Predictive Value of BRCA1, ERCC1, ATP7B, PKM2, TOPOI, TOPΟ-IIA, TOPOIIB and C-MYC Genes in Patients with Small Cell Lung Cancer (SCLC) Who Received First Line Therapy with Cisplatin and Etoposide

Abstract

<div><p>Background</p><p>The aim of the study was to evaluate the predictive value of genes involved in the action of cisplatin-etoposide in Small Cell Lung Cancer (SCLC).</p> <p>Methods</p><p>184 SCLC patients’ primary tumour samples were analyzed for <i>ERCCI, BRCA1, ATP7B, PKM2</i><i>TOPOI, TOPOIIA</i>, <i>TOPOIIB</i> and <i>C-MYC</i> mRNA expression. All patients were treated with cisplatin-etoposide.</p> <p>Results</p><p>The patients’ median age was 63 years and 120 (65%) had extended stage, 75 (41%) had increased LDH serum levels and 131 (71%) an ECOG performance status was 0-1. Patients with limited stage, whose tumours expressed high <i>ERCC1</i> (<i>p</i>=0.028), <i>PKM2</i> (<i>p</i>=0.046), <i>TOPOI</i> (<i>p</i>=0.008), <i>TOPOIIA</i> (<i>p</i>=0.002) and <i>TOPOIIB</i> (p<0.001) mRNA had a shorter Progression Free Survival (PFS). In limited stage patients, high expression of <i>ERCC1</i> (<i>p</i>=0.014), <i>PKM2</i> (<i>p</i>=0.026), <i>TOPOIIA</i> (<i>p</i>=0.021) and <i>TOPOIIB</i> (<i>p</i>=0.019) was correlated with decreased median overall survival (mOS) while in patients with extended stage, only high <i>TOPOIIB</i> expression had a negative impact on Os (<i>p</i>=0.035). The favorable expression signature expression signature (low expression of <i>ERCC1</i>, PKM2, <i>TOPOIIA</i> and <i>TOPOIIB</i>) was correlated with significantly better PFS and Os in both LS-SCLC (<i>p</i><0.001 and <i>p</i>=0.007, respectively) and ES-SCLC (<i>p</i>=0.007 and (<i>p</i>=0.011, respectively) group. The unfavorable expression signature was an independent predictor for poor PFS (HR: 3.18; <i>p</i>=0.002 and HR: 3.14; <i>p</i>=0.021) and Os (HR: 4.35; <i>p=</i>0.001and HR: 3.32; <i>p</i>=0.019) in both limited and extended stage, respectively.</p> <p>Conclusions</p><p>Single gene’s expression analysis as well as the integrated analysis of <i>ERCC1</i>, <i>PKM2, TOPOIIA</i> and <i>TOPOIIB</i> may predict treatment outcome in patients with SCLC. These findings should be further validated in a prospective study.</p> </div