Introduction

Bladder cancer (BC) is a common cancer of the urinary tract, with an estimated 573,278 new cases and 212,536 deaths annually worldwide [1]. The disease is clinically classified into nonmuscle invasive bladder cancer (NMIBC)(Ta/T1) and muscle-invasive bladder cancer (MIBC)(T2-T4), based on different clinical progressions and prognoses. Despite advancements in current therapeutic methods, including surgery, radiation therapy, and chemotherapy, the 5-year overall survival (OS) rate remains unsatisfactory, particularly for advanced bladder cancer [2,3,4]. Therefore, finding a novel biomarker as an effective therapeutic target to improve the prognosis of bladder cancer patients is crucial.

Bladder cancer (BC) has been extensively studied for prognostic markers [5,6,7,8,9]. CTCs have emerged as potential prognostic markers in various cancers [10,8, 21]. Given these limitations and uncertainties, there is a need for improved prognostic biomarkers in BC to enhance clinical management and treatment decisions.

B7-H3 (CD276) belongs to the B7 superfamily of molecules and shows potential as a promising target for cancer treatment. The expression of the B7-H3 protein has been observed in various tumor tissues, including non-small cell lung cancer (NSCLC) and prostate cancer, and it is closely associated with tumor progression, metastasis, recurrence, and other adverse clinical features [22,23,55,56,57,58]. These results have paved the way for clinical trials focusing on B7-H3 targeting. In the context of bladder cancer, Ma et al. [59] demonstrated an increase in CD69 expression on activated T cells (ATC) when treated with an anti-CD3-B7-H3 bispecific antibody (B7-H3Bi-Ab). CD69 is considered an early activation marker for T cells. B7-H3Bi-Ab-ATC have the capability to eliminate B7-H3-positive bladder cancer cells through the CD3-B7-H3 bridge mechanism, exhibiting significant cytotoxic activity against human bladder cancer cells. These findings suggest that B7-H3Bi-Ab enhances the killing potential of ATC against bladder cancer cells, offering a promising novel approach for the treatment of bladder cancer.

Although efforts have been made, our study still has some limitations. Firstly, the main ethnic populations were European and Asian, and African representation was insufficient. Secondly, the pooled analyses of the relationships between B7-H3 expression and prognosis and patient clinicopathological features, such as tumor grade and T stage, were based on a relatively small number of studies. More research is needed to validate these results and obtain more reliable conclusions. Thirdly, the included studies used different criteria for judging the positive or negative expression of B7-H3, leading to some heterogeneity in the meta-analysis. This could affect the overall accuracy of the results. Fourthly, we did not include unpublished articles and conference abstracts in the meta-analysis due to insufficient information, which may introduce selection bias and potentially miss relevant data. Fifthly, the sample size of our meta-analysis was relatively small, which may limit the statistical power to detect certain associations, especially in the analysis of overall survival. Lastly, because some included articles did not report detailed survival data, we had to rely on the Kaplan-Meier curve for survival analysis, which might lead to potential overestimation or underestimation of actual survival data. To address these limitations, future research should focus on conducting well-designed clinical randomized controlled studies with larger sample sizes that encompass diverse racial backgrounds to provide more robust and comprehensive insights into the relationship between B7-H3 expression and bladder cancer.

Conclusion

In conclusion, our study confirms that B7-H3 is overexpressed in bladder cancer (BC), and its expression is closely related to tumor invasion and recurrence in BC. Furthermore, B7-H3 expression has shown no association with the survival of bladder cancer patients, suggesting that B7-H3 may play multiple roles in the pathophysiology of bladder cancer. To address the limitations of the current meta-analysis, it is imperative that future studies with larger sample sizes and standardized methodologies be conducted. Additionally, investigating the underlying mechanisms by which B7-H3 influences tumor progression holds the potential to contribute to the development of innovative treatment strategies for bladder cancer.