Low expression of CDK12 in gastric cancer is correlated with advanced stage and poor outcome

Abstract

Background: Cyclin-dependent kinase 12 (CDK12) belongs to the cyclin-dependent kinase (CDK) family, modulating multiple cellular functions including DNA damage response (DDR), development and cellular differentiation, transcription, mRNA processing, splicing and pre-mRNA processing. CDK12 has been reported as both tumor suppressor and oncogene in various kinds of tumor. The function of CDK12 in gastric cancer (GC) remains unclear.

Methods/results: CDK12 mRNA expression was decreased in GC compared with non-tumor tissue based on GEO database. Also, low mRNA expression of CDK12 was detected in GC cell lines by qPCR. Similarly, CDK12 protein expression was also reduced in GC tissues compared with adjacent non-tumor tissues in 177 GC patients as shown by immunohistochemistry. Low expression of CDK12 was associated with organ metastasis, poorly differentiated adenocarcinoma and advanced stage. Consistent with human protein atlas database analysis, Low expression of CDK12 was correlated with worse overall survival (P < 0.001). Multivariate Cox regression indicated that low expression of CDK12 was an independent prognostic factor for GC patients (P < 0.001). Finally, a gene set enrichment analysis was performed to detect underlying internal mechanisms and biological processes.

Conclusions: CDK12 is down-regulated in GC and its expression is negatively correlated with advanced stage, poorly differentiated adenocarcinoma and poor outcomes. Our findings suggest that CDK12 may be a potential tumor suppressor in GC.

Keywords: CDK12; Cyclin-dependent kinase 12; Gastric cancer; Prognosis.