Co-stimulatory molecule clusters correlate with survival, immune infiltration, and tumor mutation burden in non-small cell lung cancer

Abstract

We aimed to identify co-stimulatory molecule clusters and explore their associations with immune infiltration and tumor mutation burden (TMB) in non-small cell lung cancer (NSCLC), using a systematic analysis based on RNA-seq and mutation data in TCGA database. Twelve immune-related prognostic co-stimulatory molecules were screened. Based on the expression of these molecules, all samples were divided into four clusters by Consensus clustering analysis. Clusters 2 and 4 were associated with worse survival and favorable prognosis, respectively. The proportion of patients with different age, Pathologic T and Pathologic stage among these four clusters showed significant differences. Cluster 4 was associated with a higher proportion of patients with pathological N0 and T1–2, as well as early tumors (stages I–II). Additionally, these clusters significantly differed in terms of immune infiltration of memory B cells, regulatory T cells, M2 macrophages, and activated memory CD4+ T cells, as well as the expression of six checkpoint genes. Worse survival was associated with a high rather than a low TMB; among the clusters, clusters 4 and 2 had the lowest and highest TMB, respectively. In conclusion, four co-stimulatory molecule clusters identified in NSCLC significantly differed in terms of survival, tumor stage, immune response, and TMB. Highlights Four co-stimulatory molecule clusters were identified that correlated differently with survival. Feature genes of four clusters were enriched in different functions. Four clusters significantly differed in terms of tumor stage, immune infiltration, and checkpoint gene expression. Worse survival was associated with high, compared with low TMB. Survival was better for cluster 4 than other clusters, and TMB was low.

Keywords

• non-small cell lung cancer
• co-stimulatory molecules
• immune
• molecular clusters
• tumor mutation burden