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胃腺癌预后代谢特征的建立。

Development of a prognostic metabolic signature in stomach adenocarcinoma.

机构信息

Department of Gastrointestinal Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, 68 GeHu Road, Changzhou, 213000, Jiangsu, China.

Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, 213000, China.

出版信息

Clin Transl Oncol. 2022 Aug;24(8):1615-1630. doi: 10.1007/s12094-022-02809-8. Epub 2022 Mar 30.

Abstract

PURPOSE

The growth and aggressiveness of Stomach adenocarcinoma (STAD) is significantly affected by basic metabolic changes. This study aimed to identify metabolic gene prognostic signatures in STAD.

METHODS

An integrative analysis of datasets from the Cancer Genome Atlas and Gene Expression Omnibus was performed. A metabolic gene prognostic signature was developed using univariable Cox regression and Kaplan-Meier survival analysis. A nomogram model was developed to predict the prognosis of STAD patients. Finally, Gene Set Enrichment Analysis (GESA) was used to explore the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways significantly associated with the risk grouping.

RESULTS

A total of 327 metabolism-related differentially expressed genes were identified. Three subtypes of STAD were identified and nine immune cell types, including memory B cell, resting and activated CD4+ memory T cells, were significantly different among the three subgroups. A risk score model including nine survival-related genes which could separate high-risk patients from low-risk patients was developed. The prognosis of STAD patients likely benefited from lower expression levels of genes, including ABCG4, ABCA6, GPX8, KYNU, ST8SIA5, and CYP19A1. Age, radiation therapy, tumor recurrence, and risk score model status were found to be independent risk factors for STAD and were used for developing a nomogram. Nine KEGG pathways, including spliceosome, pentose phosphate pathway, and citrate TCA cycle were significantly enriched in GESA.

CONCLUSION

We propose a metabolic gene signature and a nomogram for STAD which might be used for predicting the survival of STAD patients and exploring prognostic markers.

摘要

目的

胃腺癌(STAD)的生长和侵袭性受基础代谢变化的显著影响。本研究旨在鉴定 STAD 中的代谢基因预后特征。

方法

对癌症基因组图谱和基因表达综合分析数据库进行整合分析。采用单变量 Cox 回归和 Kaplan-Meier 生存分析构建代谢基因预后特征。构建诺莫图模型预测 STAD 患者的预后。最后,采用基因集富集分析(GSEA)探索与风险分组显著相关的京都基因与基因组百科全书(KEGG)通路。

结果

共鉴定出 327 个与代谢相关的差异表达基因。鉴定出 3 种 STAD 亚型,其中 9 种免疫细胞类型,包括记忆 B 细胞、静息和激活的 CD4+记忆 T 细胞,在这 3 个亚组中存在显著差异。构建了一个包含 9 个与生存相关的基因的风险评分模型,该模型可以将高危患者与低危患者区分开来。STAD 患者的预后可能受益于包括 ABCG4、ABCA6、GPX8、KYNU、ST8SIA5 和 CYP19A1 在内的基因表达水平较低。年龄、放疗、肿瘤复发和风险评分模型状态被发现是 STAD 的独立危险因素,并用于构建诺莫图。GSEA 分析发现 9 条 KEGG 通路,包括剪接体、戊糖磷酸途径和柠檬酸 TCA 循环,显著富集。

结论

本研究提出了一个 STAD 的代谢基因特征和诺莫图模型,可用于预测 STAD 患者的生存情况并探索预后标志物。

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