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author:

Lin, Chenyi (Lin, Chenyi.) [1] | Ye, Jianjian (Ye, Jianjian.) [2] | Xu, Chao (Xu, Chao.) [3] | Zheng, Ying (Zheng, Ying.) [4] | Xu, Yining (Xu, Yining.) [5] | Chen, Yuluo (Chen, Yuluo.) [6] | Chi, Liangjie (Chi, Liangjie.) [7] | Lin, Jia (Lin, Jia.) [8] | Li, Feng (Li, Feng.) [9] | Lin, Yao (Lin, Yao.) [10] | Wang, Qingshui (Wang, Qingshui.) [11]

Indexed by:

SCIE

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 lactaterelated 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.

Keyword:

Chemotherapy Gastric cancer Immunotherapy Lactate

Community:

  • [ 1 ] [Lin, Chenyi]Putian Hanjiang Hosp, Dept Gastroenterol, Putian 351100, Fujian, Peoples R China
  • [ 2 ] [Xu, Yining]Fujian Univ Tradit Chinese Med, Innovat & Transformat Ctr, Fujian Macao Sci & Technol Cooperat Base Tradit Ch, Fuzhou 350000, Fujian, Peoples R China
  • [ 3 ] [Lin, Jia]Fujian Univ Tradit Chinese Med, Innovat & Transformat Ctr, Fujian Macao Sci & Technol Cooperat Base Tradit Ch, Fuzhou 350000, Fujian, Peoples R China
  • [ 4 ] [Lin, Yao]Fujian Univ Tradit Chinese Med, Innovat & Transformat Ctr, Fujian Macao Sci & Technol Cooperat Base Tradit Ch, Fuzhou 350000, Fujian, Peoples R China
  • [ 5 ] [Wang, Qingshui]Fujian Univ Tradit Chinese Med, Innovat & Transformat Ctr, Fujian Macao Sci & Technol Cooperat Base Tradit Ch, Fuzhou 350000, Fujian, Peoples R China
  • [ 6 ] [Ye, Jianjian]Fujian Med Univ, Affiliated Nanping Hosp 1, Intervent Vasc Surg, Nanping 353000, Fujian, Peoples R China
  • [ 7 ] [Xu, Chao]Fujian Med Univ, Shengli Clin Med Coll, Dept Gastrointestinal Surg, Fuzhou 350000, Fujian, Peoples R China
  • [ 8 ] [Chi, Liangjie]Fujian Med Univ, Shengli Clin Med Coll, Dept Gastrointestinal Surg, Fuzhou 350000, Fujian, Peoples R China
  • [ 9 ] [Xu, Chao]Fuzhou Univ Affiliated Prov Hosp, Fujian Prov Hosp, Fuzhou 350000, Fujian, Peoples R China
  • [ 10 ] [Chi, Liangjie]Fuzhou Univ Affiliated Prov Hosp, Fujian Prov Hosp, Fuzhou 350000, Fujian, Peoples R China
  • [ 11 ] [Li, Feng]Fuzhou Univ Affiliated Prov Hosp, Fujian Prov Hosp, Fuzhou 350000, Fujian, Peoples R China
  • [ 12 ] [Zheng, Ying]Fuzhou Second Hosp, Dept Obstet, Fuzhou 350000, Fujian, Peoples R China
  • [ 13 ] [Chen, Yuluo]Fujian Normal Univ, Fuzhou 350000, Fujian, Peoples R China
  • [ 14 ] [Li, Feng]Fujian Med Univ, Shengli Clin Med Coll, Dept Pathol, Fuzhou 350000, Fujian, Peoples R China

Reprint 's Address:

  • 池良杰 李峰

    [Lin, Jia]Fujian Univ Tradit Chinese Med, Innovat & Transformat Ctr, Fujian Macao Sci & Technol Cooperat Base Tradit Ch, Fuzhou 350000, Fujian, Peoples R China;;[Lin, Yao]Fujian Univ Tradit Chinese Med, Innovat & Transformat Ctr, Fujian Macao Sci & Technol Cooperat Base Tradit Ch, Fuzhou 350000, Fujian, Peoples R China;;[Wang, Qingshui]Fujian Univ Tradit Chinese Med, Innovat & Transformat Ctr, Fujian Macao Sci & Technol Cooperat Base Tradit Ch, Fuzhou 350000, Fujian, Peoples R China;;[Chi, Liangjie]Fujian Med Univ, Shengli Clin Med Coll, Dept Gastrointestinal Surg, Fuzhou 350000, Fujian, Peoples R China;;[Chi, Liangjie]Fuzhou Univ Affiliated Prov Hosp, Fujian Prov Hosp, Fuzhou 350000, Fujian, Peoples R China;;[Li, Feng]Fuzhou Univ Affiliated Prov Hosp, Fujian Prov Hosp, Fuzhou 350000, Fujian, Peoples R China;;[Li, Feng]Fujian Med Univ, Shengli Clin Med Coll, Dept Pathol, Fuzhou 350000, Fujian, Peoples R China

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Source :

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS

ISSN: 0304-4165

Year: 2025

Issue: 2

Volume: 1869

2 . 8 0 0

JCR@2023

CAS Journal Grade:3

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 6

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