Study On ERCC1 Expression And Single Nucleotide Polymorphism Related To Sensitivity Of Squamous-cell Lung Carcinomas To Cisplatin In Vitro

Objective:To determine the relationship between ERCC1 expression , ERCC1 codon 118 single nucleotide polymorphisms and sensitivity of squamous-cell lung carcinomas to cisplatin in vitro, providing important theoretical evidence to guide cisplatin's individual chemotherapy in lung cancer field.Methods:1. 42 fresh operative squamous-cell lung carcinoma samples were collected and immediately used to be tested the sensitivity to cisplatin with the method of ATP-tumor chemosensitivity assay.2. The expression of ERCC1 protein in 42 paraffin-embedded samples of squamous-cell lung cancer was determined through immunohistochemical analysis (S-P method).3. ERCC1 codon 118(C→T) single nucleotide polymorphism of each samples was determined by polymerase chain reaction-restrictive fragment length polymorphism(PCR-RFLP).4. Analyze the relationship between ERCC1 protein expression , ERCC1 codon 118(C→T) single nucleotide polymorphism and sensitivity of squamous-cell lung carcinomas to cisplatin in vitro. :Results: 1. There were 22(52.4%) cases sensitive to cisplatin in the 42 squamous-cell lung carcinomas specimen, and still another 20(47.6%) resistant cases.2. There were 8(36.4%) cases with sensitve to cisplatin in vitro in the 22 cases of ERCC1-positive group, and 14(70.0%) sensitive cases in the 20 cases of ERCC1-negative group. The sensitivity to cisplatin of ERCC1-positive group was significantly lower than the negative group (P <0.05).3. 17(40.5%) cases were homozygous for AAC codon (C/C genotype) of ERCC1 codon 118, 15(35.7%) were homozygous for AAT codon (T/T genotype), and 10 (23.8%) were heterozygous (C/T genotype).The response rate to cisplatin of T/T+C/T genotypes was 68.0%, and C/C genotype was 29.4%. That is , those with at least one T allele(T/T+C/T) had a better response to cisplatin than those without a T allele (C/C ) (P <0.05). 4. ERCC1 protein expression may be related to ERCC1 codon 118(C→T) polymorphism, and our data suggested that ERCC1-positive rate was significantly lower in the patients with at least one T allele(T/T+C/T) compared with C/C genotype (P <0.05).Conclusions: 1. ERCC1-positive expression may be related to squamous-cell lung cancer's resistance to cisplatin.2. Patients with at least one T allele(T/T+C/T) of ERCC1 codon 118 may benefit a lot from cisplatin compared with those without a T allele (C/C ).3. ERCC1-positive rate was significantly lower in the patients with T/T+C/T genotypes compared with those with the C/C genotype, which would explain why those with T/T+C/T genotypes had a better response to cisplatin than those with C/C genotype.4. There may be close relationship between ERCC1 protein expression, ERCC1 codon 118 (C→T) single nucleotide polymorphism and sensitivity to cisplatin, ERCC1 is expected to be a prognostic factor of squamous-cell lung cancer's chemotherapy with cisplatin .