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通过共表达分析鉴定预测胃癌腹膜转移的关键基因和通路

Identification of Key Gene and Pathways for the Prediction of Peritoneal Metastasis of Gastric Cancer by Co-expression Analysis.

作者信息

Zhang Simeng, Zang Dan, Cheng Yu, Li Zhi, Yang Bowen, Guo Tianshu, Liu Yunpeng, Qu Xiujuan, Che Xiaofang

机构信息

Department of Medical Oncology, the First Hospital of China Medical University, Shenyang 110001, China.

Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China.

出版信息

J Cancer. 2020 Mar 4;11(10):3041-3051. doi: 10.7150/jca.39645. eCollection 2020.

Abstract

Peritoneal metastasis is the most common pattern in advanced gastric cancer and can predict poor disease prognosis. Early detection of peritoneal tumor dissemination is restricted by small peritoneal deposits. Therefore, it is critical to identify a novel predictive marker and to explore the potential mechanism associated with this process. In the present study, one module that correlated with peritoneal metastasis was identified. Enrichment analysis indicated that the Focal adhesion and the PI3K-Akt signaling pathway were the most significant pathways. Following network and Molecular Complex Detection (MCODE) analysis, the hub-gene cluster that consisted of 19 genes was selected. Methionine sulfoxide reductase B3 () was identified as a seed gene. Survival analysis indicated that high expression levels of were independent predictors of peritoneal disease-free survival (pDFS) as determined by univariate (HR 8.559, 95% CI; 3.339-21.937; P<.001) and multivariate Cox analysis (HR 3.982, 95% CI; 1.509-10.509; P=.005). Furthermore, patients with high levels of exhibited a significantly lower Overall Survival (OS) (log-rank P = 0.007). The external validation was performed by the (The Cancer Genome Atlas (TCGA)) (log-rank P = 0.037) and Kaplan Meier-plotter (KMplotter) (log-rank P = 0.031) data. experiments confirmed that MSRB3 was a critical protein in regulating gastric cancer cell proliferation and migration. In conclusion, High expression levels of in GC can predict peritoneal metastasis and recurrence as well as poor prognosis. Furthermore, was involved in the regulation of the proliferation and migration of GC cells.

摘要

腹膜转移是晚期胃癌最常见的转移方式,可预测疾病预后不良。早期检测腹膜肿瘤播散受限于微小的腹膜沉积物。因此,识别一种新的预测标志物并探索与该过程相关的潜在机制至关重要。在本研究中,确定了一个与腹膜转移相关的模块。富集分析表明,粘着斑和PI3K-Akt信号通路是最显著的通路。经过网络和分子复合物检测(MCODE)分析,选择了由19个基因组成的枢纽基因簇。甲硫氨酸亚砜还原酶B3()被确定为种子基因。生存分析表明,由单因素(HR 8.559,95%CI;3.339-21.937;P<0.001)和多因素Cox分析(HR 3.982,95%CI;1.509-10.509;P=0.005)确定,高水平的是腹膜无病生存期(pDFS)的独立预测因子。此外,高水平的患者总生存期(OS)显著较低(对数秩检验P = 0.007)。通过癌症基因组图谱(TCGA)(对数秩检验P = 0.037)和Kaplan Meier绘图仪(KMplotter)(对数秩检验P = 0.031)数据进行外部验证。实验证实MSRB3是调节胃癌细胞增殖和迁移的关键蛋白。总之,胃癌中高水平的可预测腹膜转移、复发以及预后不良。此外,参与了胃癌细胞增殖和迁移的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/719d/7086253/ba072a625624/jcav11p3041g001.jpg

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