期刊
FRONTIERS IN ONCOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.819003
关键词
CDK6; urothelial carcinoma; CDK4; 6 inhibitor; precision medicine; immunohistochemistry staining
类别
资金
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2017YFC0110105]
- Young Scientists Fund of the National Natural Science Foundation of China [81700198]
- Science and Technology Development Project of Jilin Province [20190701064GH]
- Open Project of Key Laboratory of Tumor Immunology and Pathology (Army Medical University), Ministry of Education [2018jsz101]
- Natural Science Foundation of Jilin province [20210101252JC]
CDK6 protein expression in urothelial carcinoma can be used as a screening platform for CDK4/6 inhibitor targeted therapy.
BackgroundInfiltrating bladder urothelial carcinoma is the most common bladder malignancy with limited therapeutic options and poor prognosis. Identifying new therapeutic targets or strategies has important clinical significance. The data from public sources indicate poor prognosis in urothelial carcinoma cases with high CDK6 mRNA levels. Furthermore, studies have shown that CDK6 expression is elevated in urothelial carcinoma tissue compared to the surrounding urothelium, thus presenting a case for performing CDK4/6 inhibitor targeted research in urothelial carcinoma. However, a phase II trial showed that CDK4/6 inhibitors are not effective for advanced urothelial carcinoma, suggesting that case screening is important for targeted therapy. ObjectiveImmunohistochemistry (IHC) is simple and easy to perform and can be used to screen urothelial carcinoma cases with high CDK6 expression in clinical practice. The aim of this study was to determine the CDK6 expression threshold for positive cases. MethodsWe evaluated the correlation between the H-score of CDK6 protein expression and survival or CDK6 mRNA level using RNA sequencing. The effects of different CDK4/6 inhibitors were tested on bladder carcinoma cell lines with different CDK6 expression levels. ResultsThe H-score, which predicts poor prognosis and reflects a high CDK6 mRNA level, was determined as the selection criterion for positive cases. Furthermore, we found that urothelial carcinoma cell lines with higher CDK6 expression levels displayed greater sensitivity to CDK4/6 inhibitors than cells with lower expression levels. ConclusionsIHC staining for CDK6 protein in urothelial carcinoma is proposed as a promising screening platform for CDK4/6 inhibitor targeted therapy.
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