Correlation Of EGFR Mutation With ERCC1 And TYMS MRNA Expression In Non-small Cell Lung Cancer

Background and purposeFor patients with locally advanced non-small cell lung cancer (NSCLC) who miss the opportunity of surgical treatment, chemotherapy still plays an important role. Prognosis may vary due to the differences of the individual case’s tumor genes, even they have the same type of pathology and chemotherapy regimens. In recent years, as the tumor molecular biology research deepened and high-throughput detection technology continues to progress, the molecular target genetic testing plays more and more important role in the individual treatment of NSCLC. Previous studies have found that epidermal growth factor receptor (EGFR) mutation was closely related to the sensitivity of platinum-based and pemetrexed chemotherapy drugs in NSCLC. We all know that nucleotide excision repair cross complement 1 (ERCC1) and thymidylate synthase (TYMS) are related genes of platinum and pemetrexed chemotherapy drugs, respectively. The goal of this study is to detect the EGFR mutations and the mRNA expression of ERCC1 and TYMS in NSCLC, to analyze EGFR gene mutations in NSCLC and its correlation with clinical characteristics (gender, histological type, smoking, etc.), thus to investigate the relationship between the EGFR mutations and ERCC1 and TYMS mRNA expression.Materials and MethodsRetrospective study was applied. Ninety seven patients with NSCLC (Department of Thoracic Surgery, Daping Hospital, The Third Military Medical University) were enrolled into this study between February 2013 to December 2013 All the tumor tissue samples were obtained by operation or puncture and confirmed by pathology. mRNA expression of ERCC1 and TYMS genes were detected by branched-DNA liquid chip, while somatic mutations in EGFR (E18, E19, E20, E21) gene were detected by x-TAG liquid chip. Correlation between EGFR gene mutation and ERCC1, TYMS mRNA expression was analyzed.Results1. In the 97 specimens, EGFR gene mutation was found in 29 cases, the mutation rate was 30%. The most common mutation was the 21th point mutation in outer exon (48%, 14/29) and the 19th deletion mutation in outer exon (37.9%,11/29). Besides, there were a small number of 18th exon mutation (6.8%,2/29) and 20th exon mutation (6.8%,2/29), and one case of 18th and 20th exon co-mutation (3.4%,1/29).2. EGFR gene mutation rate in women (70%,21/30) was significantly higher than men (11.9%,8/67), P<0.05. Mutation rate in non-adenocarcinoma (0%,0/37) was significantly lower than adenocarcinoma (48.3%,29/60), P<0.05). Mutation rate in smoker (12.7%) was lower than patients with no history of smoking (52.3%), P<0.05. However, there was no significant difference in EGFR mutation rates between patients aged ≤60 year-old (11, 22%) and those aged>60 years (18,38.2%), P>0.05. Moreover, there was no significant difference in EGFR mutation rates between tumor stage Ⅰ and Ⅱ (17,36.9%) and tumor stage Ⅲ and Ⅳ (12,23.5%), P>0.05.3. Among the 29 cases of mutation EGFR gene, the negative mRNA expression rate of ERCC1 was 62%(18/29), the positive rate was 37.9%(11/29). In the 68 cases of wild-type EGFR gene, the negative rate of ERCC1 mRNA expression was 39.7%(27/68), the positive rate was 60.2%(41/68). Compared with patients not detected EGFR mutations in NSCLC, EGFR mutation patients with ERCC1 mRNA negative expression was more common (chi-square=4.088, P< 0.05). However the ERCC1 mRNA expression had no obvious correlation with the clinical features (P> 0.05).4. Among the 29 cases of EGFR gene mutation, the negative expression rate of TYMS mRNA was 58.6%(17/29), the positive rate was 41.3%(12/29). In the 68 cases of wild-type EGFR gene, the negative rate of TYMS mRNA expression was 52.9%(36/68), the positive rate was 47%(32/68). The TYMS mRNA had no obvious correlation with the EGFR mutations (χ2=0.265, P>0.265) nor clinical features (P>0.05).Conclusion1. EGFR mutations were common in female, adenocarcinoma lung cancer patients without smoking history. Most of the mutations were found in 19th and 21th outer exon.2. Compared with patients not detected EGFR mutations in NSCLC, EGFR mutation patients with ERCC1 mRNA negative expression was more common. NSCLC patients with EGFR mutation may have a better outcome using platinum chemotherapy drug.3. There is no significant correlation between EGFR gene mutation and TYMS mRNA expression.