Expression of the checkpoint kinase BUB1 is a predictor of response to cancer therapies

Sep 21, 2026

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The study assesses BUB1 as a clinically relevant biomarker across cancers and in the context of drug response. A pan-cancer analysis shows BUB1 overexpression is common, especially in aggressive molecular subtypes, and correlates with staging, tumor size, invasion, hypoxia, and stemness. Prognostic impact varies with treatment in TCGA cohorts, indicating expression-level dependent sensitivity or resistance. Integrated in vitro drug sensitivity data identify candidate compounds with differential responses, while GO enrichment links BUB1-driven effects to mitosis and chromosome segregation.

LanguageEnglish

CategoryHealthcare

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Expression of the checkpoint kinase BUB1 is a predictor of response to cancer therapies

Pan-cancer biomarker analysis and clinical correlations

Prognostic value across TCGA treatment cohorts

Drug sensitivity integration and candidate compounds

Biological mechanisms via gene ontology enrichment

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Expression of the checkpoint kinase BUB1 is a predictor of response to cancer therapies Ylenia Cicirò1, Denise Ragusa2* & Arturo Sala1* The identification of clinically-relevant biomarkers is of upmost importance for the management of cancer, from diagnosis to treatment choices. We performed a pan-cancer analysis of the mitotic checkpoint budding uninhibited by benzimidazole 1 gene BUB1, in the attempt to ascertain its diagnostic and prognostic values, specifically in the context of drug response. BUB1 was found to be overexpressed in the majority of cancers, and particularly elevated in clinically aggressive molecular subtypes. Its expression was correlated with clinico-phenotypic features, notably tumour staging, size, invasion, hypoxia, and stemness. In terms of prognostic value, the expression of BUB1 bore differential clinical outcomes depending on the treatment administered in TCGA cancer cohorts, suggesting sensitivity or resistance, depending on the expression levels. We also integrated in vitro drug sensitivity data from public projects based on correlation between drug efficacy and BUB1 expression to produce a list of candidate compounds with differential responses according to BUB1 levels. Gene Ontology enrichment analyses revealed that BUB1 overexpression in cancer is associated with biological processes related to mitosis and chromosome segregation machinery, reflecting the mechanisms of action of drugs with a differential effect based on BUB1 expression. Despite significant improvements in clinical management of human cancers over the years, conventional therapeutic strategies alone have failed to achieve cures. According to latest statistics, cancer diagnoses have increased by 54.9% from 20201–3, suggesting that more accurate biological markers should be identified and used in the clinic for efficient diagnostic and prognostic evaluations. Pan-cancer analyses of large clinical datasets focusing on gene expression represent a promising strategy for the identification of clinical biomarkers4–6. Different stages ofthe cell cycle are tightly regulated by gateway control mechanisms known as checkpoints7, which are of particular interest in cancer due to its highly proliferative nature8. Mitotic checkpoint kinases have gained interest as therapeutic strategies in cancer, with the goal of lethal disruption of the mitotic machinery9. Among these, BUB1 is a highly conserved serine/threonine protein kinase involved in the mitotic checkpoint10. The main function of BUB1 is to organise the spindle assembly checkpoint (SAC) during mitosis, monitoring chromosome segregation and stable attachment of the spindle-microtubule polymers to kinetochores11, 12. The SAC is composed of different proteins, such as BUB1, BUB3, MAD1, MAD2, and MAD3 (BUBR1 in higher eukaryotes), AURKB, and CDC2011–14. BUB1 recruits several proteins to support chromosome alignment, and its knockout in mouse models results in embryonic lethality, suggesting that it is necessary for faithful mitosis12, 15, 16. Alterations in BUB1, including deletions, point mutations, and expression changes have been observed in several malignancies17–23. However, due to the various biological roles of BUB1 in the cell, it is not clear how BUB1 promotes or supports tumourigenesis. Although the mechanisms of action are not fully understood and still controversial, different studies correlated BUB1 expression (and limitedly BUB1 mutations) with poor prognosis in several cancers, including breast cancer, glioma, prostate cancer, and salivary gland tumours24–28. Therefore, BUB1 expression might serve as a biomarker in cancer, although comprehensive analyses of BUB1 across malignancies are lacking. Therapeutic harnessing of SAC components has been of interest in pre-clinical and clinical settings, aiming to develop increasingly effective and limitedly toxic options, such as inhibitors ofAURKB

FAQs

What does the study evaluate regarding BUB1 in cancer?

It evaluates whether the checkpoint kinase BUB1 can act as a diagnostic/prognostic biomarker and whether BUB1 expression predicts response to cancer therapies.

Which clinical features are associated with BUB1 expression?

BUB1 expression correlates with tumor staging, size, invasion, hypoxia, and stemness.

How is BUB1 linked to differences in drug response?

By integrating drug sensitivity data, the study identifies candidate compounds showing differential responses according to BUB1 expression levels, and TCGA outcomes vary by treatment type.

Sep 21, 2026

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