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Loss of CDKN2A and CDKN2B expression is associated with disease recurrence in oral cancer

V G Deepak Roshan^1,2, M S Sinto¹, Bipin T Vargees³

¹Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, Kerala, India.

Journal of Oral and Maxillofacial Pathology : JOMFP

|May 22, 2019

Abstract

Background:

Loco-regional recurrence is one of the major reasons for poor prognosis of oral squamous cell carcinoma (OSCC). However, till date, no feasible molecular marker is available to predict the risk of recurrence in OSCC patients.

Aim:

To evaluate the cell cycle regulatory genes expression and its association with the risk of recurrence in oral cancer patients.

Materials And Methods:

Transcript level expressions of 47 cell cycle regulatory genes were analyzed in 73 OSCC tumors from buccal mucosa and tongue, 26 adjacent normal samples using real-time polymerase chain reaction. TaqMan low-density array data were analyzed using the DataAssist™ v 3.01. Significantly altered genes within the tumor samples and samples showing recurrence (re-appearance of disease during the follow-up in cases having complete response to initial treatment assessed after 3 months of the treatment) were identified. Further, Kyoto Encyclopedia of Genes and Genomes pathway analysis and The Cancer Genome Atlas (TCGA) online data analysis portal were used to analyze interacting protein and pathways significantly associated with the altered gene.

Results:

CCNA1, CCNB2, CCND2, CCNE1, CCNF, CDC2, CDK6, CHEK1, and TGFA found to significantly alter in the tumor sample of oral cancer patients, and down-expression of CDKN2A and CDKN2B found to associate with the recurrence of disease in oral cancer patients. TCGA data also showed the loss of CDKN2A and CDKN2B significantly associated with recurrence in head and neck cancer patients.

Conclusion:

CDKN2A and CDKN2B expression analysis can be used as the prognostic marker for the oral cancer patients. The present method of data analysis helps overcome the limitations and complications of high throughput techniques and thereby increases the opportunity of employing molecular markers in routine clinical management of OSCC.

Keywords:

Biomarker TaqMan low-density array cell cycle oral carcinoma recurrence

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