Combination of tumor mutation burden and immune infiltrates for the prognosis of lung adenocarcinoma.

ABSTRACT

BACKGROUND: Tumor mutation burden (TMB) levels are associated with immune infiltrates in the tumor microenvironment and can modulate the responses to immune checkpoint inhibitors (ICIs) in lung adenocarcinoma (LUAD) patients. This study aimed at exploring the potential role of a signature of genes associated with TMB and immune infiltrates and the relevant nomogram in the prognosis of LUAD. MATERIALS AND METHODS: The TMB levels in LUAD patients in the Cancer Genome Atlas (TCGA) were analyzed. The differentially expressed genes (DEGs) between the higher- and lower-TMB subgroups were functionally analyzed. The immune-related DEGs and their relationship with immune infiltrates in the tumor environment between two subgroups were analyzed. Nine immune-related DEGs were used to generate a TMB-related immune signature. The sensitivity to immunotherapy in TCGA-LUAD patients was analyzed by immunophenotypic scores (IPS). Subsequently, a nomogram was generated using tumor-related parameters and the signature score. The signature or nomogram values in predicting overall survival (OS) were evaluated and validated in LUAD patients in the GSE30219 and GSE72094. RESULT: There were 468 DEGs between the higher and lower-TMB subgroups of LUAD patients. The TMB levels were associated positively with the number of immune infiltrates in LUAD patients. Nine DEGs were related to immune infiltrates in the tumor environment. The higher signature scores (high-risk) were associated with poor prognosis of LUAD in the TCGA, which was validated in LUAD patients of the GSE30219 and GSE72094 datasets. Interestingly, the patients in the high-risk group had higher PD-L1 expression in their tumors and the risk scores in LUAD patients. The IPS of LUAD patients in the high-risk group were predicted to benefit from immunotherapy. Finally, the nomogram had high AUC values in predicting the OS of LUAD patients. CONCLUSION: The TMB-related immune signature or nomogram is valuable for the prognosis of LUAD patients and evaluating their responses to ICIs. These relevant genes may participate into the pathogenesis, ICIs, and drug resistance of LUAD.