Different subtypes of EGFR exon19 mutation can affect prognosis of patients with non-small cell lung adenocarcinoma

• Published in: PloS one Vol. 13; no. 11; p. e0201682
• Main Authors: Tian, Yingying, Zhao, Jiuzhou, Ren, Pengfei, Wang, Bo, Zhao, Chengzhi, Shi, Chao, Wei, Bing, Ma, Jie, Guo, Yongjun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-11-2018; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenocarcinoma of Lung - diagnosis; Adenocarcinoma of Lung - drug therapy; Adenocarcinoma of Lung - genetics; Aged; Amino acid sequence; Amino acids; Base Sequence; Biology and Life Sciences; Cancer therapies; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Clinical outcomes; Clonal deletion; Codons; Drug therapy; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; Exons; Female; Gene deletion; Gene mutations; Genetic aspects; Growth factors; Humans; Kinases; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lungs; Male; Medical prognosis; Medical records; Medicine and Health Sciences; Mutation; Nucleotides; Pathology; Patients; Prognosis; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Retrospective Studies; Sequence Deletion; Survival; Systematic review; Tyrosine; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0201682

In this study, we determined whether different subtypes of epidermal growth factor receptor (EGFR) exon19 mutation are associated with the therapeutic effect of EGFR-tyrosine kinase inhibitors (TKIs) on advanced non-small cell lung adenocarcinoma.
A total of 122 patients with stage III or IV non-small cell lung adenocarcinoma were retrospectively reviewed. Clinical characteristics of these patients, including progression-free survival (PFS) outcome for EGFR-TKI treatment, were analyzed.
According to the mutation pattern, we classified the in-frame deletions detected on EGFR Exon19 into three different types: codon deletion (CD), with a deletion of one or more original codons; codon substitution and skipping (CSS), with a deletion of one or two nucleotides but the residues could be translated into a new amino acid without changing following amino acid sequence; CD or CSS plus single nucleotide variant (SNV) (CD/CSS+SNV), exclude CD or CSS, there's another SNV nearby the deletion region. The clinical characteristics of three groups were analyzed and as a result, no significant difference was found. By comparing the average number of missing bases and amino acids of the three mutation subtypes, it could be discovered that the number of missing bases and amino acids of the three mutation subtypes is diverse, and group CSS> group CD> group CD/CSS+SNV. Finally, survival analysis was performed between three groups of patients. The median PFS of group CD, group CSS and group CD/CSS+SNV was 11 months, 9 months and 14 months respectively. There was a distinct difference in the PFS between group CSS and group CD/CSS+SNV (P = 0.035<0.05), and the PFS of group CD/CSS+SNV was longer.
Different mutation subtypes of EGFR exon19 can predict the therapeutic effect of EGFR-TKIs on advanced non-small cell lung adenocarcinoma.