P3.03-039 Prognostic Biomarkers for Malignant Pleural Mesothelioma Treated with Chemotherapy: Topic: Mesothelioma Clinical

Abstract

Prognosis of Malignant Pleural Mesothelioma (MPM) is poor and median survival is about 12 months. If any associations can be established between biomarkers and MPM, there will be benefit to clinical practice. In this study, the aim is to examine expression levels of the genes selected from relevant literature and utilizing in silico methods in the determination of prognosis of MPM. The study group consisted of 54 MPM patients treated by chemotherapy. The expression of 6 genes; sestrin 1 (SESN1), laminin subunit alpha 4 (LAMA4), midkine (MKN), fibulin-3 (EFFL-3), syndecan-1 (SOC-1) and hyaluronan-2 (HYA-2) were examined by qPCR in the tumor tissues. SESN1 and LAMA4 were identified using an in house R based script “Unsupervised Survival Analysis Tool.” MKN, EFFL-3, SOC1 and HYA-2 were determined according to existing literature. We used two housekeeping genes; glucose-6-phosphate dehydrogenase (G6PD), TATA-box binding protein (TBP) as controls. qPCR Relative quantification of gene expression was based on the geometric mean G6PD, TBP. The relation between gene expression and prognosis was determined by categorizing samples into two groups using all possible cut-off values, analyzed by the Log Rank test (Log-rank test with multiple cut-offs). Cut-offs generating a p value less than 0.05, between %10-90 percentiles were considered significant. Mean age of study group was 62.5± 9.7 years (r:36-82). Of the patients, 43 (79.6%) had epithelioid cell type mesothelioma. The median survival (MS) for all patients was 10 (±1.18 SE) months (CI 95%;7.69 to 12.30). Twenty-five patients (46.3%) survived less than 12 months, 29 (53.7%) more than 12 months, and 4 (7.4%) were still surviving at the end of the study. The clinical factors that was associated with survival were histopathology (p=0.004) and stage (p=0.036). MKN, EFFL-3, SOC1, HYA-2, SESN-1 were found to be associated with survival time by univariate analyses. After the correction with histopathology and stage, MKN (p=0.041), SOC1 (p=0.015), HYA-2 (p=0.003), SESN-1 (p=0.028) were found to be related with survival time. Additionally, in only epithelioid type MPM patients, HYA-2 expression was found to be related with survival time according to multivariate analyses (p=0.016). High MKN expression is potential biomarker of poor prognosis and high SOC1, HYA-2, SESN-1 expressions are potential biomarkers of good prognosis in MPM patients, and should be further investigated. High HYA-2 expression also can be utilized as good prognosis biomarker for epithelioid type MPM. *This study was partly supported by General Directorate of Health Researches, Republic of Turkey, Ministry of Health.