Clinical significances of p27 in digestive tract cancers: a comprehensive analysis on immunohistochemistry staining, published literatures, microarray and RNA-seq data

Abstract

In the present study, we conducted a comprehensive analysis on the clinical roles of p27 protein and p27 gene in digestive tract cancers (DTCs). First, we performed immunohistochemistry staining and found that p27 protein was down-regulated in DTCs. Then we collected 62 publications and calculated the combined hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (95% CIs) to clarify the relationships of p27 protein expression with prognoses and clinicopathological parameters. The overall HRs indicated that the down-regulated p27 protein was an independent prognostic biomarker for overall survival (HR: 1.58, 95% CI: 1.38–1.81, P < 0.0001) but not for disease–free survival and cancer–specific survival. The combined ORs indicated that a low expression of p27 protein was positively related to lymph node metastasis (OR: 2.15, 95% CI: 1.57–2.96, P < 0.0001), distant metastasis (OR: 2.02, 95% CI: 1.12–3.63, P = 0.019) and pathology grading (OR: 2.14, 95% CI: 1.75–2.62, P < 0.0001). Additionally, 60 DTCs-related microarray and RNA-seq datasets were obtained to investigate the expression level and clinical value of p27 gene in DTCs patients. We found that the expression level of p27 gene in DTCs was similar to that in normal controls. And no significant associations of p27 gene expression with prognoses and clinicopathological factors were observed. In conclusion, according to our results, it was p27 protein, but not p27 gene, that can function as an effective biomarker to predict the clinical outcome in patients with DTCs. The down-regulation of p27 protein in DTCs may not result from the altered expression of p27 gene.