Genomic evidence of lung carcinogenesis associated with coal smoke in Xuanwei area, China

Zhang, Honglei; Liu, Chao; Li, Li; Xu, Feng; Wang, Qing; Li, Jihua; Xu, Shi‐Hai; Wang, Zhen; Yang, Qianlu; Zy, Shen; Su, Jinhua; Su, Xiaohong; Chen, Wenhui; Sun, Ruili; Zhou, Xuhong; Wang, Junliang; Zhou, Yunyun; Jiao, Baowei; Ding, Wanbao; Cao, Xianbao; Huang, Yunchao; Ye, Lianhua

doi:10.1093/nsr/nwab152

Cited by 10 publications

(17 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The probable reason for these results was that most patients (2146) in the study of Zhou et al were only tested for ALK and ROS1 gene fusions using the ARMS-PCR method, while here we applied NGS exome sequencing for detection of all mutation sites in these genes. Other authors like Zhang et al detected EGFR mutations in 52.68% of tumor samples from Xuanwei lung cancer patients, followed by TP53 (41.07%) and KRAS (7.14%) [11], which was consistent with our results. The screening of the gene KRAS in our studies was quite different from Zhang et al [11] as in this study, and the authors included only 117 never-smoking women with lung adenocarcinoma.…”

Section: P R E P R I N Tsupporting

confidence: 93%

“…Other authors like Zhang et al detected EGFR mutations in 52.68% of tumor samples from Xuanwei lung cancer patients, followed by TP53 (41.07%) and KRAS (7.14%) [11], which was consistent with our results. The screening of the gene KRAS in our studies was quite different from Zhang et al [11] as in this study, and the authors included only 117 never-smoking women with lung adenocarcinoma. Compared with the Yunnan population (except the Qujing population) [12], NSCLC patients in eastern Yunnan coal-producing areas had lower mutation rates of EGFR and ALK genes and higher mutation rates of KRAS, BRAF, PIK3CA, and NTRK1 genes (Figure 2).…”

Section: P R E P R I N Tsupporting

confidence: 93%

“…Zhou et al also found that EGFR, KRAS, and ALK were the driver genes in lung cancer patients from Qujing [12]. Zhang et al found that EGFR, TP53, RBM10, and KRAS were the driver genes in 117 lung cancer patients from Xuanwei [11]. Another study analyzed 84 lung cancer patients from Xuanwei based on genome-wide sequencing and RNA expression profiles.…”

Section: Analyses Of Nsclc Driver Genes and Signaling Pathwaysmentioning

confidence: 99%

“…In general, we had a controversy about the driver genes of NSCLC in the coal-manufacturing Yunnan districts. The possible factors for this were: (1) the obtained results were from a limited sample size [50]; (2) they were inconsistent when detecting part of the exome and P r e p r i n t the whole exome [11]; (3) the regional distribution of the included patients was inconsistent in the coalproducing provinces of Xuanwei, Qujing and Eastern Yunnan [12].…”

Section: Analyses Of Nsclc Driver Genes and Signaling Pathwaysmentioning

confidence: 99%

“…However, the mutation rates in genes like KRAS [9] and the tumor protein p53 (TP53) [10] were higher. Furthermore, the whole-exome sequencing (WES) of lung cancer and distal normal tissues from 112 Xuanwei patients with early lung adenocarcinoma found mutations in EGFR, KRAS, TPRN, and SPTLC1 genes were identified as driver mutations for individuals with lung P r e p r i n t cancer from the region of Xuanwei [11]. Other authors detected 10 driver genetic mutations in 526 NSCLC lung cancer patients from Qujing city.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Unique Spectrum of Driver Gene Mutations in Patients with Non-Small Cell Lung Carcinoma (NSCLC) from Coal-manufacturing Districts in Southwest China

Wang

Yang

et al. 2022

Arch Med Sci

View full text Add to dashboard Cite

IntroductionThe coal-manufacturing districts in the Eastern Yunnan province of Southwest China are the utmost occurrence and death of lung tumors. As previously reported on unique clinical characteristics of non-small cell lung cancer (NSCLC) in patients from these regions without a clear understanding of the aetiology and molecular characteristics. We aim to identify the unique driver gene mutations spectrum.Material and methodsSamples from 1120 NSCLC patients from Eastern Yunnan were gathered for next-generation sequencing. Seventeen gene targets were sequenced. We have compared individuals' medical and genetic features from the coal- and non-coal-manufacturing zones.ResultsThe mutation rates of EGFR (L858R, 19-Del, G719X+L861X, L858R+EGFR amplification) and ERBB2 (20ins) were low in patients from coal-manufacturing regions. Interestingly, EGFR (G719X, S768I, G719X+S768I), KRAS (G12C), TP53 (R158L) and NTRK3 demonstrated a much higher mutation frequency. Furthermore, EGFR compound mutations were linked with the patient's job and TNM staging IIIb-IV. The OncodriverCLUST algorithm authenticated 6 genes (KRAS, EGFR, ROS1, NRAS, BRAF, and ERBB2) as driver genes in patients from coal manufacturing. EGFR with KRAS, BRAF, RET, and TP53 with ALK and KRAS were mutually exclusive. Mutations in the TP53 signaling pathway were the most common in NSCLC patients from the coal-fabricating districts.ConclusionsOur analyses confirmed the unique spectrum of driver genetic mutations and emphasized the potential of future targeted therapy in NSCLC patients from the coal-manufacturing districts of Eastern Yunnan. Our data broaden the view of NSCLC pathogenesis and its relationship with the environmental conditions in coal-producing regions.

