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不同治疗方案下胃癌患者胶原基因表达的改变及其预后价值。

Alteration and prognostic values of collagen gene expression in patients with gastric cancer under different treatments.

机构信息

Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, China.

Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, China.

出版信息

Pathol Res Pract. 2020 Mar;216(3):152831. doi: 10.1016/j.prp.2020.152831. Epub 2020 Jan 24.

Abstract

Collagen (COL) genes participate in tumor extracellular matrix (ECM)-receptor interactions and focal adhesion pathways, which play a crucial role in tumor invasion and metastasis. The prognostic value of COL genes has been shown for several malignancies. In the present study, we analyzed multiple microarray datasets using the Oncomine database to identify alterations of COL genes in gastric cancer (GC). Gene expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) in GC tissues and matched adjacent tissues. The prognostic value of differentially expressed COL genes in GC was evaluated by Kaplan-Meier survival analysis based on the complete mRNA transcriptomics data from The Cancer Genome Atlas (TCGA). We found that seven COL genes (COL1A2, COL4A1, COL4A2, COL6A1, COL6A2, COL6A3, and COL11A1) were elevated in GC. Among them, stepwise multivariate Cox regression was applied, and it was determined that COL4A1 and COL4A2 were signature and independent prognostic biomarkers in GC patients with obviously different overall survival (OS). High expression of COL4A1, COL4A2, COL6A1, COL6A2, and COL6A3 was correlated with poorer prognosis of GC patients treated by surgery only, while higher expression of COL4A1 and COL11A1 correlated with poorer survival of patients treated by 5-fluorouracil-based adjuvant therapy. Our results indicate that overexpression of COL genes might be utilized as novel prognostic markers for GC and assist with therapy selection.

摘要

胶原(COL)基因参与肿瘤细胞外基质(ECM)-受体相互作用和黏着斑途径,这些途径在肿瘤侵袭和转移中起着至关重要的作用。COL 基因的预后价值已在多种恶性肿瘤中得到证实。在本研究中,我们使用 Oncomine 数据库分析了多个微阵列数据集,以确定胃癌(GC)中 COL 基因的改变。通过定量实时聚合酶链反应(qRT-PCR)和免疫组织化学(IHC)分析 GC 组织和配对的相邻组织中的基因表达水平。基于癌症基因组图谱(TCGA)的完整 mRNA 转录组学数据,通过 Kaplan-Meier 生存分析评估差异表达 COL 基因在 GC 中的预后价值。我们发现 COL1A2、COL4A1、COL4A2、COL6A1、COL6A2、COL6A3 和 COL11A1 这 7 个 COL 基因在 GC 中上调。其中,采用逐步多变量 Cox 回归分析,确定 COL4A1 和 COL4A2 是 GC 患者的标志性和独立预后生物标志物,其总生存(OS)明显不同。COL4A1、COL4A2、COL6A1、COL6A2 和 COL6A3 的高表达与仅接受手术治疗的 GC 患者预后较差相关,而 COL4A1 和 COL11A1 的高表达与接受 5-氟尿嘧啶辅助治疗的患者生存较差相关。我们的结果表明,COL 基因的过表达可能被用作 GC 的新型预后标志物,并有助于治疗选择。

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