The Expression Of CDK6 And Its Clinical Significance In Cervical Cancer

Background: Cervical cancer is the second most common in gynecologic tumors and the mainly cause of deaths among women in developing countries.Although the early screening reduces the mortality of cervical cancer patients,but invasion and metastasis were the mainly cause of cervical cancer.Consequently,the identification of novel biomarkers and development of new therapeutic approaches are of great value for cervical cancer.Cycline dependent kinase 6(CDK6),which associate with D-type cyclins,phosphorylate and inactivate retinoblastoma(Rb),thereby promoting cell-cycle entry from G1 to S phase.CDK6 is a critical component in the biology of human tumors,protecting cancer cells against apoptosis and promoting cancer angiogenesis.Cheng et al.have shown that CDK6 is elevated in several malignancies,such as lymphoma,pancreatic cancer,breast cancer,bladder cancer and lung cancer.Moreover,overexpression of CDK6 is responsible for a number of processes involved in tumour progression,including apoptosis,lymphangiogenesis,migration,associated with the metastasis of some tumors such as breast cancer and nasopharyngeal carcinoma,indicating the significance of CDK6 as a potential target for cancer therapy.Until now,the significance of CDK6 in cervical cancer has not been well understood.The aim is to investigate the expression and clinicopathological significance of CDK6 in cervical cancers.Objectives: To explore the expression level and localization of CDK6 protein in cervical cancer;To analyze the correlation between the high expression of CDK6 protein and clinicopathological parameters and prognosis of cervical cancerMethods: A total of 138 cervical cancer patients with strict follow-up,62 cervical intraepithelial neoplasias(CIN),18 normal cervical epithelia tissues were selected for immunohistochemical staining of CDK6 protein.The correlations between CDK6 overexpression and the clinical features of cervical cancer were evaluated using chi-square test and Fisher's exact tests.The Human Protein Atlas,Onco Lnc cohort,GEPIA cohort,and TCGA cohort were used to verify the value of evaluation of CDK6 in prognosis of the cervical cancer patients.Results:(1)CDK6 protein is highly expressed in cervical cancer tissues,mainly in the nucleus and a small amount in the cytoplasm.The rate of positive CDK6 protein expression was only 22.2%(4/18)in normal cervical epithelia tissues,but significantly higher in CIN lesions(60.0% in CIN-1,63.2% in CIN-2 and 56.5% in CIN-3)and cervical cancer(79.7%,110/138)of the cervix(P<0.01,respectively).(2)Pearson's ?2 test showed that the abnormal expression of CDK6 protein was significantly associated with clinical stage(P=0.024),differentiation(P=0.001),lymph node metastasis(P=0.001)and HPV-infected(P=0.000)but not with age and histological types.(3)The Human Protein Atlas,Onco Lnc cohort,GEPIA cohort,and TCGA cohort showed that abnormal expression of CDK6 was closely related with cervical cancer survival(P<0.05).Conclusions:(1)CDK6 is abnormally and strongly expressed in cervical cancer.(2)High-level expression of CDK6 was related with clinical stage,differentiation,lymph node metastasis and HPV-infected.(3)CDK6 expression is shown as a potential biomarker of clinical outcomes in patients with cervical cancer and should be evaluated in prospective trials.