ABSTRACT
To explore the correlation between epidermal growth factor receptor (EGFR) mutation status and the risk of brain metastasis (BM) in patients with lung adenocarcinoma, the clinical data of 100 patients with pathologically confirmed lung adenocarcinoma and known EGFR mutation status at exon 18, 19, 20, or 21 were analyzed retrospectively. The incidence of BM was similar between patients with wild-type EGFR and those with EGFR mutations (p = 0.48). However, among patients with EGFR mutations, the incidence of BM was significantly higher in patients with mutation at exon 19 than in patients with mutation at other sites (p = 0.007). Besides, among patients with heterochronous BM, 66.7 % had EGFR mutations. Regarding brain-metastasis-free survival (BMFS), patients with EGFR sensitive mutations (mutation at exon 19/21/and dual mutation) had significantly shorter BMFS compared with patients with wild-type EGFR (p = 0.018). For patients treated only with chemotherapy, BM was an unfavorable prognostic factor. Patients with BM had worse overall survival compared with those without BM (p = 0.035). However, in patients with BM and EGFR sensitive mutations, those treated with tyrosine kinase inhibitors (TKIs) had significantly longer overall survival compared with those treated with chemotherapy only (p = 0.0081). In conclusion, among patients with EGFR mutations, those mutated at exon 19 had the highest incidence of BM. Furthermore, patients with EGFR mutations are more likely to develop heterochronous BM. The BMFS was significantly shorter in patients with EGFR sensitive mutations. TKIs improved the survival of patients with lung adenocarcinoma and BM who harbored EGFR sensitive mutations.
Subject(s)
Adenocarcinoma/genetics , Brain Neoplasms/epidemiology , Brain Neoplasms/genetics , ErbB Receptors/genetics , Lung Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Brain Neoplasms/secondary , Disease-Free Survival , Exons , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mutation , Risk FactorsABSTRACT
Thyroid cancer develops from follicular or parafollicular thyroid cells. A higher proportion of anaplastic thyroid cancer has an adverse prognosis. New drugs are being used in clinical treatment. However, for advanced thyroid malignant neoplasm such as anaplastic thyroid carcinoma, the major impediment to successful control of the disease is the absence of effective therapies. Elucidating molecular mechanism of the disease will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In this study, we found that MRTF-A expression was upregulated in metastatic anaplastic thyroid cancer tissues, compared with primary cancer tissues and it promoted metastasis-relevant traits in vitro. miR-206 was negatively associated with metastasis in anaplastic cancer and it degraded MRTF-A by targeting its 3'-UTR in ARO anaplastic thyroid cancer cells. In addition, miR-206 overexpression inhibited invasion and migration and silencing miR-206-promoted migration and invasion in the cells. Important, restoration of MRTF-A could abrogate miR-206-mediated migration and invasion regulation. Thus, we concluded that miR-206 inhibited invasion and metastasis by degrading MRTF-A in anaplastic thyroid cancer.
Subject(s)
MicroRNAs/genetics , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Carcinoma, Anaplastic/pathology , Trans-Activators/genetics , 3' Untranslated Regions , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/metabolism , Neoplasm Metastasis , Thyroid Carcinoma, Anaplastic/metabolism , Trans-Activators/metabolismABSTRACT
OBJECTIVES: To explore the association among Arg(972) insulin receptor substrate-1 (IRS-1), hypertension, insulin resistance, and plasma levels of endothelial nitric oxide synthase (eNOS) and endothelin-1 (ET-1). METHODS: A total of 1030 patients, including 521 healthy controls, 142 patients with both primary hypertension and insulin resistance, 184 patients with primary hypertension but no insulin resistance, and 183 patients with insulin resistance but no hypertension were genotyped for the Arg(972) IRS-1 polymorphism. Serum levels of ET-1 and eNOS were determined by ELISA. Shear stress was applied to human umbilical vein endothelial cells (HUVECs) overexpressing wild type IRS-1 or Arg(972) IRS-1, and the mRNA and secreted protein levels of ET-1 were measured by real-time RT-PCR and ELISA, respectively. RESULTS: There was no significant difference in allelic frequency between patients with and without primary hypertension or insulin resistance, in the hypertensives, heterozygous Arg(972) IRS-1 carriers had significantly higher plasma ET-1 levels and blood pressure (BP) than the homozygous carriers. Although shear stress decreased ET-1 expression in control HUVECs as well as cells transfected with wild type Arg(972) IRS-1, it increased the mRNA dose-dependently and secreted protein levels of ET-1 in cells transfected with Arg(972) IRS-1. CONCLUSIONS: Based on both in-vivo and in-vitro data, we have shown a potential causal association between Arg(972) IRS-1 and elevated plasma ET-1 level in hypertensives, which may account for the aggravated hypertension observed in hypertensives with heterozygous Arg(972) IRS-1. This study for the first time provides insights into the role of Arg(972) IRS-1 in hypertension.
