Expression of cyclin-dependent kinases and their clinical significance with immune infiltrates could predict prognosis in colorectal cancer.

INTRODUCTION

Colorectal cancer (CRC) is one of the most cancer-related mortalities worldwide and remains a major public health issue. Despite several attempts to develop promising therapies for CRC, its survival rate decreases with metastasis. Cyclin-dependent kinases (CDKs) are a family of protein kinases with various regulatory activities including cell cycle, mRNA expression, transcription, and differentiation. Aside from their role in cell proliferation when mutated, abnormal expression of these genes has been reported in some human cancer subtypes. This study explored the roles and therapeutic potentials of CDK 1 and 4 as prognostic biomarkers in CRC.

METHODS

Bioinformatics analyses were carried out to demonstrate the expression and prognostic values of CDK-1 and CDK-4 with immune infiltrate in CRC.

DISCUSSION

CDK levels in CRC were remarkably higher than those in normal tissues ( < 0.05), and overexpression in CRC tissues was significantly related to nodal metastatic status ( < 0.05) and histological subtypes. Kaplan-Meier analyses showed that patients with CRC who exhibited CDK-1 overexpression had worse overall survival (OS) as against patients with CDK-4 overexpression. The alteration observed was a mutation while the mutation hotspots include E163* and R24A/C/H/L respectively for CDK-1 and CDK-4 on the Pkinase domain. Of the associated genes, AURKA and RB1 were predominantly altered. Furthermore, CDK-4 is positively correlated with tumor purity in both COAD and READ while CDK-1is only positively correlated in COAD. CDK-1 overexpression was significantly associated with poor prognosis as opposed to CDK-4.

CONCLUSION

The expression and prognostic values of AURKA and RB1 may also be significant to CRC diagnosis. CDKs together with the co-expressed genes and their association with immune infiltrates may serve as target molecules for immunotherapy in CRC.