Long Non-Coding RNA- PVT1 in Ovarian Cancer as Predictors for Platinum Analogues Resistance

Abstract

Abstract Background Ovarian cancer is the fifth most common type of cancer and the most common cause of death among women with gynecological malignancies. Objectives The aim of this retrospective study was to assess expression of the Lnc_PVT1 in the studied subjects. The expression of Lnc_PVT1 biomarker; was compared in ovarian cancer patients versus the non-cancerous tissue. The data normalization was tested by normality test which shows that the biomarker expression is not normally distributed; thus, a Mann Whitney statistics test for non -parametric values was applied. Our results showed a high significant difference in the expression of Lnc-PVT1 (p < 0.01). Lnc_PVT1 expression is upregulated by 2.4 folds in ovarian cancer patients (median: 32.0; range: 11 – 92) compared to control group (median: 13.0; range: 11 – 16). Methods and Materials This is a retrospective study. Include patients with advanced epithelial ovarian cancer (stage II and IV) who received chemotherapy platinum based and taxines from 2014-2017. Setting: Clinical oncology department Ain Shams University, Egypt, Demerdash hospital. Data collection: The following information will be ANONYMOUSLY extracted from the patient medical files: age at diagnosis, presenting symptoms, laboratory investigations: (Liver function, kidney function, complete blood count &tumor markers), tumor histological type, tumor FIGO stage& degree of differentiation, treatment modalities, type of surgery, chemotherapy regimens (Adjuvant, Neoadjuvant or palliative), chemotherapy responsiveness or resistance, disease recurrence and disease-free period, and patients' survival. Results The current study was enrolled on 55 subjects, they classified into two subgroups. The ovarian cancer cases constitute 45 patients; samples collected from patients after diagnosis has been confirmed by histopathology based on immune-histochemical analysis as well as Computerized axial tomography (CT scan) and Magnetic resonance imaging (MRI). The cancer ovary patients were compared to ten non- malignant ovarian tissues. Table 1 illustrates the demographic and clinical data of the studied subjects. We test the normality for age; the data was normally distributed. For this reason, we represent the data in mean value and standard deviation form. Matched age and gender was observed between ovarian cancer patients and healthy control. The mean age for the studied subjects was 47.7±9.1. In our study; the Cisplatin resistant patients (n = 25) had a mean age of 46±5 compared to Cisplatin sensitive which were older (mean: 50 ±11.5). Regarding the age subgroups; the majority of the studied subjects were younger than 48 years old. The ovarian cancer patients were subcategorized into subgroups (Cisplatin sensitive/resistant). Conclusion Comparative analysis between Cisplatin sensitive and resistant ovarian cancer tissues for the Lnc_PVT1, TGF-b and Caspase-3. A high significant difference was observed by Mann- Whitney test (p = 0.001) between Cisplatin sensitive and resistant ovarian cancer patients; Cisplatin resistant tissues showed higher expression levels of the Lnc_PVT1 expression (median 20.0, range: 10 - 92) in Cisplatin sensitive ovarian tissue compared to Cisplatin resistant tissue (median: 83; range: 46-86).