文献类型：期刊文献

英文题名：Transcriptome-Based Six-Gene Fatty Acid Metabolism Signature for Prognosis and Predicted Immunotherapy Response in Lung Adenocarcinoma: Cross-Population Validation

作者：Ma, Qiangping[1];Liang, Jianqing[1,2,3];Li, Jintian[1,2];Li, Juan[3]

第一作者：Ma, Qiangping

通信作者：Liang, JQ[1];Liang, JQ[2];Liang, JQ[3]

机构：[1]Gansu Univ Chinese Med, Sch Clin Med Tradit Chinese Med, Lanzhou 730101, Peoples R China;[2]Minist Educ, Key Lab Dunhuang Med & Transformat, Lanzhou 730000, Peoples R China;[3]Gansu Univ Chinese Med, Sch Basic Med Sci, Lanzhou 730101, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Sch Clin Med Tradit Chinese Med, Lanzhou 730101, Peoples R China;[2]corresponding author), Minist Educ, Key Lab Dunhuang Med & Transformat, Lanzhou 730000, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Sch Basic Med Sci, Lanzhou 730101, Peoples R China.|[107351d2d02a88e1f325f]甘肃中医药大学基础医学院（敦煌医学研究所）;[10735]甘肃中医药大学;

年份：2026

卷号：17

期号：8

外文期刊名：GENES

收录：;Scopus(收录号：2-s2.0-105048421699);WOS:【SCI-EXPANDED(收录号:WOS:001859755700001)】；

基金：This research was funded by the National Natural Science Foundation of China (82560964); the Open Project of the Key Laboratory of Dunhuang Medicine and Transformation, Ministry of Education (DHYX24-01); and the 2024 'Qihuang Talents' Mentor Special Fund (Doctoral Supervisor Project) for the First-Level Discipline of Traditional Chinese Medicine (ZYXKBD-202418).

语种：英文

外文关键词：lung adenocarcinoma; fatty acid metabolism; elastic net; prognostic signature; immune infiltration; immunotherapy response

摘要：Objectives: Lung adenocarcinoma (LUAD) is molecularly heterogeneous, and the prognostic relevance of fatty acid metabolism (FAM) remains incompletely defined. We aimed to develop a concise FAM-associated prognostic signature and examine its associations with the immune microenvironment and candidate therapeutic vulnerabilities. Methods: TCGA-LUAD transcriptomic and survival data were integrated with MSigDB FAM gene sets. Univariate Cox and elastic-net Cox regression were used to derive a risk score. The locked formula was evaluated in a Japanese cohort (GSE31210) and a U.S. cohort (GSE72094). Immune-infiltration algorithms as well as TIDE, GDSC2, and CPTAC data were used for exploratory immune, drug sensitivity, and protein-level analyses. Results: The six-gene signature comprised CYP4B1, ACOXL, DPEP2, HPGDS, CA4, and ALOX15. High-risk patients had shorter overall survival in the TCGA and both external cohorts (GSE31210, log-rank p = 0.0039; GSE72094, p < 0.0001). The risk score remained independently prognostic after adjustment for age, sex, and clinical stage. High-risk tumours showed lower immune and stromal signals, greater immune exclusion, and a lower TIDE-predicted ICB response proportion. GDSC2 analyses and expression comparisons identified associations with predicted drug sensitivity and lipogenic target expression. Five detectable signature proteins were less abundant in tumours in CPTAC data. Conclusions: This signature stratified patients by prognosis in two geographically distinct external cohorts and generated testable metabolic and immune hypotheses. Prospective validation, assay standardisation, and functional studies are required before clinical use.