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通过共表达网络识别肝转移相关基因,构建预测胰腺导管腺癌患者预后的 5 基因模型

英文原题:Identifying Liver Metastasis-Related Genes Through a Coexpression Network to Construct a 5-Gene Model for Predicting Pancreatic Ductal Adenocarcinoma Patient Prognosis.

查看英文原题

Identifying Liver Metastasis-Related Genes Through a Coexpression Network to Construct a 5-Gene Model for Predicting Pancreatic Ductal Adenocarcinoma Patient Prognosis.

PubMed 2023/02/01(内容时间) Pancreas Q3 · IF 2.2(JCR 2025)

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研究概要

所开发的 LMPI 核心基因可能是预测胰腺导管腺癌预后、免疫特征及免疫治疗疗效的独立因素。

研究思路结论见上方概要

本研究旨在开发一个肝转移相关基因预后指数(LMPI),用于胰腺导管腺癌的预后和治疗。

癌症基因组图谱数据集通过加权基因共表达网络分析用于识别肝转移相关枢纽基因。鉴定核心基因以使用Cox回归方法构建LMPI。应用免疫细胞丰度标识符以确定免疫细胞丰度。

在黑模块中,共有78个与肝转移相关的枢纽基因显著富集于补体和凝血级联、脂肪消化吸收以及PPAR信号通路。随后,基于5个预后基因(MOGAT3、ASGR1、TRPM8、SGSM1和LOC101927851)构建了LMPI。LMPI评分较高的患者总生存期较差,驱动基因突变的共存或互斥对更多,且从免疫治疗中获益少于LMPI评分较低的患者。此外,还发现LMPI评分与免疫浸润之间存在高度相关性,如CD4初始T细胞、CD8 T细胞、细胞毒性T细胞、辅助性T细胞2、滤泡辅助性T细胞和NK 细胞。

展开英文摘要原文

This study aimed to develop a liver metastasis-related gene prognostic index (LMPI) for pancreatic ductal adenocarcinoma prognosis and therapy.

The Cancer Genome Atlas data set was used to identify liver metastasis-related hub genes via weighted gene coexpression network analysis. The core genes were identified to construct an LMPI by using the Cox regression method. An immune cell abundance identifier was applied to determine the immune cell abundance.

A total of 78 hub liver metastasis-related genes in the black module were significantly enriched in complement and coagulation cascades, fat digestion and absorption, and the PPAR signaling pathway. Then, an LMPI was constructed on the basis of the 5 prognostic genes (MOGAT3, ASGR1, TRPM8, SGSM1, and LOC101927851). Patients with higher LMPI scores had poor overall survival, more co-occurring or mutually exclusive pairs of driver gene mutations, and less benefit from immunotherapy than patients with lower LMPI scores. In addition, a high correlation was also found between LMPI scores and immune infiltration, such as CD4 naive, CD8 T, cytotoxic T, T helper 2, follicular helper T, and natural killer cells.

The core genes of the LMPI developed may be independent factors for predicting prognosis, immune characteristics, and immunotherapy efficacy in pancreatic ductal adenocarcinoma.

论文信息

作者
Liu T、Chen J、Liu AA、Chen L、Liang X、Peng JF、Zheng MH、Li JD
通讯作者单位
Department of Pancreatic-biliary Surgery, Changzheng Hospital, Navy Medical University, Shanghai.China
文献类型
非美国政府资助研究
期刊
Pancreas2023 Feb 1
原文标识
PubMed 37523607 · DOI 10.1097/MPA.0000000000002229