Evaluating lactate metabolism for prognostic assessment and therapy response prediction in gastric cancer with emphasis on the oncogenic role of SLC5A12

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. General subjects Pub Date : 2025-02-01 DOI:10.1016/j.bbagen.2024.130739

Chenyi Lin , Jianjian Ye , Chao Xu , Ying Zheng , Yining Xu , Yuluo Chen , Liangjie Chi , Jia Lin , Feng Li , Yao Lin , Qingshui Wang

{"title":"Evaluating lactate metabolism for prognostic assessment and therapy response prediction in gastric cancer with emphasis on the oncogenic role of SLC5A12","authors":"Chenyi Lin , Jianjian Ye , Chao Xu , Ying Zheng , Yining Xu , Yuluo Chen , Liangjie Chi , Jia Lin , Feng Li , Yao Lin , Qingshui Wang","doi":"10.1016/j.bbagen.2024.130739","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer remains a common malignancy with poor prognosis. While lactate metabolism is recognized as a significant factor in tumor progression, its potential as a predictive tool for treatment response remains unexplored. This study introduces a novel Lactate-Related Gene Signature (LRGS) designed to predict both survival outcomes and therapy responses in gastric cancer patients.</div></div><div><h3>Methods</h3><div>We comprehensively analyzed 335 lactate-related genes from 11 metabolic pathways using MSigDB, identifying 278 differentially expressed genes between gastric cancer and normal tissues. Employing the LASSO Cox regression model, we developed an innovative LRGS formula based on the expression of 16 key lactate-related genes. The impact of Solute Carrier Family 5 Member 12 (SLC5A12), a gene of particular interest, on gastric cancer cell functions was evaluated using in vitro assays and an in vivo zebrafish model.</div></div><div><h3>Results</h3><div>Our newly established LRGS demonstrated robust capability in stratifying gastric cancer patients by survival risk. Notably, the LRGS-low subtype showed significantly improved overall and disease-free survival rates compared to the LRGS-high subtype. A key finding was LRGS's ability to predict patient responses to both adjuvant chemotherapy and immunotherapy. Random forest analysis identified SLC5A12 as the most significant gene differentiating gastric cancer from normal tissues. Functional experiments confirmed SLC5A12's role in promoting gastric cancer cell proliferation, invasion, and migration both in vitro and in vivo.</div></div><div><h3>Conclusion</h3><div>The LRGS is a dependable and efficient prognostic tool for assessing the survival outcomes in individuals with gastric cancer, as well as a predictor of patient response to adjuvant chemotherapy and immunotherapy.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1869 2","pages":"Article 130739"},"PeriodicalIF":2.8000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochimica et biophysica acta. General subjects","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S030441652400182X","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Gastric cancer remains a common malignancy with poor prognosis. While lactate metabolism is recognized as a significant factor in tumor progression, its potential as a predictive tool for treatment response remains unexplored. This study introduces a novel Lactate-Related Gene Signature (LRGS) designed to predict both survival outcomes and therapy responses in gastric cancer patients.

Methods

We comprehensively analyzed 335 lactate-related genes from 11 metabolic pathways using MSigDB, identifying 278 differentially expressed genes between gastric cancer and normal tissues. Employing the LASSO Cox regression model, we developed an innovative LRGS formula based on the expression of 16 key lactate-related genes. The impact of Solute Carrier Family 5 Member 12 (SLC5A12), a gene of particular interest, on gastric cancer cell functions was evaluated using in vitro assays and an in vivo zebrafish model.

Results

Our newly established LRGS demonstrated robust capability in stratifying gastric cancer patients by survival risk. Notably, the LRGS-low subtype showed significantly improved overall and disease-free survival rates compared to the LRGS-high subtype. A key finding was LRGS's ability to predict patient responses to both adjuvant chemotherapy and immunotherapy. Random forest analysis identified SLC5A12 as the most significant gene differentiating gastric cancer from normal tissues. Functional experiments confirmed SLC5A12's role in promoting gastric cancer cell proliferation, invasion, and migration both in vitro and in vivo.

Conclusion

The LRGS is a dependable and efficient prognostic tool for assessing the survival outcomes in individuals with gastric cancer, as well as a predictor of patient response to adjuvant chemotherapy and immunotherapy.

查看原文本刊更多论文

评估乳酸代谢在胃癌预后评估和治疗反应预测中的作用，重点关注SLC5A12的致癌作用。

背景：胃癌是一种常见的恶性肿瘤，预后较差。虽然乳酸代谢被认为是肿瘤进展的重要因素，但其作为治疗反应预测工具的潜力仍未被探索。本研究介绍了一种新的乳酸相关基因标记（LRGS），旨在预测胃癌患者的生存结局和治疗反应。方法：利用MSigDB对11条代谢途径中的335个乳酸相关基因进行综合分析，鉴定出278个胃癌组织与正常组织差异表达基因。采用LASSO Cox回归模型，基于16个关键乳酸相关基因的表达，我们开发了一个创新的LRGS公式。通过体外实验和体内斑马鱼模型评估了溶质载体家族5成员12 （SLC5A12）对胃癌细胞功能的影响，这是一个特别感兴趣的基因。结果：我们新建立的LRGS在根据生存风险对胃癌患者进行分层方面显示出强大的能力。值得注意的是，与lrgs -高亚型相比，lrgs -低亚型的总体生存率和无病生存率显著提高。一个关键的发现是LRGS能够预测患者对辅助化疗和免疫治疗的反应。随机森林分析发现SLC5A12是区分胃癌与正常组织最显著的基因。体外和体内功能实验均证实了SLC5A12在促进胃癌细胞增殖、侵袭和迁移中的作用。结论：LRGS是评估胃癌患者生存结果的可靠和有效的预后工具，也是患者对辅助化疗和免疫治疗反应的预测指标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biochimica et biophysica acta. General subjects 生物-生化与分子生物学

CiteScore

6.40

自引率

0.00%

发文量

139

审稿时长

30 days

期刊介绍： BBA General Subjects accepts for submission either original, hypothesis-driven studies or reviews covering subjects in biochemistry and biophysics that are considered to have general interest for a wide audience. Manuscripts with interdisciplinary approaches are especially encouraged.