Targeted next generation sequencing identified a high frequency genetic mutated profile in wood smoke exposure-related lung adenocarcinoma patients

Soca-Chafre, Giovanny; Hernández‐Pedro, Norma; Avilés‐Salas, Alejandro; Verson, Carmen Alaez; Sánchez, Karol Carrillo; Cardona, Andrés Felipe; Ávila‐Moreno, Federico; Barrios‐Bernal, Pedro; Flores‐Estrada, Diana; Arrieta, Óscar

doi:10.18632/oncotarget.25369

Cited by 8 publications

(7 citation statements)

References 29 publications

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“…41 Furthermore, EGFR mutations have been associated with biomass fuel exposure, particularly wood smoke exposure, as a risk factor for lung cancer. 42,43 It is possible that our EGFR findings support biomass exposure as a risk factor for lung cancer found in our nonsmokers. Larger, specific studies are needed to confirm this likelihood.…”

Section: Discussionsupporting

confidence: 75%

Clinical Characteristics and Molecular Profiles of Lung Cancer in Ethiopia

Gebremariam

Haisch

Fernandes

et al. 2021

JTO Clinical and Research Reports

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Introduction: Lung cancer is the most common cause of cancer deaths worldwide, accounting for 1.8 million deaths each year. Only 20% of lung cancer cases are reported to occur in low-and middle-income countries. An estimated 1.5% of all Ethiopian cancers involved the lung; however, no nationwide cancer registry exists in Ethiopia. Thus, accurate data on clinical history, histopathology, molecular characteristics, and risk factors for lung cancer are not available. The aim of this study was to describe the clinical, radiologic, and pathologic characteristics, including available molecular profiles, for lung cancer at Tikur Anbessa Specialized Hospital (TASH), the main tertiary referral center in Addis Ababa, Ethiopia. Methods: A cross-sectional study was conducted at TASH among 146 patients with pathologically confirmed primary lung cancer, diagnosed from 2015 to 2019 and recorded in the Addis Ababa Cancer Registry at TASH. Clinical data were extracted from patient medical records, entered into a Research Electronic Data Capture database, and analyzed using Statistical Package for the Social Sciences statistical software. Variables collected included sociodemographics, personal exposures, comorbidities, clinical manifestations at presentation, chest imaging results, diagnostic procedures performed, histopathological classification, cancer staging, and type of treatment (if any). A subset of lung biopsies fixed in formalin for 2 to 7 days, which could be retrieved from the files of the Pathology Department of TASH, were reviewed, and molecular analysis was performed using next-generation sequencing to identify the tumor-oncogenic drivers.Results: Among the 146 patients studied, the mean (SD) age was 54 plus or minus 13 years; 61.6% (n ¼ 90) were male and 25.3% (n ¼ 37) had a history of tobacco use. The most common clinical manifestations included cough (88.4%, n ¼ 129), chest pain (60.3%, n ¼ 88), and dyspnea (53.4%, n ¼ 78). The median duration of any symptoms was 6 months (interquartile range: 3-12 mo). The most common radiologic features were lung mass (84.9%, n ¼ 129) and

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Section: Discussionsupporting

confidence: 75%

Clinical Characteristics and Molecular Profiles of Lung Cancer in Ethiopia

Gebremariam

Haisch

Fernandes

et al. 2021

JTO Clinical and Research Reports

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“…On the other hand, the only factor associated with high CD47 H‐score (≥150) was wood smoke exposure (WSE). Chronic exposure to wood smoke is a common risk factor for lung cancer in Mexico and Latin American countries, WSE affects the expression profiles of genes like EGFR, SMARCB1, ATM, and KDR, and also activates signaling pathways such as PIK3CA/AKT and MAPK . It is known that WSE causes macrophage dysfunction and increases metalloproteinase activity, including MMP‐2 and MMP‐9, leading to cell invasion and migration .…”

Section: Discussionmentioning

confidence: 99%

“…Chronic exposure to wood smoke is a common risk factor for lung cancer in Mexico and Latin American countries, 30 WSE affects the expression profiles of genes like EGFR, SMARCB1, ATM, and KDR, and also activates signaling pathways such as PIK3CA/AKT and MAPK. 30,31 It is known that WSE causes macrophage dysfunction and increases metalloproteinase activity, including MMP-2 and MMP-9, leading to cell invasion and migration. 32 Recently, Xu et al associated higher M1/M2-macrophage infiltration, adenocarcinoma histology and never smokers with CD47 expression in NSCLC tumor.…”

