Comprehensive analysis of tertiary lymphoid structures-related genes for prognostic prediction, molecular subtypes and immune infiltration in gastric cancer.

Abstract

Gastric cancer (GC) is a highly heterogeneous malignancy and survival rates of advanced GC patients are unsatisfactory. Tertiary lymphoid structures (TLS) are recently identified as lymphoid-like structures that are directly related to tumor prognosis and immune response. However, the association of tertiary lymphoid structures-related genes (TLS-RGs) with prognosis and immune response in GC remains unclear. In our study, a comprehensive analysis of the role of TLS-RGs in GC was performed based on public data, and the difference of TLS-RGs expression, TLS-RGs mutation frequency, pathway enrichment, differentially expressed gene, immune landscape, immunotherapy and drug sensitivity was analyzed. We found that TLS-RGs were altered in GC in terms of expression and mutation. The difference of survival, immune landscape and enrichment pathway exists between TLS clusters. Immune checkpoint differences were also evident between gene clusters. The grouping by TLS score indicated that patients in the low TLS score group had a better prognosis and a lower degree of immune escape. For immunotherapy, the low TLS score group showed better outcomes than the high TLS score group. Sensitivity to chemotherapeutic agents differed between TLS score groups. In conclusion, we comprehensively analyzed the role of TLS-RGs in GC, constructed nomogram that can accurately predict the prognosis of GC patients, and the TLS score can reflect the immune landscape of patients, providing the possibility of personalized design of immunotherapy and targeted drug therapy for GC patients.