NPC is a unique malignant head/neck cancer with remarkably distinctive ethnic and geographic distribution among the world.Though there are some other neoplasms such as lymphoma, carcinoma of salivary gland and rare melanotic disease , NPC is the most common in nasopharyngeal region. It is a disease with disorder of cell cycle and uncontrolled growth due to abnormal expression of cell cycle factors [4, 6, 16]. P27, a key cell cycle protein kinase inhibitor, formed a complex with CCND1 and CDK4 that prevents CDK4 from adding phosphate residues to its principal substrate, the retinoblastoma (pRb) protein and blocks the cell-cycle G1/S transition. Furthermore, p27 is able to bind other Cdk proteins when it connected to cyclin subunits such as Cyclin A/Cdk2 and Cyclin E/Cdk2 and suppress the transition of cell cycle. Decreased expression of p27 has been indicated in many tumors, including lung cancer , bladder cancer , melanoma , and ovarian cancer , prostate cancer , which was associated with the unfavorable clinical parameters and poor outcomes of these tumors. However, the role of p27 is still unclear in NPC.
In a previous investigation, we found the significantly attenuated levels of p27 mRNA in NPC tissues and cells compared to NP tissues  by gene microarray analysis. In this study, we validated the significantly differential expression of mRNA in NPC tissues and NPC cells compared to NP tissues by real-time PCR. Our reports were similar with the investigation of p27 mRNA expression in other tumors [17–19]. Furthermore, we also found that reduced mRNA p27 expression was shown in clinical stage of III-IV compared to clinical stage of I-II. These results preliminarily suggested p27 as a potentially suppressive gene involved in the pathogenesis of NPC.
In subsequent exploration, we observed that p27 protein was a co-expression factor of cytoplasm and nucleus in NPC tissues and nearly a half of NPC cases showed nuclear expression of p27. In line with the mRNA expression examination, p27 protein expression was significantly down-regulated in NPC tissues compared to NP tissues. This result further provided evidence to support p27 as a candidate suppressor in NPC. Further, we analyzed the correlation of p27 protein expression with clinical features of NPC patients. We found that although p27 protein expression was not associated with patient’s age, sex, smoking, N classification (lymph node metastasis) or M classification (distant metastasis), it was positively correlated with T classification (tumor size) and clinical stage. This result was similar to our report of p27mRNA expression of in NPC. Furthermore, we presented the evidence that protein expression of p27 protein in NPC was inversely correlated with patient’s overall survival time. Patients with high protein expression of p27 had an overall longer survival time. Our results here suggest that p27 protein expression is taken as a tumor suppressor inhibiting the pathogenesis of NPC.
Furthermore, survival prognosis was assessed by stratification analysis against different T classification, N classification, M classification, and clinical stage. We observed that p27 protein expression was only positively associated with the survival time for NPC patients in N0-1 classification. Patients with high p27 expression had better prognosis than those of negative nuclear expression. These results hinted that p27 expression is a good biomarker for evaluating the prognosis of NPC patients with N0-1 classification.
Finally, we evaluate the possibility of p27 protein expression as an independent prognostic factor. According to univariate analysis, patient’s overall survival is inversely proportional to T/N/M classification, clinical stage, but positively correlated with p27 protein expression and radiotherapy. Multivariate analyses showed that nuclear expression of p27 protein was not an independent predictor of prognosis for NPC patients regardless of its patients’ disease status. This result was not consistent with the reports from other tumors including breast cancer  and glioma  etc.
In summary, our results provide evidence that expression of p27 may be involved in the clinical progression and poor prognosis of NPC patients. However, it could not serve as a potential independent prognostic factor for NPC patients.