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Correlation of E-cadherin gene polymorphisms and epidermal growth factor receptor mutation in lung adenocarcinoma.

ABSTRACT: Epithelial-mesenchymal transition (EMT) was recently discovered related to the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients and cell lines. In this study, we aimed to explore the association among the E-cadherin gene (CDH1) genetic variants, TK-domain mutations of EGFR, and clinicopathologic characteristics in patients with lung adenocarcinoma. A total of 280 patients with lung adenocarcinoma were recruited between years 2012 and 2015. All subjects underwent the analysis of CDH1 genetic variants (rs16260 and rs9929218) by real-time polymerase chain reaction (PCR) genotyping. The results showed that CA and CA + AA genotypes of CDH1 single nucleotide polymorphism (SNP) rs16260 were significantly reverse associated with EGFR mutation type (Adjusted odds ratio (AOR) = 0.43, 95% CI = 0.20-0.92 and AOR = 0.46, 95% CI = 0.22-0.96, respectively) in female lung adenocarcinoma patients. Moreover, the significantly reverse associations between CA and CA + AA genotypes of CDH1 rs16260 and EGFR hotspot mutations, namely L858R mutation and exon 19 in-frame deletion, were also demonstrated among female patients. Besides, CA + AA genotype of CDH1 rs16260 was noted significantly reverse associated with the tumor sizes (OR = 0.31, 95% CI = 0.12-0.80; p = 0.012). In conclusion, our results suggested that CDH1 variants are significantly reverse associated with mutation of EGFR tyrosine kinase, especially among the female patients with lung adenocarcinoma. The CDH1 variants might contribute to pathological development in lung adenocarcinoma.

SUBMITTER: Huang CY

PROVIDER: S-EPMC6036082 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Correlation of E-cadherin gene polymorphisms and epidermal growth factor receptor mutation in lung adenocarcinoma.

Huang Chun-Yao CY Hsieh Ming-Ju MJ Liu Tu-Chen TC Chiang Whei-Ling WL Liu Ming-Che MC Yang Shun-Fa SF Tsao Thomas Chang-Yao TC

International journal of medical sciences 20180522 8

Epithelial-mesenchymal transition (EMT) was recently discovered related to the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients and cell lines. In this study, we aimed to explore the association among the E-cadherin gene (<i>CDH1</i>) genetic variants, TK-domain mutations of <i>EGFR</i>, and clinicopathologic characteristics in patients with lung adenocarcinoma. A total of 280 patients with lung adenocarcinoma were recruited between years 2012 ...[more]

PMID: 30008585

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Project description:Purpose To retrospectively identify the relationship between epidermal growth factor receptor (EGFR) mutation status, predominant histologic subtype, and computed tomographic (CT) characteristics in surgically resected lung adenocarcinomas in a cohort of Asian patients. materials and Methods This study was approved by the institutional review board, with waiver of informed consent. Preoperative chest CT findings were retrospectively evaluated in 385 surgically resected lung adenocarcinomas. A total of 30 CT descriptors were assessed. EGFR mutations at exons 18-21 were determined by using the amplification refractory mutation system. Multiple logistic regression analyses were performed to identify independent factors of harboring EGFR mutation status. The final model was selected by using the backward elimination method, and two areas under the receiver operating characteristic curve (ROC) were compared with the nonparametric approach of DeLong, DeLong, and Clarke-Pearson. Results EGFR mutations were found in 168 (43.6%) of 385 patients. Mutations were found more frequently in (a) female patients (P < .001); (b)those who had never smoked (P < .001); (c)those with lepidic predominant adenocarcinomas (P = .001) or intermediate pathologic grade (P < .001); (e) smaller tumors (P < .001); (f)tumors with spiculation (P = .019), ground-glass opacity (GGO) or mixed GGO (P < .001), air bronchogram (P = .006), bubblelike lucency (P < .001), vascular convergence (P = .024), thickened adjacent bronchovascular bundles (P = .027), or pleural retraction (P < .001); and (g) tumors without pleural attachment (P = .004), a well-defined margin (P = .010), marked heterogeneous enhancement (P = .001), severe peripheral emphysema (P = .002), severe peripheral fibrosis (P = .013), or lymphadenopathy (P = .028). The most important and significantly independent prognostic factors of harboring EGFR-activating mutation for the model with both clinical variables and CT features were those who had never smoked and those with smaller tumors, bubblelike lucency, homogeneous enhancement, or pleural retraction when adjusting for histologic subtype, pathologic grade, or thickened adjacent bronchovascular bundles. ROC curve analysis showed that use of clinical variables combined with CT features (area under the ROC curve = 0.778) was superior to use of clinical variables alone (area under the ROC curve = 0.690). Conclusion CT imaging features of lung adenocarcinomas in combination with clinical variables can be used to prognosticate EGFR mutation status better than use of clinical variables alone. (©) RSNA, 2016 Online supplemental material is available for this article.

Project description:BackgroundThe nuclear translocation of epidermal growth factor receptor (EGFR) has been considered to play a role in carcinogenesis. However, the relevance of differentially located EGFR proteins in lung cancer remains unclear.MethodsWe examined 161 patients with primary lung adenocarcinoma to detect EGFR expression in lung cancer cells using immunohistochemistry and determined the correlations of EGFR expression with clinical characteristics, EGFR mutations, and survival time. Moreover, we graded complete membranous staining with strong intensity as high membranous EGFR (mEGFR) expression, and nuclear EGFR staining with strong intensity as high nuclear (nEGFR) expression.ResultsThe prevalence of high mEGFR and nEGFR expression in lung adenocarcinoma was 42.86 and 39.13%, respectively. After multivariate analyses, high mEGFR expression was associated with a significantly reduced mortality risk in older patients, those with a history of smoking, and those without brain metastasis (hazard ratio[95% confidential interval], HR[95% CI] = 0.55[0.32~ 0.92]; 0.51[0.26~ 0.98] and 0.56[0.33~ 0.94], in overall survival, respectively). An association between high nEGFR expression and early recurrence was observed in patients with metastasis (HR[95% CI] =1.68[1.05~ 2.68], in progression-free survival). Notably, patients with low mEGFR and low nEGFR expression had the lowest survival rate in cases without brain metastasis (p = 0.018) and with a history of smoking (p = 0.062) and total EGFR (any high mEGFR or nEGFR) expression indicated a more favorable response to platinum-based chemotherapy regardless of EGFR mutations (HR[95% CI] =0.33[0.12-0.92]; adjusted HR[95% CI] = 0.36[0.13~ 1.02] with the use of tyrosine kinase inhibitor).ConclusionsEGFR proteins at different cellular locations in lung adenocarcinoma might influence the biology of cancer cells and are an independent indicator of more favorable prognosis and treatment response.

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Correlation of E-cadherin gene polymorphisms and epidermal growth factor receptor mutation in lung adenocarcinoma.

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Correlation of E-cadherin gene polymorphisms and epidermal growth factor receptor mutation in lung adenocarcinoma.

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