Development and internal validation of a six-gene prognostic model based on galactose metabolism for overall survival in lung adenocarcinoma.

IF 2.1 4区医学 Q4 ONCOLOGY

Translational cancer research Pub Date : 2026-08-31 Epub Date: 2026-08-27 DOI:10.21037/tcr-2026-0696

Feng Zhang, Jian Fu, Xuxu Cui, Xutong Gao, Yanxia Kang

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引用次数: 0

Abstract

Background: Lung cancer remains a leading cause of cancer incidence and mortality globally. Metabolic reprogramming promotes tumor progression and shapes an immunosuppressive tumor microenvironment. Galactose metabolism is involved in multiple malignancies, but its prognostic value in lung adenocarcinoma (LUAD) remains unclear. This study aimed to develop and internally validate a galactose metabolism-related multigene prognostic model for LUAD.

Methods: A retrospective prognostic model development and internal validation study was performed using RNA sequencing (RNA-seq) and clinical data from 585 LUAD patients in The Cancer Genome Atlas (TCGA). Differential expression, functional enrichment, univariate and multivariate Cox regression were applied to construct a prognostic gene signature. Internal validation was performed using bootstrap resampling. Model performance was evaluated by time-dependent receiver operating characteristic (ROC), C-index, calibration, and Kaplan-Meier analysis. Associations between the model and immune infiltration, immunotherapy responsiveness, and tumor stemness were also analyzed.

Results: A six-gene prognostic model (GALT, GANC, PGM1, GALM, B4GALT1, PGM2) was developed. The model showed good discrimination with 1-, 3-, and 5-year area under the curve (AUC) values of 0.719, 0.693, and 0.684, respectively. The low-risk group exhibited significantly longer survival, increased antitumor immune infiltration (CD8+ T cells, M1 macrophages, activated CD4+ memory T cells), higher expression of T cell proliferation-related genes, lower immune checkpoint expression, better predicted immunotherapy response, and lower tumor stemness compared with the high-risk group.

Conclusions: We developed and internally validated a six-gene prognostic model for LUAD based on galactose metabolism. The model shows moderate prognostic performance and is associated with antitumor immunity and tumor stemness. It may be used for prognostic risk stratification and to guide personalized immunotherapy in LUAD.

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基于半乳糖代谢的肺腺癌总生存的六基因预后模型的开发和内部验证。

背景：肺癌仍然是全球癌症发病率和死亡率的主要原因。代谢重编程促进肿瘤进展并形成免疫抑制肿瘤微环境。半乳糖代谢与多种恶性肿瘤有关，但其在肺腺癌（LUAD）中的预后价值尚不清楚。本研究旨在建立并内部验证半乳糖代谢相关的LUAD多基因预后模型。方法：利用癌症基因组图谱（TCGA）中585例LUAD患者的RNA测序（RNA-seq）和临床数据，进行回顾性预后模型开发和内部验证研究。差异表达、功能富集、单变量和多变量Cox回归应用于构建预后基因标记。内部验证使用自举重采样进行。采用随时间变化的受试者工作特征（ROC）、c指数、校准和Kaplan-Meier分析来评估模型的性能。我们还分析了模型与免疫浸润、免疫治疗反应性和肿瘤干性之间的关系。结果：建立了GALT、GANC、PGM1、GALM、B4GALT1、PGM2六基因预后模型。该模型的1年、3年和5年曲线下面积（AUC）分别为0.719、0.693和0.684，具有较好的判别性。与高危组相比，低危组患者的生存期明显延长，抗肿瘤免疫浸润（CD8+ T细胞、M1巨噬细胞、活化CD4+记忆T细胞）增加，T细胞增殖相关基因表达增加，免疫检查点表达降低，免疫治疗反应预测更好，肿瘤干性更低。结论：我们开发并内部验证了基于半乳糖代谢的六基因LUAD预后模型。该模型表现出中等的预后表现，并与抗肿瘤免疫和肿瘤干性有关。它可以用于预后风险分层和指导LUAD的个性化免疫治疗。

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来源期刊

Translational cancer research ONCOLOGY-

CiteScore

2.10

自引率

0.00%

发文量

252

期刊介绍： Translational Cancer Research (Transl Cancer Res TCR; Print ISSN: 2218-676X; Online ISSN 2219-6803; http://tcr.amegroups.com/) is an Open Access, peer-reviewed journal, indexed in Science Citation Index Expanded (SCIE). TCR publishes laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer; results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of cancer patients. The focus of TCR is original, peer-reviewed, science-based research that successfully advances clinical medicine toward the goal of improving patients'' quality of life. The editors and an international advisory group of scientists and clinician-scientists as well as other experts will hold TCR articles to the high-quality standards. We accept Original Articles as well as Review Articles, Editorials and Brief Articles.