Abstract

Purpose. We aimed to comprehensively review contemporary literature on genetic and epigenetic biomarkers associated with the prediction of Bacillus Calmette-Guerin (BCG) response after the transurethral resection of a bladder tumor and to discuss the application of these biomarkers in precision cancer care for bladder cancer. Method. We performed a systematic review of published literatures in the databases PubMed and Embase by using the following key words: bladder cancer, BCG, gene, and methylation. Studies associated with cell lines, animal models, and muscle invasive bladder cancer were excluded. Results. The genetic variations associated with BCG response can be classified into three categories: germline variations, somatic variations, and epigenetic alterations. Genes related to BCG response were mainly involved in single-nucleotide polymorphisms, copy number variations, and gene methylations. Conclusions. Although these gene alterations are currently the most promising predictive markers of BCG response, most studies about bladder cancer DNA biomarkers are related to germline variations in candidate genes, and the results are not consistent. Only one study is related to somatic variation, and further evaluation in large-scale validation studies should be conducted to assess the potential clinical application of these findings. In addition, other biomarkers based on different “–omics” technologies should be considered in future studies.

Highlights

  • Bladder cancer (BC) is the most common malignancy of the urinary tract and the 7th most common cancer in men and the 17th in women [1]

  • 75% of bladder cancer patients are nonmuscle invasive bladder cancer (NMIBC), which can be treated with transurethral resection of bladder tumor (TURBT)

  • We aimed to review the contemporary literature on biomarkers predicting Bacillus Calmette-Guerin (BCG) response, in genetics and epigenetics

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Summary

Background

Bladder cancer (BC) is the most common malignancy of the urinary tract and the 7th most common cancer in men and the 17th in women [1]. For patients with intermediate-risk and high-risk tumors, intravesical fulldose Bacillus Calmette-Guerin (BCG) instillation is recommended as the first choice of treatment [2]. Nearly 40% of patients do not respond to intravesical BCG therapy and experience disease recurrence or progression, which leads to a poorer prognosis [3, 4]. Using mitomycin or other chemotherapy agents for bladder instillation in patients who do not response to BCG may improve the disease prognosis. Genetic alterations in single nucleotides in numerous pathways were found to be closely associated with BCG response. Various genetic copy number alterations were associated with bladder cancer [7]. We aimed to review the contemporary literature on biomarkers predicting BCG response, in genetics and epigenetics

Evidence Acquisition
Germline Variations
Findings
Conclusion
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