ABSTRACT
The study aims to investigate the role of long non-coding RNA (lncRNA) GAS5 in the diagnosis and prognosis of patients suffering from thyroid cancer (TC). A total of 212 patients with TC and 61 patients with benign thyroid tumor were enrolled in the study. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the lncRNA GAS5 expression in TC and benign tumor tissues. All TC patients were categorized into high-risk and low-risk groups according to the MACIS, AGES and AMES prognostic scoring system. A 5-year follow-up was conducted in order to determine the disease free survival (DFS) rates and overall survival (OS) rates. The associations between lncRNA GAS5 expression and prognosis of TC patients were analyzed by The Kaplan-Meier survival curves and the Cox regression models. There was a decrease in the lncRNA GAS5 expression in TC tissues in comparison to benign tumor tissues. Expression of lncRNA GAS5 showed significant association with tumor node metastasis (TNM) staging, lymph node metastasis and the multiple cancer foci of TC. AMES high-risk patients showed a decreased expression of lncRNA GAS5 expression than the AMES low-risk patients. The AGES and MACIS high-risk patients showed lower lncRNA GAS5 expression than low-risk patients. The survival rate of TC patients with high lncRNA GAS5 expression was higher than that of TC patients with low lncRNA GAS5 expression during the DFS and OS periods. Cox regression analysis indicated that lncRNA GAS5 expression, TNM staging, lymph node metastasis and multiple cancer foci were independent risk factors for poor prognosis in TC patients. LncRNA GAS5 may be closely related to the diagnosis and prognosis of TC.
Subject(s)
Gene Expression Regulation, Neoplastic , RNA, Long Noncoding/genetics , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/genetics , Adult , Case-Control Studies , Disease-Free Survival , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Lymphatic Metastasis , Male , Middle Aged , Prognosis , Proportional Hazards Models , RNA, Long Noncoding/metabolism , Real-Time Polymerase Chain Reaction , Survival Rate , Young AdultABSTRACT
We explored the relations between PTEN/PI3K/AKT expression and clinicopathological characteristics and prognosis in breast cancer patients with and without axillary lymph node metastasis (LNM). Tissues and follow-up data from 142 patients with (LNM group) and 154 without (non-LNM group) metastases were collected. Expression of PTEN/PI3K/AKT was detected using immunohistochemistry staining. With axillary LNM, the positive rate of PTEN was reduced, whereas that of PI3K and AKT was increased. Expression of AKT was negatively correlated with PTEN expression but positively correlated with PI3K expression. Apparent correlations were detected between AKT and axillary LNM with a tumor size of 2 cm or less; between PTEN, PI3K, and AKT and axillary LNM in stage T1 or T2 breast cancer and invasive carcinoma of a nonspecial type; and between PTEN and AKT and axillary LNM of histologic grade I or II tumors and non-triple-negative breast cancer (all P<.05). In the LNM group, the 5-year survival rate of patients with PTEN-positive tumors was higher than that of patients with PTEN-negative lesions; whereas in the non-LNM group, the 5-year survival rate of patients with AKT-positive tumors was lower than that of patients with AKT-negative lesions (both P<.05). Cox regression analysis showed that PTEN expression was an independent prognostic factor for patients with LNM; AKT expression, tumor diameter, pathologic grade, and pathologic type were independent prognostic factors for patients without LNM. In conclusion, TEN/PI3K/AKT proteins are related to the clinicopathological features and prognosis of breast cancer with axillary LNM.
Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/enzymology , Carcinoma/enzymology , Lymph Nodes/pathology , PTEN Phosphohydrolase/analysis , Phosphatidylinositol 3-Kinase/analysis , Proto-Oncogene Proteins c-akt/analysis , Adult , Aged , Biopsy , Breast Neoplasms/pathology , Breast Neoplasms/therapy , Carcinoma/secondary , Carcinoma/therapy , Case-Control Studies , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lymphatic Metastasis , Middle Aged , Neoplasm Grading , Neoplasm Staging , Proportional Hazards Models , Tumor Burden , Young AdultABSTRACT
OBJECTIVE: To investigate the effect of antisense non-coding RNA in the INK4 locus (ANRIL) on invasion and metastasis of thyroid cancer (TC). RESULTS: ANRIL expression was significantly up-regulated in TC tissues and cells (P < 0.001), and ANRIL expression was significantly different regarding histological grade and LNM (both P < 0.01). The siRNA-mediated ANRIL silencing inhibits proliferation, invasion, and metastasis of TPC-1 and SW579 cells, and lung metastasis, which can be reversed by TGF-ß1 siRNA. The mRNA levels of p15INK4b, p14ARF and p16INK4a in TPC-1 and SW579 cells increased significantly after silencing ANRIL (all P < 0.001), and TGF-ß1 siRNA could reverse the ANRIL siRNA induced increase of p15INK4b; expressions of TGF-ß1 and p-Smad2/3 were increased after silencing ANRIL (both P < 0.05). MATERIALS AND METHODS: TC and adjacent normal tissues were collected from 105 TC patients. LncRNA ANRIL expressions were detected by qRT-PCR. The siRNA ANRIL and siRNA TGF-ß1 were constructed for TPC-1 and SW579 cell line transfection: si-ANRIL group, si-TGF-ß1 group, si-ANRIL + si-TGF-ß1 group, negative control group and blank group. Effects of ANRIL silencing on proliferation, invasion and metastasis of TC cells was detected by MTT assay, Transwell assay and tail vein injection of nude mice in vitro and in vivo. TGF-ß1 and p-Smad2/3 expressions in TGF-ß/Smad signaling pathway were detected by western blot. CONCLUSIONS: ANRIL may reduce p15INK4B expression through inhibiting TGF-ß/Smad signaling pathway, promoting invasion and metastasis of TC cells, and the silencing of ANRIL inhibits the invasion and metastasis of TPC-1 cells.
