Correlation of Tryptophan Metabolic Pathway with Immune Activation and Chemosensitivity in Patients with Lung Adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is the most common type of lung cancer with high malignancy and easy metastasis in the early stage. In this study, we aimed to figure out the role of tryptophan metabolic pathway in LUAD prognosis and treatment. Different molecular subtypes were constructed based on tryptophan metabolism-related genes. Significant prognostic genes and clinical prognostic characteristics, immune infiltration level, and pathway activity in different subtypes were determined by algorithms, such as the least absolute shrinkage and selection operator (Lasso), CIBERSORT, Tumor Immune Dysfunction and Exclusion (TIDE), and gene set enrichment analysis (GSEA). The effect of different gene mutation types on the prognosis of patients with LUAD was explored. The clinical prognosis model was constructed and its reliability was verified. Of the 40 genes in the tryptophan metabolism pathway, 13 had significant prognostic significance. Based on these 13 genes, three molecular subtypes (C1, C2, and C3) were established. Among them, C1 had the worst prognosis and the lowest enrichment score of tryptophan metabolism. At the same time, C1 had the most genetic variation, the highest level of immune infiltration, and significantly activated pathways related to tumor development. The high-risk and low-risk groups had significant differences in prognosis, immune infiltration and pathway enrichment, which was consistent with the results of subtype analysis. Mutation in tryptophan metabolism-related genes leads to abnormal tryptophan metabolism, immune deficiency, and activation of cancer-promoting pathways. This results in high malignancy, poor prognosis, and failure of traditional clinical treatments. Through the establishment of risk score (RS) clinical prognosis model, we determined that RS could reliably predict the prognosis of patients with LUAD.