Correlative analysis of gene mutation and clinical features in patients with non-small cell lung cancer

Xiao Kuang, Jian Xiao, Long-Xia Dai, Li-Hai Zhang, Bi-Xiu He


Background: Lung cancer is the main reason for death associated with cancer all over the world. In most cases of non-small cell lung cancer (NSCLC), patients only express one type of gene mutation, each gene mutation population has different clinicopathological features, and each is expressed differently in different regions of the population. At present, there are few studies on multiple driver genes and clinicopathological features of the population in Hunan, China.
Methods: From February 2016 to December 2017, the Department of Geriatric Respiratory Medicine of Xiangya Hospital of Central South University diagnosed 113 cases of NSCLC. Genetic testing of next-generation sequencing (NGS) was completed, and it conformed to the inclusion criteria. All cases were pathologically confirmed as NSCLC, with the tumor staging being based on the 8th edition of TNM classification.
Results: In this study, we included a total of 113 NSCLC cases, including 78 males and 35 females. Histological distributions were mainly adenocarcinoma (ADC, 78.76%) and squamous cell carcinoma (SCC, 21.24%). We found 71 cases had gene-mutations. There was one concurrent mutation of ALK and ROS1, one concurrent mutation of epidermal growth factor receptor (EGFR) and BRAF, one concurrent mutation of EGFR and MET, one concurrent mutation of MET and BRAF, and one concurrent mutation of EGFR and KRAS; there were two cases of concurrent mutation of EGFR and ERBB2. The distribution of each of the mutated genes was as follows: EGFR, 62.82%; ALK, 8.97%; ROS1, 5.13%; MET, 5.13%; ERBB2, 5.13%; RET, 0.00%; BRAF, 2.56%; KRAS, 10.26%. Our study found that in patients with EGFR mutation, the mutation rate of males was 32.05%, and the rate in females was 68.57% (P<0.01); the mutation rate in people aged 60 or above was 40.00% while for those aged lower than 60 it was 46.55% (P>0.05); the mutation rate of ADC was 52.81% and in SCC was 8.33% (P<0.01); the mutation rate in smokers was 32.84% and in non-smokers was 58.70% (P<0.05); the mutation rate in patients of IV stage was 47.37% and the rate in patients of non-IV stage was 22.22% (P>0.05). Our study found that among patients with ALK/ROS1/MET/ERBB2/BRAF/KRAS mutations, the mutation rate in men was 7.69%, 2.60%, 3.85%, 2.56%, 0.00%, and 8.97% respectively, and for females it was 2.86%, 5.71%, 2.86%, 5.71%, 5.71%, and 2.86% respectively; the mutation rate in patients aged 60 and older was 3.64%, 5.45%, 3.64%, 1.82%, 1.82%, and 9.09% respectively; the rate in patients aged lower 60 was 8.62%, 1.72%, 3.45%, 5.17%, 1.72%, and 5.17% respectively; the mutation rate of ADC was 6.74%, 3.37%, 3.37%, 4.49%, 2.25%, and 6.74% respectively, while for SCC, it was 4.17%, 4.17%, 4.17%, 0.00%, 0.00%, and 8.33% respectively; the mutation rate in smokers was 8.96%, 1.49%, 4.48%, 1.49%, 0.00%, and 10.45% respectively, while in non-smokers, it was 2.17%, 6.52%, 2.17%, 6.52%, 4.35%, and 2.17% respectively; the mutation rate in patients of IV stage was 7.37%, 4.21%, 2.11%, 4.21%, 2.11%, and 7.37% respectively, and in patients of non-IV stage, it was 0.00%, 0.00%, 11.11%, 0.00%, 0.00%, and 5.56% respectively. In ALK/ROS1/MET/ERBB2/BRAF/KRAS mutations, there was no statistically significant difference in gender, age, tissue type, smoking history, and stage. Our research shows that the distribution of each mutant type of EGFR mutation was as follows: exon 2, 1/74 (1.35%); exon 4, 1/74 (1.35%); exon 6, 1/74 (1.35%); exon 18, 1/74 (1.35%); exon 19, 25/74 (33.78%); exon 20, 12/74 (16.22%); exon 21, 19/74 (25.68%); exon 22, 1/74 (1.35%); and EGFR amplification, 13/74 (17.57%).
Conclusions: (I) EGFR mutation was more common in non-smoking female patients with ADC and had no significant correlation with age and stage. (II) EGFR mutations were mainly concentrated in exon 19, 20, 21, and EGFR amplification. There was no significant statistical difference between mutations in exons 19, 20, 21, EGFR gene amplification and clinical features. (III) There was no statistically significant difference in the ALK/ROS1/MET/ERBB2/BRAF/KRAS mutations with gender, age, tissue type, smoking history, and tumor stage.