High-level mRNA of excision repair cross-complementation group 1 gene is associated with poor outcome of platinum-based doublet chemotherapy of advanced nonsmall cell lung cancer patients.
BACKGROUND
DNA excision repair gene expression plays a pivotal role in the resistance of platinum-based doublet chemotherapy of nonsmall cell lung cancer (NSCLC) in clinical practice. The aim of this study was to investigate the relationship of the excision repair cross-complementation group 1 (ERCC1) mRNA level in fresh tumor tissue and the efficacy of platinum-based chemotherapy of NSCLC.


METHODS
100 patients diagnosed with NSCLC, including stage IIIB with malignant pleural effusion, stage IV, and recurrent disease, were enrolled in this study. Before clinical treatment, tumor biopsy specimens were collected, and total RNA was purified to analyze ERCC1 mRNA level by real-time polymerase chain reaction assay. All patients were treated with platinum-based third-generation doublet chemotherapy.


RESULTS
Patient median age was 60 years. Forty-seven patients had NSCLC with low expression of ERCC1 mRNA, and 53 patients had high expression of ERCC1 mRNA. Although the ERCC1 mRNA level was not correlated with the response rate (p = .665) and progression-free survival (median, 6.4 months vs. 5.5 months; p = .446), the high level of ERCC1 mRNA demonstrated a significant association with poor overall survival (median, 11 months vs. 17 months; p = .02). High level of ERCC1 mRNA was an independent prognostic factor for poor overall survival (p < .001) along with lack of disease control (p < .001).


CONCLUSIONS
High level of ERCC1 mRNA may serve as a useful prognostic factor for poor outcome in advanced NSCLC patients treated with platinum-based third-generation doublet chemotherapy and may provide important information to guide tailored therapy of NSCLC patients.
Ren
Shengxiang
S
Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
Zhou
Songwen
S
Zhang
Ling
L
Xu
Jianfang
J
Lv
Meijun
M
Zhang
Jie
J
Zhou
Caicun
C
Zhang
Jie
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; D016190:Carboplatin; C071447:ERCC1 protein, human; D004720:Endonucleases; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine