ABSTRACT
Epithelial-mesenchymal transition (EMT), a pivotal event during cancer progression such as relapse and metastasis, is positively correlated with the stemness potency of tumor cells. Our previous study showed that miR-296-5p attenuated EMT program of hepatocellular carcinoma cells (HCC) through NRG1/ERBB2/ERBB3 signaling. In the present study, we uncovered that miR-296-5p was able to inhibit the stemness potency of HCC by decreasing the number and size of tumorspheres, downregulating the expression of CSC biomarkers and hampering the ability of tumorigenesis in NOD/SCID mice. Brahma-related gene-1 (Brg1), as the target protein of miR-296-5p detected by bioinformatics methods, activates a series of downstream cascades through directly binding to Sall4 promoter and enhancing Sall4 transcription. Importantly, the higher expressions of Brg1 and Sall4 in tumor tissues of HCC patients suggest poorer prognoses after surgical extraction. In conclusion, miR-296-5p exerts an inhibitory effect on stemness potency of HCC cells via Brg1/Sall4 axis.
Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , DNA Helicases/metabolism , Liver Neoplasms/genetics , Liver Neoplasms/pathology , MicroRNAs/metabolism , Neoplastic Stem Cells/metabolism , Nuclear Proteins/metabolism , Transcription Factors/metabolism , Animals , Base Sequence , Cell Line, Tumor , Down-Regulation/genetics , Epithelial Cell Adhesion Molecule/metabolism , Gene Expression Regulation, Neoplastic , Humans , Mice, Inbred NOD , Mice, SCID , MicroRNAs/genetics , Neoplastic Stem Cells/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Signal Transduction , Thy-1 Antigens/metabolismABSTRACT
BACKGROUND: Thymic carcinomas (TCs) and thymic neuroendocrine tumors (TNETs) are aggressive cancers with poor survival outcome and limited investigation. This study is to investigate clinicopathologic features on TC and TNET patients' prognosis of a large cohort. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results database were used to identify a total of 362 TC and TNET patients with documented clinicopathologic features we investigated. The characteristics and overall survival of the TC and TNET patients were studied. RESULTS: Two hundred and forty TC and 122 TNET patients were identified. For the entire cohort of TC and TNET, histologic type (P < 0.001), tumor size (Pâ¯=â¯0.015), Masaoka-Koga stage (Pâ¯=â¯0.008), regional node positive (Pâ¯=â¯0.004), surgery of primary site (P < 0.001), lymph node surgery (P = 0.013), and chemotherapy (P = 0.001) were considered as significant clinicopathologic features that could affect prognosis of TC and TNET patients in univariate analysis. More importantly, histologic type (P < 0.001), regional nodes positive (P = 0.03) and surgery of primary site (P < 0.001) were able to independently predict overall survival of those patients. In addition, for the cohort of TC, we found that regional nodes positive (P = 0.034) and surgery of primary site (P = 0.001) could be independent predictors of TC patients' survival. CONCLUSION: Regional nodes detection is essential for TC and TNET patients. Surgery of primary site is the preferred primary treatment for those patients.
Subject(s)
Lymphatic Metastasis/pathology , Neuroendocrine Tumors/mortality , Thymoma/mortality , Thymus Gland/pathology , Thymus Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Female , Humans , Kaplan-Meier Estimate , Lymph Node Excision/statistics & numerical data , Lymphatic Metastasis/therapy , Male , Middle Aged , Neoplasm Staging , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/therapy , Prognosis , Retrospective Studies , Risk Factors , Thymectomy/statistics & numerical data , Thymoma/diagnosis , Thymoma/pathology , Thymoma/therapy , Thymus Gland/surgery , Thymus Neoplasms/diagnosis , Thymus Neoplasms/pathology , Thymus Neoplasms/therapy , Time Factors , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: Despite the widespread use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced or recurrent non-small cell lung cancer (NSCLC), no biomarkers for predicting the efficacy of EGFR-TKIs in patients with EGFR-sensitive mutations have yet been identified. The purpose of our study was to explore the effect of baseline serum tumor markers in stage IIIB/IV NSCLC patients treated with EGFR-TKIs. METHODS: One hundred and seventy-seven patients with stage IIIB/IV NSCLC who harbored EGFR-sensitive mutations and were treated with EGFR-TKIs were retrospectively reviewed. Their levels of CEA, CYFRA 21-1, NSE and CA199 were measured before treatment with EGFR-TKIs. RESULTS: The response rate for all patients was 54.8%, with a median progression-free survival of 6.6 months and overall survival of 14.8 months. In univariate analyses, patients with CEA levels below the cutoff point (10 ng/ml) had higher RR, better PFS, and better OS than those with CEA levels above 10 ng/mL (RR: 69.2% vs. 43.4%, p= 0.001; mPFS: 7.8 months vs. 5.3 months, p=0.029; mOS: 18.8 months vs. 11.8 months, p=0.000). The baseline serum CEA level was an independent factor for RR (odds ratio [OR] =0.322, p=0.001), PFS (hazard ratio [HR] =1.45, p=0.025), and OS (HR=2.133, p=0.000). CONCLUSION: Our study suggests that baseline serum CEA levels may play a role in predicting the efficacy of EGFR-TKIs in stage IIIB/IV NSCLC patients with EGFR-sensitive mutations who are treated with EGFR-TKIs.