show abstract

Section: P R E P R I N Tsupporting

confidence: 93%

Section: P R E P R I N Tsupporting

confidence: 93%

Section: Analyses Of Nsclc Driver Genes and Signaling Pathwaysmentioning

confidence: 99%

Section: Analyses Of Nsclc Driver Genes and Signaling Pathwaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Unique Spectrum of Driver Gene Mutations in Patients with Non-Small Cell Lung Carcinoma (NSCLC) from Coal-manufacturing Districts in Southwest China

Wang

Yang

et al. 2022

Arch Med Sci

View full text Add to dashboard Cite

show abstract

Identification of core carcinogenic elements based on the age-standardized mortality rate of lung cancer in Xuanwei Formation coal in China

Chen,

Cheng,

Wang

et al. 2024

Sci Rep

View full text Add to dashboard Cite

In this study, the core carcinogenic elements in Xuanwei Formation coal were identified. Thirty-one samples were collected based on the age-standardized mortality rate (ASMR) of lung cancer; Si, V, Cr, Co, Ni, As, Mo, Cd, Sb, Pb, and rare earth elements and yttrium (REYs) were analyzed and compared; multivariate statistical analyses (CA, PCA, and FDA) were performed; and comprehensive identification was carried out by combining multivariate statistical analyses with toxicology and mineralogy. The final results indicated that (1) the high-concentration Si, Ni, V, Cr, Co, and Cd in coal may have some potential carcinogenic risk. (2) The concentrations of Cr, Ni, As, Mo, Cd, and Pb meet the zoning characteristics of the ASMR, while the Si concentration is not completely consistent. (3) The REY distribution pattern in Longtan Formation coal is lower than that in Xuanwei Formation coal, indicating that the materials of these elements in coal are different. (5) The heatmap divides the sampling sites into two clusters and subtypes in accordance with carcinogenic zoning based on the ASMR. (6) PC1, PC2, and PC3 explain 62.629% of the total variance, identifying Co, Ni, As, Cd, Mo, Cr, and V. (7) Fisher discriminant analysis identifies Ni, Si, Cd, As, and Co based on the discriminant function. (8) Comprehensive identification reveals that Ni is the primary carcinogenic element, followed by Co, Cd, and Si in combination with toxicology. (9) The paragenesis of Si (nanoquartz), Ni, Co, and Cd is an interesting finding. In other words, carcinogenic elements Ni, Co, Cd, and Si and their paragenetic properties should receive more attention.

show abstract

Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities

Zhang,

Liu,

Wang

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Air pollution significantly impact lung cancer progression, but there is a lack of a comprehensive molecular characterization of clinical samples associated with air pollution. Here, we performed a proteogenomic analysis of lung adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke is the primary contributor to the high lung cancer incidence. Genomic mutation analysis revealed XWLC as a distinct subtype of LUAD separate from cases associated with smoking or endogenous factors. Mutational signature analysis suggested that Benzo[a]pyrene (BaP) is the major risk factor in XWLC. The BaP-induced mutation hotspot, EGFR-G719X, was present in 20% of XWLC which endowed XWLC with elevated MAPK pathway activations and worse outcomes compared to commonEGFRmutations. Multi-omics clustering of XWLC identified four clinically relevant subtypes. These subgroups exhibited distinct features in biological processes, genetic alterations, metabolism demands, immune landscape, tumor microbiota composition and radiomic features. Finally,MAD1 and TPRNwere identified as novel potential therapeutic targets in XWLC. Our study provides a valuable resource for researchers and clinicians to explore prevention and treatment strategies for air-pollution-associated lung cancers.

show abstract

Genomic evidence of lung carcinogenesis associated with coal smoke in Xuanwei area, China

Cited by 10 publications

References 9 publications

Unique Spectrum of Driver Gene Mutations in Patients with Non-Small Cell Lung Carcinoma (NSCLC) from Coal-manufacturing Districts in Southwest China

Unique Spectrum of Driver Gene Mutations in Patients with Non-Small Cell Lung Carcinoma (NSCLC) from Coal-manufacturing Districts in Southwest China

Identification of core carcinogenic elements based on the age-standardized mortality rate of lung cancer in Xuanwei Formation coal in China

Proteogenomic analysis of air-pollution-associated lung cancer reveals prevention and therapeutic opportunities

Contact Info

Product

Resources

About