In this study, we constructed an eight-gene metabolic related signature for LUAD. The eight-gene prognostic signature (including PLAUR, F2, UGT2B17, GNG7, IDO2, ST3GAL6, PIK3CG, and GLS2) exhibited a good prognostic value in the TCGA LUAD training dataset and testing dataset. In addition, the risk score based on the signature model was significantly correlated with immune cell infiltration and expression levels of immune markers in LUAD patients. LUAD cohorts from GEO were used to validate the model, indicating the usefulness of the model. In summary, we developed and validated an eight-gene signature model for LUAD, which can reflect the immune microenvironment characteristics and predict the prognostic outcomes for LUAD patients.

Background Lung adenocarcinoma (LUAD) is the most prevalent non-small cell lung cancer (NSCLC). Patients with LUAD have a poor 5-year survival rate. The use of immune checkpoint inhibitors (ICIs) for the treatment of LUAD has been on the rise in the past decade. This study explored the prognostic role of butyrophilin-like 9 (BTNL9) in LUAD. Methods Gene expression profile of buytrophilins (BTNs) was determined using the GEPIA database. The effect of BTNL9 on the survival of LUAD patients was assessed using Kaplan-Meier plotter and OncoLnc. Correlation between BTNL9 expression and tumor-infiltrating immune cells (TILs) was explored using TIMER and GEPIA databases. Further, the relationship between BTNL9 expression and drug response was evaluated using CARE. Besides, construction and evaluation of nomogram based on BTNL9 expression and TNM stage. Results BTNL9 expression was downregulated in LUAD and was associated with a poor probability of 1, 3, 5-years overall survival (OS). In addition, BTNL9 expression was regulated at epigenetic and post-transcriptional modification levels. Moreover, BTNL9 expression was significantly positively correlated with ImmuneScore and ESTIMATEScore. Furthermore, BTNL9 expression was positively associated with infiltration levels of B cells, CD4+ T cells, and macrophages. Kaplan-Meier analysis showed that BTNL9 expression in B cells and dendritic cells (DCs) was significantly associated with OS. BTNL9 expression was significantly positively correlated with CARE scores. Conclusions These findings show that BTNL9 is a potential prognostic biomarker for LUAD. Low BTNL9 expression levels associated with low infiltration levels of naïve B cells, and DCs in the tumor microenvironment are unfavorable for OS in LUAD patients.

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.

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.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.

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