Establishment and Validation of Lactate Metabolism-Related Genes as a Prognostic Model for Gastric Cancer.

IF 2.2 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Current molecular medicine Pub Date : 2024-05-09 DOI:10.2174/0115665240290237240424054233

Jinyu Hu, Qinxuan Xu, Yuchang Fei, Zhengwei Tan, Lei Pan

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Abstract

Background: Gastric Cancer (GC) has become one of the most important causes of cancer-related deaths worldwide due to its intractability. Studying the mechanisms of gastric carcinogenesis, recurrence, and metastasis, and searching for new therapeutic targets have become the main directions of today's gastric cancer research. Lactate is considered a metabolic by-product of tumor aerobic glycolysis, which can regulate tumor development through various mechanisms, including cell cycle regulation, immunosuppression, and energy metabolism. However, the effects of genes related to lactate metabolism on the prognosis and tumor microenvironmental characteristics of GC patients are unknown.

Method: In this study, we have collected gene expression data of gastric cancer from The Cancer Genome Atlas (TCGA) and identified differentially expressed genes in gastric cancer using the "Limma" software package.

Result: 76 differentially expressed lactate metabolism-related genes were screened, and then the Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analysis were employed that identified 8 genes, constructed Lactate Metabolism-related gene signals (LMRs), and verified the reliability of the prognostic risk mapping by using TCGA training set and TCGA internal test set. Finally, the functional enrichment analysis was employed to identify the molecular mechanism.

Conclusion: Eight lactate metabolism-related genes were constructed into a new predictive signal that better predicted the overall survival of gastric cancer patients and can guide clinical decisions for more precise and personalized treatment.

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乳酸代谢相关基因作为胃癌预后模型的建立和验证

背景：胃癌（GC）因其难治性已成为全球癌症相关死亡的最重要原因之一。研究胃癌发生、复发和转移的机制以及寻找新的治疗靶点已成为当今胃癌研究的主要方向。乳酸被认为是肿瘤有氧糖酵解的代谢副产物，可通过细胞周期调节、免疫抑制和能量代谢等多种机制调控肿瘤的发展。然而，乳酸代谢相关基因对 GC 患者预后和肿瘤微环境特征的影响尚不清楚。研究方法本研究从癌症基因组图谱（TCGA）中收集了胃癌的基因表达数据，并使用 "Limma "软件包鉴定了胃癌中的差异表达基因。结果：筛选出76个差异表达的乳酸代谢相关基因，然后采用最小绝对收缩和选择操作器（LASSO）和Cox回归分析鉴定出8个基因，构建了乳酸代谢相关基因信号（LMRs），并利用TCGA训练集和TCGA内部测试集验证了预后风险图谱的可靠性。最后，利用功能富集分析确定了分子机制。结论8个乳酸代谢相关基因被构建成一个新的预测信号，该信号能更好地预测胃癌患者的总生存期，并能指导临床决策，实现更精准的个性化治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular medicine 医学-医学：研究与实验

CiteScore

5.00

自引率

4.00%

发文量

141

审稿时长

4-8 weeks

期刊介绍： Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.