract This article aims to explore the underlying molecular mechanisms and prognosis‐related genes in pancreatic cancer metastasis. Pancreatic cancer metastasis‐related gene chip data were downloaded from GENE EXPRESSION OMNIBUS(GEO)database. Differentially expressed genes were screened after R‐package pre‐treatment. Functional annotations and related signalling pathways were analysed using DAVID software. GEPIA (Gene Expression Profiling Interactive Analysis) was used to perform prognostic analysis, and differential genes associated with prognosis were screened and validated using data from GEO. We screened 40 healthy patients, 40 primary pancreatic cancer and 40 metastatic pancreatic cancer patients, collected serum, designed primers and used qPCR to test the expression of prognosis‐related genes in each group. 109 differentially expressed genes related with pancreatic cancer metastasis were screened, of which 49 were up‐regulated and 60 were down‐regulated. Functional annotation and pathway analysis revealed differentially expressed genes were mainly concentrated in protein activation cascade, extracellular matrix construction, decomposition, etc In the biological process, it is mainly involved in signalling pathways such as PPAR, PI3K‐Akt and ECM receptor interaction. Prognostic analysis showed the expression levels of four genes were significantly correlated with the overall survival time of patients with pancreatic cancer, namely SCG5, CRYBA2, CPE and CHGB. qPCR experiments showed the expression of these four genes was decreased in both the primary pancreatic cancer group and the metastatic pancreatic cancer group, and the latter was more significantly reduced. Pancreatic cancer metastasis is closely related to the activation of PPAR pathway, PI3K‐Akt pathway and ECM receptor interaction. SCG5, CRYBA2, CPE and CHGB genes are associated with the prognosis of pancreatic cancer, and their low expression suggests a poor prognosis.
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