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. 2023 Sep 14;9(10):e20171.
doi: 10.1016/j.heliyon.2023.e20171. eCollection 2023 Oct.

Different gene alterations in patients with non-small-cell lung cancer between the eastern and southern China

Chengdong Liu  1 , Kangbao Li  2 , Yi Sui  3 , Hongmei Liu  3 , Yunzhi Zhang  3 , Yuan Lu  4 , Wei Lu  4 , Yongfeng Chen  4 , Gehui Wang  3 , Suqian Xu  3 , Tianmin Xiang  3 , Yongguang Cai  4 , Kenan Huang  5   6
Affiliations

Different gene alterations in patients with non-small-cell lung cancer between the eastern and southern China

Chengdong Liu et al. Heliyon. .

Abstract

Geographical differences are conspicuous in lung cancer, and the distinct molecular features of lung tumor between Western patients and Asian patients have been demonstrated. However, the etiology of non-small-cell lung cancer (NSCLC) and the distribution of associated molecular aberrations in China have not been fully elucidated. The mutational profiles of 12 lung cancer-related genes were investigated in 85 patients from eastern China and 88 patients from southern China who had been histologically confirmed NSCLC. Overall, 93.6% (162/173) of tumor samples harbored at least one somatic alteration. The most frequently mutated genes were TP53 (56.1%), EGFR (50.3%), and KRAS (14.5%). We found that EGFR mutated much more frequently (60.0% vs 40.9%, P = 0.012) and TP53 mutations had significantly lower incidence (47.1% vs 64.8%, P = 0.019) in eastern cohort than that in southern cohort. Mutational signature analysis revealed a region-related mutagenesis mechanism characterized by a high prevalence of C to T transitions mainly occurring at CpG dinucleotides in southern patients. This study reveals the difference in the mutational features between NSCLC patients in eastern and southern China. The distinct patterns of gene mutation could provide clues for the mechanism of carcinogenesis of lung cancer, offering opportunities to stratify patients into optimal treatment plans based on genomic profiles.

Keywords: C > T transitions; Lung cancer; Region-related; gene mutations.

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Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: YS, HL, YZ, GW, SX and TX were employed by company Singlera Genomics (Shanghai). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Mutational landscape and clinical characteristics of 162 NSCLC patients with at least one somatic alteration. The X-axis represents 81 patients from eastern China (A) and 81 patients from southern China (B), respectively. The Y-axis represents the mutated genes and the corresponding mutation frequency in all patients (the left column), eastern patients (the middle column) and southern patients (the right column). Clinical characteristics and alteration types are annotated in different colors.
Fig. 2
Fig. 2
Correlation between clinical characteristics and genetic alterations in NSCLC patients. (A-C) Correlation between gender (A), smoking history (B), and stage (C) with EGFR mutation in all patients. (D, E) Correlation between gender (D) and smoking history (E) with KRAS mutation in all patients. (F) Correlation between stage with TP53 mutation in all patients.
Fig. 3
Fig. 3
Comprehensive analysis of genetic mutations in eastern and southern NSCLC patients. (A, B) Comparison of number of patients with EGFR or TP53 mutation between the two cohorts. (C, D) The clinical characteristics of patients with common driver mutations in eastern and southern cohorts.
Fig. 4
Fig. 4
Base substitutions of SNVs in eastern and southern NSCLC. (A) Different class of the base substitutions of SNVs between eastern and southern patients. (B) Percentage of patients with C > T transitions localized in CG, CT, CA, and CC dinucleotides. (C, D) The prevalence of mutated genes with C > T transitions in eastern and southern patients.
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