Butyrophilin-like 9 regulates immune infiltration and serves as a prognostic marker in lung adenocarcinoma

Abstract

Background: Butyrophilin (BTN) and butyrophilin-like (BTLN) belong to immunoglobulin superfamily, and also pertain the B7 co-stimulatory molecules family, which has multiple roles in immune modulation. Whether the BTNL9 expression in lung adenocarcinoma (LUAD) correlates with outcome has not been evaluated.Materials and methods: Oncomine and GEPIA were used to analyze the BTNL9, while its mRNA expression in LUAD and corresponding adjacent tissues was investigated using TIMER. The clinical prognosis of BTNL9 was assessed in the GEPIA, Kaplan-Meier plotter, and OncoLnc. Besides, the correlation between BTNL9 and tumor-infiltrating immune cells (TILs) was analyzed using TIMER and GEPIA. The correlation between BTNL9 expression and drug response was analyzed using CARE.Results: BNL9 expression was significantly low in LUAD. Low BTNL9 expression was associated with poor OS, and its expression was found to be regulated by both epigenetic regulation and post-transcriptional modification. BTNL9 expression was significant positively correlated with ImmuneScore and ESTIMATEScore. Moreover, BTNL9 expression was positively correlated with infiltrating levels of B cells, CD4+T, and macrophages, but Kaplan-Meier analysis showed that BTNL9 expression in B cells and DCs was significantly associated with OS. Furthermore, BTNL9 expression has significant positive CARE scores. Conclusions: Low BTNL9 expression can prevent the infiltration of naïve B cells and DCs in the tumor microenvironment and worsen the outcome in LUAD patients. Besides, these findings also suggest the potential role of BTNL9 as a prognostic biomarker and a new immuno-target.