Development and external validation of an 18-gene tertiary lymphoid structure-related prognostic signature in gastric cancer
Year: 2026
Type: article
Abstract: Background: Tertiary lymphoid structures (TLS) contribute to local antitumor immunity, but TLS-related transcriptional signals do not directly measure histological TLS abundance or maturation. This study aimed to develop and externally evaluate a biologically constrained TLS-related gene (TLSRG) signature for prognostic stratification in gastric cancer and characterize its associated immune-stromal programmes. Methods: Transcriptomic and clinical data from 350 patients in The Cancer Genome Atlas stomach adenocarcinoma (TCGA-STAD) cohort and 431 patients in GSE84437 were used for development and external evaluation, respectively. Least absolute shrinkage and selection operator (LASSO)-Cox regression was applied to a predefined 39-gene panel. Overall survival (OS) was assessed using Kaplan-Meier analysis, Cox regression, the concordance index (C-index), and time-specific receiver operating characteristic (ROC) analysis. Additional analyses evaluated TLS-related cell-state and functional transcriptional surrogates, model-gene-overlap-excluded scores, cross-cohort association networks, 18-gene co-expression, and area under the curve (AUC) uncertainty using 2,000 patient-level bootstrap resamples. A combined clinical model underwent internal cross-validation using the precomputed risk score. Results: 0.617 for clinical variables alone. Conclusions: The TLSRG signature was associated with survival and reproducible stromal/angiogenic transcriptional features, although external discrimination was modest. Prospective spatial and functional studies are needed to determine its relationship with TLS maturation and clinical utility.
Source: Translational Cancer Research
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223364497