Unique characteristics of G719X and S768I compound double mutations of epidermal growth factor receptor (EGFR) gene in lung cancer of coal-producing areas of East Yunnan in Southwestern China

Abstract

Background: The principal objective of this project was to investigate the Epidermal Growth Factor Receptor (EGFR) gene mutation characteristics of lung cancer patients, which can provide a molecular basis for explaining the clinicopathological features, epidemiology and use of targeted therapy in lung cancer patients in the coal-producing areas of East Yunnan.

Methodology: We collected 864 pathologically confirmed lung cancer patients' specimens in First People's Hospital of Qujing City of Yunnan Province from September 2016 to September 2021. We thereafter employed Next Generation Sequencing (NGS) technology to detect all exons present in the EGFR gene.

Results: The overall mutation frequency of the EGFR gene was 47.22%. The frequency of EGFR gene mutations in the tissue, plasma, and cytology samples were found to be 53.40%, 23.33%, and 62.50%, respectively. Univariate analysis indicated that the coal-producing areas and Fuyuan county origin were significantly associated with relatively low EGFR gene mutation frequency. Female, non-smoking history, adenocarcinoma, non-brain metastasis, and tissue specimens were found to be related to high EGFR gene mutation frequency. Multivariate logistic regression analysis suggested the lung cancer patients in the central area of Qujing City, stage Ia, non-coal-producing areas, non-Fuyuan origin, and non-Xuanwei origin were more likely to develop EGFR gene mutations. The most common mutations were L858R point mutation (33.09%) and exon 19 deletion (19-del) (21.32%). Interestingly, the mutation frequency of G719X (p = 0.001) and G719X + S768I (p = 0.000) in the coal-producing areas were noted to be more significant than those in non-coal-producing regions.

Conclusion: This findings of this study might be important in establishing the correlation between routine using NGS for EGFR gene mutation diagnosis and clinical practice in the lung cancer patients.

Keywords: Coal-producing areas; EGFR gene mutation; G719X and S768I compound double mutation; Lung cancer.

Fig. 1

A map of 9 counties in Qujing City has been shown to the township. The solid black square (■) indicates the different towns in the coal-producing areas. The Yunnan province map is on the left, and the Guizhou province map is on the right

Fig. 2

EGFR gene mutation spectrum in a coal-producing areas, b non-coal-producing areas, c overall area population. The lung cancer patients in Yunnan eastern coal-producing belts displayed more unusual G719X, G719X + S768I, but relatively lesser L858R and 19-del mutations compared to the non-coal-producing belts patients

Fig. 3

Distribution of EGFR gene point mutation types in the 864 patients affected with lung cancer. The difference was considered as statistically significant when p < 0.05 (bar chart marked with *). P-values were set at 0.01 (p < 0.01) for the highly significant differences (bar chart marked with **), and 0.001 (p < 0.001) for extremely significant difference (bar chart marked with ***)