The current study aimed to evaluate the frequency and types of epidermal growth factor receptor (EGFR) mutations in lung cancer patients. Following this evaluation, EGFR gene mutations were observed in 19.8% of participants. Most of these mutations (57%) were nucleotide deletions, and the replacement was in the following category (42.1%). In one case (0.9%), nucleotide deletion and replacement were observed simultaneously.
Mutations are not limited to a change in just one nucleotide (replacing one nucleotide with another nucleotide); they also include deletions, insertions, and duplication, which necessitates the study of the genome in different diseases, including cancer. Among the various types of cancer, lung cancer is the most common cause of cancer-related death among American men and women. The number of deaths due to lung cancer is higher than the total number of deaths due to breast, prostate, and colorectal cancer together (2). Hence, it is essential to investigate lung cancer, looking for possible mutations affecting the diagnosis, treatment, and prognosis of this cancer, as the deadliest cancer globally.
One of the biological changes that might be related to lung cancer is the mutation of the EGFR oncogene (25). Epidermal growth factor receptor (EGFR) is a cell membrane protein with tyrosine kinase activity, which has various functions, such as cell growth, proliferation, and differentiation (21). Numerous studies demonstrated an association between the EGFR gene polymorphism and advanced stages of various cancers, such as lung and gastric cancer [26, 27]. The presence of a mutation in the EGFR gene activates the receptor on the cell surface (17). Besides, this receptor induces cell survival by inhibiting apoptotic pathways (18,19). EGFR mutations have been revealed to be associated with responsiveness to receptor antagonist drugs (such as gefitinib) in patients with non-small cell lung carcinoma (NSCLC) (26,27). Reports have also shown that allelic forms of this gene are involved in lung cancer (28,29). In addition, the gene polymorphisms of this receptor might be related to race and geographical conditions and vary in different populations, so that the rate of polymorphism in the American people is 2% and in the Japanese population is 26% (18,20). Therefore, it seems essential for each country and region to investigate the rate and frequency of this mutation among its people.
In the current study, in 113 of the total 570 samples (19.8%), EGFR mutations have been detected. However, in Iranian patients with esophageal cancer, the incidence of EGFR mutation was higher, and Lashkarizadeh et al. reported that 82% of the 60 samples were mutated (30). In our study, 65 cases (57%) of all mutations were in the form of deletion. In 48 patients (42.1%), nucleotide replacement was present, and a combined nucleotide deletion and replacement coexisting simultaneously were observed in only one case (0.9%). In the study of Lashkarizadeh et al., in 52% of cases, the mutation was of the gene deletion type, in 30% of the cases, the mutation was seen as gene duplication, and in other cases, both types of mutation were detected simultaneously (30). In this study, most of the deletion mutations occurred in exon 19 (about 94%), while most of the replacement mutations occurred in exon 21 (about 79%). In the study of EGFR mutations in patients with esophageal cancer, the most deletion mutations were in exon 2 (44%), and the highest rate of replacement mutations (54%) was in exon 27 (30).
In a similar study by Dr. Basi and colleagues on lung adenocarcinoma, EGFR mutations were observed in 25 of 103 patients (24.3%), which is inconsistent with the value obtained in our study (24). In Dr. Basi's study, the most common sites of mutations were exon 21 (15 patients; 60%) followed by exon 19 (10 patients; 40%); although in our study, it was the other way around, and the mutations in exon 19 (62 patients; 54.9%) occurred more frequently than Exon 21 (42 patients; 37.2%), following by exon 18 mutation (8 patients; 7.1%). In this study, the overall incidence of mutation in women (70 patients; 61.9%) was significantly higher than in men (43 patients; 38.1%). It was in contrast with the study of Dr. Basi et al., in which the incidence of mutations was equally distributed between men and women (24). In our study, the incidence of deletion mutations in women was significantly higher than in men. Still, there was no significant difference between the two sexes in terms of replacement mutations. However, in the study of Dr. Basi, no similar investigation has been done.
Investigating biomarkers in blood, urine, and tissue is becoming appropriate markers for early cancer detection (31,32). Accordingly, various studies have been performed on the possibility of using different tumor biomarkers for lung cancer screening. Plasma microRNAs, circulating tumor cells, and autoantibodies are presented as possible biomarkers for lung cancer diagnosis (33–35). In other studies, the serum level of Carcinoembryonic antigen (CEA) in patients with non-small-cell lung cancer was higher than the other types of cancer (36,37). Moreover, another study on 184 patients revealed a relation between lung cancer involvement and CK19 and CEA serum levels (38). Hence, advances in biomarkers and genomic fields are considered the future of cancer investigation, and EGFR as an important proven marker could be used in this regard. Consequently, its frequency in different populations could play an important role in planning treatment guidelines for lung cancer in each country.
In conclusion, the association of the EGFR gene mutation with lung cancer has been indicated, so investigation of EGFR mutation could help decide about patients' therapeutic plan, such as anti-EGFR drug usage. The frequency of EGFR mutation in lung cancer patients referred to a specialized lung disease hospital has been investigated. A higher frequency among Iranian patients than the western population has been obtained. However, the frequency seems to be almost the same as the eastern population.
Further multi-centric studies with a higher number of participants, other genomic evaluations, and investigating the possible application of this mutation for screening and early detection of cancer among the different population are recommended.