Expression of p27 and p16 and their clinical significance in gastric cancer

Abstract

Deregulated expression of cell cycle regulators p27 and p16 is associated with cancer progression. p27kip1 and p16INKa are a cyclin dependent kinase inhibitor whose major target is the cyclinE/CDK2 and cyclinD/CDK4/6 complex, respectively, that governs cell cycle transition from late G1 to S phase. We recruited biopsies of a total of 84 subjects including 72 primary tumor biopsies from histopathologically proven gastric carcinoma, 8 adjacent controls and 12 independent controls. We used gastric cancer cell line, AGS, for validation of our data. Expression profiling at transcript level was done by semi-quantitative RT-PCR and at proteome level by immunohistochemistry and immunofluorescence. Receiver operator characteristics analysis was done for determining the diagnostic utility of p27 and p16 with respect to the sensitivity and specificity. We demonstrate that p27 and p16 are frequently over expressed in early stages of gastric carcinoma. Our semi-quantitative data show a significant upregulation of p27 (Mean ± SEM, 0.4771 ± 0.0895; p = 0.0001) and p16 (Mean ± SEM, 0.4676 ± 0.04305; p = 0.0001) at mRNA level. Concordant to semi-quantitative data, immunohistochemistry data also showed a significant upregulation of p27 (Mean ± SEM, 196.4 ± 10.84; p < 0.0001) and p16 (Mean ± SEM, 100.4 ± 23.71; p < 0.0001) at protein level. The present study showed that the significant upregulation of p27 and p16 were associated with early events in gastric carcinogenesis. Our data suggests that clinical correlation of these differentially expressed genes may be useful as diagnostic biomarkers for early detection of gastric carcinoma and promising therapeutics target for GC patients.