Low gamma-butyrobetaine dioxygenase (BBOX1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma: a machine learning approach

by Selleckchem | May 17 2023

Gamma-butyrobetaine dioxygenase (BBOX1) is a catalyst for the conversion of gamma-butyrobetaine to l-carnitine, which is detected in normal renal tubules. The purpose of this study was to analyze the prognosis, immune response, and genetic alterations associated with low BBOX1 expression in patients with clear cell renal cell carcinoma (RCC). We analyzed the relative influence of BBOX1 on survival using machine learning and investigated drugs that can inhibit renal cancer cells with low BBOX1 expression. We analyzed clinicopathologic factors, survival rates, immune profiles, and gene sets according to BBOX1 expression in a total of 857 patients with kidney cancer from the Hanyang University Hospital cohort (247 cases) and The Cancer Genome Atlas (610 cases). We employed immunohistochemical staining, gene set enrichment analysis, in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machines. BBOX1 expression in RCC was decreased compared with that in normal tissues. Low BBOX1 expression was associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils. In gene set enrichment analyses, low BBOX1 expression was related to gene sets with oncogenic activity and a weak immune response. In pathway network analysis, BBOX1 was linked to regulation of various T cells and programmed death-ligand 1. In vitro drug screening showed that midostaurin, BAY-61-3606, GSK690693, and linifanib inhibited the growth of RCC cells with low BBOX1 expression. Low BBOX1 expression in patients with RCC is related to short survival time and reduced CD8+ T cells; midostaurin, among other drugs, may have enhanced therapeutic effects in this context.

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This study investigated the impact of low BBOX1 expression in patients with clear cell renal cell carcinoma (RCC). The researchers analyzed various factors, including clinicopathologic features, survival rates, immune profiles, and genetic alterations associated with low BBOX1 expression in a cohort of 857 kidney cancer patients from Hanyang University Hospital and The Cancer Genome Atlas.

The study found that BBOX1 expression in RCC was decreased compared with normal tissues, and low BBOX1 expression was associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils. Gene set enrichment analyses revealed that low BBOX1 expression was related to gene sets with oncogenic activity and a weak immune response. Pathway network analysis demonstrated that BBOX1 was linked to regulation of various T cells and programmed death-ligand 1.

Moreover, the researchers used in vitro drug screening to identify drugs that could inhibit renal cancer cells with low BBOX1 expression. The study found that midostaurin, BAY-61-3606, GSK690693, and linifanib inhibited the growth of RCC cells with low BBOX1 expression.

Overall, the study suggests that low BBOX1 expression in patients with RCC is associated with short survival time and reduced CD8+ T cells. The findings also suggest that midostaurin, among other drugs, may have enhanced therapeutic effects in this context.