Low expression of BTN3A3 indicates poor prognosis and promotes cell proliferation, migration and invasion in non-small cell lung cancer

BACKGROUND: The butyrophilin (BTN) family has many members with diverse functions related to immunomodulation, initiation and progression of tumors. BTN3A3 belongs to the BTN family, and exploring its expression and correlation with the prognosis of non-small cell lung cancer (NSCLC) patients has great clinical significance. METHODS: Clinical specimens were used to detect BTN3A3 expression. Small interfering RNA (siRNA) was used to knock down BTN3A3 and analyze the proliferative, migratory and invading ability of the transfected NSCLC cells. Multiplex immunofluorescence staining was used to detect the expression of BTN3A3 protein in the tumor microenvironment (TME). We analyzed the relationship between the expression of BTN3A3 and the clinicopathological features and prognosis of NSCLC patients. RESULTS: The expression of BTN3A3 in NSCLC tissues was significantly lower than in adjacent tissues, and patients with low expression of BTN3A3 had late clinical stages and lower degree of tumor differentiation. Knocking down BTN3A3 promoted the proliferation, migration and invasion of NSCLC. In the TME, the density of BTN3A3+ tumor cells positively correlated with the density of CD8+ T cells, and the patients with low expression of BTN3A3 had poor overall survival (OS). CONCLUSIONS: Changes in the BTN3A3 expression level may play a potential key role in the carcinogenesis and development of NSCLC. Patients with low expression of BTN3A3 showed a more aggressive and invasive phenotype and a lower level of CD8+ T-cell infiltration, which may be an important factor affecting the OS of NSCLC patients.