Epidermal Growth Factor Receptor Gene Mutation in Pleural Lavage Cytology Findings of Primary Lung Adenocarcinoma Cases

Inoue, Takashi; Matsumura, Yuichi; Araki, Osamu; Karube, Yoko; Maeda, Shin; Kobayashi, Satoru; Chida, Masayuki

doi:10.5761/atcs.oa.17-00088

Cited by 4 publications

(6 citation statements)

References 12 publications

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“…The different mutation of epidermal growth factor receptor (EGFR), a receptor belong to the ERBB family, would significantly affect the stage and treatment outcome in LADC which had been well-established in the previous studies [ 8 , 9 ]. The main EGFR mutation types are the L858R expression and Exon 19 in-frame deletion, which are associated with a better prognosis of LADC compared to the LADC with EGFR wild-type [ 10 , 11 , 12 ]. In addition to EGFR, the single nucleotide polymorphism (SNP) of other genes would also correlate to different clinical characteristics and treatment outcome of LADC [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

The Relationship between Long Noncoding RNA H19 Polymorphism and the Epidermal Growth Factor Receptor Phenotypes on the Clinicopathological Characteristics of Lung Adenocarcinoma

Wang

Tsao

et al. 2021

IJERPH

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The aim of the current study is to investigate potential associations among Long Noncoding RNA (LncRNA) H19 single nucleotide polymorphism (SNP) and epidermal growth factor receptor (EGFR) phenotypes on the clinicopathological characteristics of lung adenocarcinoma (LADC). Five loci of LncRNA H19 SNPs (rs217727, rs2107425, rs2839698, rs3024270, and rs3741219) were genotyped by using TaqMan allelic discrimination in 223 LADC patients with wild-type EGFR phenotype and 323 LADC individuals with EGFR mutations. After the statistical analyses, patients with the EGFR mutation were related to a higher distribution frequency of rs217727 SNP CT heterozygote (p = 0.030), and the female population with EGFR mutation demonstrated a higher distribution frequency of rs217727 SNP CT heterozygote (p < 0.001) and rs2107425 CT heterozygote (p = 0.002). In addition, the presence of LncRNA H19 SNP rs217727 T allele (CT + TT) in patients with EGFR wild-type was associated to higher tumor T status (stage III or IV, p = 0.037) and poorer cell differentiation status (poor differentiation, p = 0.012) compared to those EGFR wild-type individuals with LncRNA H19 SNP rs217727 CC allele. Besides, a prominently higher tumor T status was found in subjects with LncRNA H19 SNP rs2107425 T allele (CT + TT) (stage III or IV, p = 0.007) compared to EGFR wild-type LADC individuals with LncRNA CC allele in EGFR wild-type patients. Our findings suggest that the presence of LncRNA H19 SNP rs217727 is related to the EGFR mutation in LADC patients, and the LncRNA H19 SNP rs217727 and rs2107425 are associated with progressed tumor status for LADC patients with EGFR wild-type.

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Section: Introductionmentioning

confidence: 99%

The Relationship between Long Noncoding RNA H19 Polymorphism and the Epidermal Growth Factor Receptor Phenotypes on the Clinicopathological Characteristics of Lung Adenocarcinoma

Wang

Tsao

et al. 2021

IJERPH

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“…Regarding demographic and basic characteristics in the wild-type and mutated EGFR mutation populations, the ratios of female patients, nonsmokers, and those with better cell differentiation were observed in patients with LADC and mutated EGFR phenotypes. Female patients are more prone to lung cancer, including LADC [ 42 ], and EGFR mutations are predictors of favorable responses to target treatments [ 11 , 38 ]. This result implies that other genetic factors cause women to become vulnerable to LADC.…”

Section: Discussionmentioning

confidence: 99%

“…The clinicopathological characteristics between the two EGFR phenotype groups were largely similar and cell differentiation in both groups was typically moderate. The larger numbers of cases with well-differentiated LADC in the mutated EGFR group may have been related to the favorable response to treatment in this population [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

“…The epidermal growth factor receptor (EGFR) is a crucial protein in LADC treatment because it enables EGFR phenotypes and mutations to become prognostic predictors and treatment targets against LADC [ 8 , 9 , 10 ]. Common EGFR mutations include L858R expression and Exon 19 in-frame deletion, which can alter the prognosis and overall survival of individuals with LADC [ 8 , 11 ]. In addition to mutations, interactions between EGFR mutations and other genetic variations influence clinicopathological characteristics and LADC prognoses [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Impact of Aurora Kinase A Polymorphism and Epithelial Growth Factor Receptor Mutations on the Clinicopathological Characteristics of Lung Adenocarcinoma