Section: Discussionmentioning

confidence: 99%

Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non‐small cell lung cancer

et al. 2020

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Objective CD47 is an antiphagocytic molecule that contributes to tumor cell resistance in host immune surveillance. CD47 overexpression correlated with tumor progression and shorter survival in lung cancer. However, the expression and functional significance of CD47 in Non‐Small Cell Lung Cancer (NSCLC) has not been completely understood. Materials and Methods In this retrospective study, CD47 expression was immunohistochemically examined in tumor biopsies from 169 NSCLC patients. The association of CD47 levels (H‐score) with clinicopathological characteristics and survival outcomes was evaluated. Results CD47 protein was detected in 84% of patients with a median expression of 80% (0‐100). Tumor CD47 levels above 1% and 50% were found in 84% and 65.7% of patients, respectively. While, median CD47 staining index was 160 (0‐300). Patients were divided into two groups according to CD47 expression (high or low), using a cutoff value of 150. High CD47 expression was associated with wood smoke exposure (71.1% vs 28.9%, P = .013) and presence of EGFR (+) mutations (66.7% vs 33.3%, P = .04). Survival analysis carried out in the whole population did not show any association of CD47 expression and survival outcome. However, in patients with EGFR (+) mutations, CD47 expression was associated with higher progression‐free survival (PFS) (12.2 vs. 4.4 months, P = .032). When the survival analysis was performed according to CD47 levels (cut off value: 150), both, PFS and overall survival (OS) were shortened in patients with a high expression of CD47 (10.7 vs. NR, P = .156) and (29.2 vs. NR months P = .023), respectively. Conclusions CD47 overexpression is not a prognostic factor for PFS and OS in NSCLC patients. However, the presence of EGFR mutations and high expression of CD47 were associated with shortened PFS and OS. Coexpression of these markers represents a potential biomarker and characterizes a therapeutic niche for lung cancer.

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“…The TruSeq Cancer Panel (llumina, CA) for 212 amplicons and 48 cancer-related genes was employed as previously described. 13 Quality control for concentration and size of genomic libraries was performed with a Quantus fluorometer and a 2100 Bioanalyzer (Agilent Technologies, CA, USA). Targeted sequencing was performed on a MiSeq instrument, with an average sequencing depth per base of 1000X.…”

Section: Library Construction and Next-generation Sequencingmentioning

confidence: 99%

Mutational profile by targeted next generation sequencing of non-small cell lung cancer in the Mexican population

Hernández‐Pedro¹,

Soca-Chafre²,

Aláez-Verson³

et al. 2019

Salud Publica Mex

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Objective. Targeted next-generation sequencing (t-NGS) has revolutionized clinical diagnosis allowing multiplexed detection of genomic alterations. This study evaluated the profile of somatic mutations by t-NGS in Mexican patients with non-small cell lung cancer (NSCLC). Materials and methods. Genomic DNA was extracted from 90 lung adenocarcinomas and sequences were generated for a panel of 48 cancer genes. Epidermal Growth Factor Receptor (EGFR) mutations were detected in parallel by quantitative PCR. Results. The mutational profile of NSCLC revealed alterations in 27 genes, where TP53 (47.8%) and EGFR (36.7%) exhibited the highest mutation rates. EGFR Q787 mutations were present in 14 cases (15.6%), 10 cases had exon 19 deletions (11.1%), seven cases had L858R (7.8%). The mutational frequency for genes like EGFR, MET, HNF1A, HER2 and GUSB was different compared to caucasian population. Conclusion. t-NGS improved NSCLC treatments efficacy due to its sensitivity and specificity. A distinct pattern of somatic mutations was found in Mexican population.

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Targeted next generation sequencing identified a high frequency genetic mutated profile in wood smoke exposure-related lung adenocarcinoma patients

Cited by 8 publications

References 29 publications

Clinical Characteristics and Molecular Profiles of Lung Cancer in Ethiopia

Clinical Characteristics and Molecular Profiles of Lung Cancer in Ethiopia

Association between CD47 expression, clinical characteristics and prognosis in patients with advanced non‐small cell lung cancer

Mutational profile by targeted next generation sequencing of non-small cell lung cancer in the Mexican population

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