Expression Analysis of TPD52, Kruppel-like factors (KLF 9), PKCε and MicroRNA 223: Possible Biomarkers in Cervical and Ovarian Cancer

Abstract

Gynecologic cancers constitute a group of malignancies that arise in the female reproductive parts of the body. Cervical and ovarian are the leading types of gynecologic tumors. Ovarian cancer ranks as the 6th most frequent cancer in terms of incidence and 7th on the basis of death globally. While cervical cancer is the second most prevalent cancer in women globally. In Pakistani women tumor of cervix is the third most common tumor. Stage at which a particular tumor is diagnosed mainly determines a patient‘s survival rate. In Pakistan, greater than 70% malignancies are diagnosed at higher grade. Although various screening techniques are being used for diagnosis of ovarian and cervical cancer but the death rate in developing states continues to be high. Pap smear test is the most influential technique used for cervical cancer diagnosis. But in countries like Pakistan it continues to remain ineffective due to financial constraints. Similarly for diagnosis of ovarian cancer different techniques are used such as CA-125 is used as a biomarker for ovarian carcinoma. But its levels in serum may also be linked with other diseases. Hence identifying improved screening and diagnostic strategies have become the essential need in cancer research studies. This study aimed to identify new blood based biomarkers linked with prognosis and diagnosis of ovarian and cervical cancer. In the current study co-expresssion of TPD52, KLF 9, miR-223 and PKCε was evaluated in the peripheral blood of ovarian and cervical cancer patients and a possible correlation with disease outcome was revealed. The expression of TPD52, KLF 9, miR-223 and PKCε was studied in blood of 50 ovarian and 50 cervical cancer patients relative to 50 healthy controls using real time PCR. The statistical analysis was performed by ordinary one-way ANOVA and ordinary 2-way ANOVA using Graph pad prism 6.0 software. There was 12 and 23 fold increase in TPD52 expression, 2 fold increase in miR-223 expression, 0.0044 and 0.14 fold decrease in KLF9 expression, 0.1 and 0.05 fold decrease in PKCε expression in ovarian and cervical cancer respectively. In the present study we observed an association of TPD52, KLF 9, miR-223 and PKCε with tumor stage, metastasis and treatment response in ovarian and cervical cancer. The elevated expression of TPD52, miR-223 and reduced expression of KLF 9 and PKCε in peripheral blood of ovarian and cervical cancer patients may serve as a predictor of disease prognosis, metastasis as well as treatment response in such tumors. Nevertheless, further studies are required to strengthen their role as a potential diagnostic and prognostic biomarker in these cancers.