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Prognostic Value of BUB1 for Predicting Non-Muscle-Invasive Bladder Cancer Progression.

ABSTRACT: Non-muscle-invasive bladder cancer (NMIBC) is a common disease with a high recurrence rate requiring lifetime surveillance. Although NMIBC is not life-threatening, it can progress to muscle-invasive bladder cancer (MIBC), a lethal form of the disease. The management of the two diseases differs, and patients with MIBC require aggressive treatments such as chemotherapy and radical cystectomy. NMIBC patients at a high risk of progression benefit from early immediate cystectomy. Thus, identifying concordant markers for accurate risk stratification is critical to predict the prognosis of NMIBC. Candidate genetic biomarkers associated with NMIBC prognosis were screened by RNA-sequencing of 24 tissue samples, including 16 NMIBC and eight normal controls, and by microarray analysis (GSE13507). Lastly, we selected and investigated a mitotic checkpoint serine/threonine kinase, BUB1, that regulates chromosome segregation during the cell cycle. BUB1 gene expression was tested in 86 NMIBC samples and 15 controls by real-time qPCR. The performance of BUB1 as a prognostic biomarker for NMIBC was validated in the internal Chungbuk cohort (GSE13507) and the external UROMOL cohort (E-MTAB-4321). BUB1 expression was higher in NMIBC patients than in normal controls (p < 0.05), and the overexpression of BUB1 was correlated with NMIBC progression (log-rank test, p = 0.007). In in vitro analyses, BUB1 promoted the proliferation of bladder cancer cells by accelerating the G2/M transition of the cell cycle. Conclusively, BUB1 modulates the G2/M transition to promote the proliferation of bladder cancer cells, suggesting that it could serve as a prognostic marker in NMIBC.

SUBMITTER: Piao XM

PROVIDER: S-EPMC8657483 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Prognostic Value of BUB1 for Predicting Non-Muscle-Invasive Bladder Cancer Progression.

Piao Xuan-Mei XM You Chaelin C Byun Young Joon YJ Kang Ho Won HW Noh Junho J Lee Jaehyun J Lee Hee Youn HY Kim Kyeong K Kim Won Tae WT Yun Seok Joong SJ Lee Sang-Cheol SC Kang Kyuho K Kim Yong-June YJ

International journal of molecular sciences 20211125 23

Non-muscle-invasive bladder cancer (NMIBC) is a common disease with a high recurrence rate requiring lifetime surveillance. Although NMIBC is not life-threatening, it can progress to muscle-invasive bladder cancer (MIBC), a lethal form of the disease. The management of the two diseases differs, and patients with MIBC require aggressive treatments such as chemotherapy and radical cystectomy. NMIBC patients at a high risk of progression benefit from early immediate cystectomy. Thus, identifying co ...[more]

PMID: 34884561

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Project description:PurposeTo investigate the prognostic value of preoperative serum albumin to globulin ratio (AGR) in patients with non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of bladder tumor (TURB) with or without intravesical therapy (IVT).Materials and methodsWe retrospectively reviewed 1,096 consecutive patients with NMIBC. Levels of albumin and globulin were obtained before TURB and used to calculate the preoperative AGR level. Multivariable Cox regression analyses were performed to assess the prognostic effect of preoperative AGR on oncologic outcomes. Subgroup analyses were performed in patients based on the European Association of Urology (EAU) risk groups for NMIBC.ResultsLow AGR levels were observed in 389 (35.5%) patients. The median follow-up was 63.7 months (IQR 25.3-111). On multivariable Cox regression analysis, low AGR was associated with increased risk of progression to muscle-invasive BCa (MIBC) (HR 1.81, 95% CI 1.22-2.68, P = 0.003). The addition of AGR only minimally improved the discrimination ability of a base model that included established clinicopathologic features (C-index = 0.7354 vs. C-index = 0.7162). Low preoperative AGR was not significantly associated with the risk of disease recurrence (P = 0.31). In subgroup analyses based on patients' EAU risk groups, low preoperative AGR was not associated with recurrence-free survival (RFS) (P = 0.59) or progression-free survival (PFS) (P = 0.22) in any of the risk groups. Additionally, in patients treated with Bacillus Calmette-Guerin (BCG) for intermediate- or high-risk NMIBC, low AGR failed to predict disease recurrence or progression.ConclusionPreoperative serum AGR levels independently predicted the risk of disease progression in patients with NMIBC. However, it was not found to be associated with either RFS or PFS in NMIBC patients based on their EAU risk group. This marker seems to have a limited role in NMIBC at the present time. However, further research is needed to investigate this marker in combination with other systemic inflammatory markers to help improve prediction in this heterogeneous group of patients.

Project description:BackgroundBladder carcinoma is a type of urological tumor with high risks of recurrence and progression. The triglyceride-glucose (TyG) index has demonstrated significant promise as a prognostic marker for metabolic health in different types of cancer. Further research is needed to explore the relationships among non-muscle-invasive bladder cancer (NMIBC), the TyG index, and its prognostic importance. Purpose of this preliminary research is to assess the predictive significance of the TyG index for recurrence and progression risk in NMIBC patients.MethodsData from patients admitted between October 2018 and July 2021 were reviewed, and there are 198 patients in total were included. The experimental data were supplied by medical records. In addition, patient prognoses were followed up via telephone. Furthermore, patients were separated into two groups: the high and low TyG groups, using X-tile software. Apart from recurrence-free survival (RFS), progression-free survival (PFS) was the main outcome. According to the TyG index, nomograms were also established.ResultsThe cohort consisted of 93 patients in the high TyG group and 105 patients in the low TyG group. The TyG index was a key prognostic factor for postoperative RFS (HR = 2.726, 95% CI = 1.474-5.041, p = 0.001) and PFS (HR = 2.846, 95% CI = 1.359-5.957, p = 0.006) among patients with NMIBC. The log-rank test revealed a notable disparity between the low and high TyG groups regarding RFS (p = 0.0025) and PFS (p = 0.0110). Moreover, it was strongly connected to well-known NMIBC risk factors. Because the TyG index exhibited good predictive value, the nomogram models were formulated.ConclusionThe TyG index serves as an isolated predictor of both RFS and PFS among patients with NMIBC, revealing new insights into disease treatment mechanisms. Indeed, the TyG index serves as a credible indicator of risk classification while facilitating early intervention among patients with NMIBC.

Dataset Information

Prognostic Value of BUB1 for Predicting Non-Muscle-Invasive Bladder Cancer Progression.

Publications

Prognostic Value of BUB1 for Predicting Non-Muscle-Invasive Bladder Cancer Progression.

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