IGSF6 is a biomarker associated with anti-tumor immune response in lung adenocarcinoma

Abstract

Background: Immunoglobulin superfamily 6 (IGSF6) is a novel member of the immunoglobulin superfamily, and it is related to multiple diseases. However, the association of IGSF6 with the prognosis and anti-tumor immune response in lung adenocarcinoma (LUAD) remains unknown. Results: By analyzing IGSF6 expression in different cancers based on the pan-cancer data from The Cancer Genome Atlas (TCGA), it was found that IGSF6 expression was decreased in LUAD. Results of quantitative-real-time-PCR (qRT-PCR), western-blot and immunohistochemistry (IHC) staining further confirmed this finding in paired tumor and normal tissues of LUAD patients. Meanwhile, promoter methylation level of IGSF6in LUAD samples increased compared to that in peritumor samples, implying a potential mechanism that leads to the aberrant expression of IGSF6 in LUAD. By estimating the correlation between IGSF6 expression and the prognosis of LUAD, we found that low IGSF6 expression was significantly related to a worse survival rate. The enrichment analysis of IGSF6 co-expression showed that IGSF6 expression was closely associated with gene sets involved in immune cell proliferation and exogenous antigen presentation. In addition, high IGSF6 expression was positively correlated with immune infiltrates with anti-tumor activity, including M1 macropahges, dendritic cells (DCs), and T helper 1 (Th1) cells. Finally, IGSF6 protein was indicated to be mainly located on the membrane of macrophages in LUAD, which might enable exogenous antigen uptake and presentation so as to regulate anti-tumor immune response. Conclusions:IGSF6 is a biomarker for LUAD, which may promote the anti-tumor immune response leading to ameliorative prognosis.