Yang

Hsieh

Lee

et al. 2020

IJERPH

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Lung adenocarcinoma (LADC) is the most common subtype of lung cancer worldwide and the epidermal growth factor receptor (EGFR) has a great influence on its clinical course, mainly due to the influence of different phenotypes. The Aurora kinase A (AURKA) would influence the progression of several solid malignancies. However, whether the interaction between EGFR phenotypes and AURKA would influence the clinical characteristics of LADC remains unknown. Herein, this study aimed to explore the effects of single-nucleotide polymorphisms (SNPs) of AURKA and EGFR phenotypes on the clinicopathological characteristics of LADC. Four loci of AURKA SNPs (rs1047972, rs2273535, rs6024836, and rs2064863) were genotyped using TaqMan allelic discrimination in 105 wild-type EGFR individuals and 167 LADC patients with EGFR mutations. After the statistical analysis, patients with LADC who had CT heterozygotes of AURKA rs1047972 had a lower risk of EGFR mutations than patients with wild-type homozygotes. Moreover, female and nonsmoking patients who carried the CT genotype of AURKA rs1047972 had a lower risk of EGFR mutation (p = 0.008 and p = 0.004, respectively). Moreover, in patients with EGFR mutations, AURKA SNP rs6024836 G allele (AG + GG) carriers had a lower risk of developing advanced-stage LADC (stage III or IV; odds ratio = 0.423, 95% confidence interval: 0.203–0.879, p = 0.019) than patients with AA homozygotes. Our results suggested that AURKA rs1047972 variants are significantly associated with EGFR mutations among patients with LADC, particularly in female and nonsmoking patients. AURKA variants may contribute to the pathological development of LADC.

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“…Detection of tumor cells in pleural lavage of patients with early stage NSCLC has shown to be associated with shorter overall survival 4 . DNA obtained from pleural lavage material has proven to be appropriate to detect EGFR mutations, even in cases in which tumor cells were not microscopically detected in the lavage 5 . To the best of our knowledge, detection of microRNAs (miRNAs) has not been attempted in this type of material.…”

Section: Introductionmentioning

confidence: 99%

EV-associated miRNAs from pleural lavage as potential diagnostic biomarkers in lung cancer

Roman‐Canal

Moiola

Gatius

et al. 2019

Sci Rep

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Lung cancer is the leading cause of cancer-related deaths among men and women in the world, accounting for the 25% of cancer mortality. Early diagnosis is an unmet clinical issue. In this work, we focused to develop a novel approach to identify highly sensitive and specific biomarkers by investigating the use of extracellular vesicles (EVs) isolated from the pleural lavage, a proximal fluid in lung cancer patients, as a source of potential biomarkers. We isolated EVs by ultracentrifuge method from 25 control pleural fluids and 21 pleural lavages from lung cancer patients. Analysis of the expression of EV-associated miRNAs was performed using Taqman OpenArray technology through which we could detect 288 out of the 754 miRNAs that were contained in the OpenArray. The differential expression analysis yielded a list of 14 miRNAs that were significantly dysregulated (adj. p-value < 0.05 and logFC lower or higher than 3). Using Machine Learning approach we discovered the lung cancer diagnostic biomarkers; miRNA-1-3p, miRNA-144-5p and miRNA-150-5p were found to be the best by accuracy. Accordance with our finding, these miRNAs have been related to cancer processes in previous studies. This results opens the avenue to the use of EV-associated miRNA of pleural fluids and lavages as an untapped source of biomarkers, and specifically, identifies miRNA-1-3p, miRNA-144-5p and miRNA 150-5p as promising biomarkers of lung cancer diagnosis.

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Epidermal Growth Factor Receptor Gene Mutation in Pleural Lavage Cytology Findings of Primary Lung Adenocarcinoma Cases

Cited by 4 publications

References 12 publications

The Relationship between Long Noncoding RNA H19 Polymorphism and the Epidermal Growth Factor Receptor Phenotypes on the Clinicopathological Characteristics of Lung Adenocarcinoma

The Relationship between Long Noncoding RNA H19 Polymorphism and the Epidermal Growth Factor Receptor Phenotypes on the Clinicopathological Characteristics of Lung Adenocarcinoma

Impact of Aurora Kinase A Polymorphism and Epithelial Growth Factor Receptor Mutations on the Clinicopathological Characteristics of Lung Adenocarcinoma

EV-associated miRNAs from pleural lavage as potential diagnostic biomarkers in lung cancer

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