Open AccessPredictive 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
Author(s) -
Niki Karachaliou,
Chara Papadaki,
Eleni Lagoudaki,
Maria Trypaki,
Maria Sfakianaki,
Anastasios Koutsopoulos,
Dimitris Mavroudis,
Efstathios N. Stathopoulos,
Vassilis Georgoulias,
John Souglakos
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0074611
Subject(s) - ercc1 , etoposide , medicine , oncology , cisplatin , chemotherapy , biology , gene , biochemistry , nucleotide excision repair , dna repair
Background 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). Methods 184 SCLC patients’ primary tumour samples were analyzed for ERCCI, BRCA1, ATP7B, PKM2 TOPOI, TOPOIIA , TOPOIIB and C-MYC mRNA expression. All patients were treated with cisplatin-etoposide. Results 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 ERCC1 ( p =0.028), PKM2 ( p =0.046), TOPOI ( p =0.008), TOPOIIA ( p =0.002) and TOPOIIB (p<0.001) mRNA had a shorter Progression Free Survival (PFS). In limited stage patients, high expression of ERCC1 ( p =0.014), PKM2 ( p =0.026), TOPOIIA ( p =0.021) and TOPOIIB ( p =0.019) was correlated with decreased median overall survival (mOS) while in patients with extended stage, only high TOPOIIB expression had a negative impact on Os ( p =0.035). The favorable expression signature expression signature (low expression of ERCC1 , PKM2, TOPOIIA and TOPOIIB ) was correlated with significantly better PFS and Os in both LS-SCLC ( p <0.001 and p =0.007, respectively) and ES-SCLC ( p =0.007 and ( p =0.011, respectively) group. The unfavorable expression signature was an independent predictor for poor PFS (HR: 3.18; p =0.002 and HR: 3.14; p =0.021) and Os (HR: 4.35; p= 0.001and HR: 3.32; p =0.019) in both limited and extended stage, respectively. Conclusions Single gene’s expression analysis as well as the integrated analysis of ERCC1 , PKM2, TOPOIIA and TOPOIIB may predict treatment outcome in patients with SCLC. These findings should be further validated in a prospective study.