Correlations between EGFR gene polymorphisms and pleural metastasis of lung adenocarcinoma

Abstract

Proliferation, growth, and differentiation of cells are strictly controlled by the signal system of epidermal growth factor receptor (EGFR). If any link of the EGFR signals system is interfered with or damaged, the proliferation, growth, and differentiation of cells would become uncontrolled. EGFR is overexpressed in a variety of malignant tumors, such as non-small-cell lung cancer, colorectal cancer and breast cancer. Results of the study have proved that EGFR overexpression is closely associated with mutations and variants of the EGFR genes, whose mutations and variants are associated with occurrence, metastasis, and prognosis of different types of tumors, including lung cancer. This study is aimed at investigating whether the polymorphisms of CA simple sequence repeat in intron 1 (CA-SSR1), -216G/T, and R497K in the EGFR are able to induce EGFR activation and whether overexpression is associated with pleural metastasis of lung adenocarcinoma. A total of 432 lung adenocarcinoma patients with pleural metastasis (metastasis group) and 424 patients with lung adenocarcinoma but without pleural metastasis (nonmetastasis group) were enrolled in this study. For all patients, the CA-SSR1 genotypes were determined by capillary electrophoresis, polymerase chain reaction amplification, and direct DNA sequencing, and the R497K and -216G/T genotypes were determined by polymerase chain reaction amplification and direct DNA sequencing. EGFR expression was evaluated by immunohistochemical staining in primary tumor tissues with different -216G/T, R497K, and CA-SSR1 genotypes. Our results showed significant differences between pleural metastasis and nonmetastasis groups in the genotype and allele distribution of -216G/T, R497K, and CA-SSR1 polymorphisms of the EGFR gene. The -216T allele, Arg allele, and shorter CA-SSR1 (<17) had significantly increased risks of pleural metastasis compared with the -216G allele, Lys allele, and longer CA-SSR1 (≥17), respectively. The expression of EGFR was higher in patients with genotypes of -216T/T or -216G/T, Arg/Arg or Arg/Lys, and shorter CA-SSR1 (<17) than that in patients with genotypes of -216G/G, Lys/Lys, and longer CA-SSR1 (≥17), respectively. These results indicate that -216G/T, R497K, and CA-SSR1 polymorphisms are associated with the risk of pleural metastasis of lung adenocarcinoma, which may be related to the overexpression of EGFR protein induced by -216G/T, R497K, and CA-SSR1 polymorphisms.

Epidermal Growth Factor Receptor Gene in Non-Small-Cell Lung Cancer: The Importance of Promoter Polymorphism Investigation

“…Namely, as the process of cell proliferation and differentiation is strictly related to EGFR, tumor metastasis should be affected by variations in EGFR . In line with the expectations, significant differences in genotype and allele frequencies of the -216G/T polymorphism between the patient group with the pleural metastasis in comparison with the nonmetastasis group have been observed [ 100 ]. Based on these findings, the authors have concluded that the polymorphism in exon 13 of the EGFR gene might be one of the molecular mechanisms of pleural metastasis of lung cancer.…”

Survival time following resection of intracranial metastases from NSCLC-development and validation of a novel nomogram

“…Second, due to higher incidences of mutant genes (EGFR, ALK, ROS1, etc.) in ADC [ 26 ], the use of new targeted agents will enhance the response rates and prolong OS. We did not investigate the other rare types of NSCLC.…”

Intrapleural targeted therapies (anti-VEGF and anti-EGFR) in the model of malignant pleural effusion

“…EGFR, a tyrosine kinase receptor considered to be oncogenic, is responsible for growth, survival, proliferation and differentiation of several cell types. Its activation occurs either through EGF or, in cases of mutations, by the activation of the tyrosine-receptor kinase by other mediators initiating multiple cascades of intracellular events [ 8 , 20 , 27 ]. When altered, either by hyperexpression, amplification or mutations, it induces uncontrolled growth or malignant phenotype, since this pathway physiologically regulates aspects of cell proliferation and survival [ 1 , 20 , 27 ].…”