Comprehensive Analysis of the Significance of Cyclin Dependent Kinase Inhibitor Genes in the Prognosis of Cervical Cancer

Introduction

Cell division is controlled by cyclin-dependent kinases and cyclins whose expression is prominently regulated by the binding to CDK inhibitors. Here, the most targeted CDK family genes (CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, and CDKN2D) and known as CDK inhibitors was taken for the interaction analysis.

Aim

The study sought to uncover and comprehend the expression patterns of CDK inhibitors in  cervical cancer by applying bioinformatic analysis to patient data that was made publicly available.

Materials

In this study, the bioinformatics tools (GEPIA, Kaplan Meier plotter analysis, cBioPortal, UALCAN, Cytoscape and FunRich) were used to predict the most interacted gene among all the genes in CDK gene family. UALCAN analysis used to analyze the relative expression of CDK family genes. The Kaplan–Meier Plotter survival analysis used to identify prognostic value of expressions of CDK gene family. Functional protein interaction network construction and the Retrieval of Interacting Genes were done using (STRING) database. Gene function annotation and pathway enrichment analysis Gene ontology (GO) analysis was done by DAVID tool.

Results

The stage-specific expression results revealed that all seven inhibitors are expressed differently at distinct stages of cervical cancer (I–IV). A strong correlation was found between the shorter survival of patients with cervical cancer and the high expression of CDKN2C (HR value = 0.54, P = 0.013) and low expression of CDKN2D (HR value = 0.45, P = 0.0011). Patients with cervical cancer had a significantly shorter survival rate when their levels of CDKN1A (HR value = 0.36, P = 0.032), CDKN1C (HR value = 2.23, P = 0.04), and CDKN2B (HR value = 0.27, P = 0.023) were highly expressed. The majority of genomic alterations were explained by CDK inhibitor-induced gene amplification and mutation frequencies.

Conclusion

This study highlighted that cyclin dependent kinase inhibitor expression may be a gene to target for cervical cancer. As a biomarker and therapeutic target, it may be employed in the detection and management of cervical cancer.

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