BUB1B is a novel prognostic-related biomarker and correlated with immune infiltrates in lung adenocarcinoma.

BACKGROUND

The BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B), one of the core proteins of the spindle checkpoint, has been linked to a poor prognosis in many tumors. Our purpose was to explore the clinical value and biological function of BUB1B in lung adenocarcinoma (LUAD).

METHODS

TCGA Level 3 RSEM-normalized RNA-seq data, GTEx standardized expression data, TIMER (for purity-corrected immune infiltration estimation), and single-sample gene set enrichment analysis (ssGSEA) (using the GSVA R package with method = "ssgsea") were used to analyze BUB1B expression, prognosis, immune infiltration in LUAD. The role of BUB1B in H1650 and A549 cells was investigated through knocking-down BUB1B or overexpression BUB1B.

RESULTS

BUB1B expression was significantly increased in LUAD tissues. High levels of BUB1B indicated a worse outcome. BUB1B expression was closely linked to tumor size and TMN stage, which was an independent risk factor for the prognosis of LUAD. BUB1B was associated with 20 types of TIICs as determined by ssGSEA analysis of 28 immune cell signatures. In TIMER database, BUB1B showed a positive correlation with neutrophil infiltration, but negatively correlated with immune infiltration levels of B cells and CD4 + T cells. These findings were cross-validated across TIMER, ssGSEA, and GEPIA platforms. Low dendritic cell infiltration, low B cell infiltration, and high expression of BUB1B were closely linked to lower cumulative survival in patients with LUAD. BUB1B overexpression augmented the proliferation, invasion and migration of A549 and H1650 cells, reduced the apoptosis, and promoted the EMT process. Whereas, BUB1B knockdown showed the opposite results. Additionally, BUB1B overexpression promoted macrophage recruitment by regulating CCL2 and p-P65 expression, as confirmed by in vitro Transwell chemotaxis assays using THP-1-derived macrophages.

CONCLUSIONS

BUB1B may be a critical factor in regulating immune function and may serve as a novel clinical prognostic marker of LUAD patients.