Low expression of long non-coding RNA GAS5 is associated with poor prognosis of patients with thyroid cancer.

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.

PTEN/PI3K/AKT protein expression is related to clinicopathological features and prognosis in breast cancer with axillary lymph node metastases.

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.

A network meta-analysis for toxicity of eight chemotherapy regimens in the treatment of metastatic/advanced breast cancer.

OBJECTIVE: To compare the incidence of toxicity of 8 different chemotherapy regimens, including doxorubicin + paclitaxel, doxorubicin, capecitabine, CMF (cyclophosphamide + methotrexate + 5-fluorouracil), FAC (fluorouracil + doxorubicin + cyclophosphamide), doxorubicin + docetaxel, doxorubicin + cyclophosphamide and paclitaxel in the treatment of metastatic/advanced breast cancer. RESULTS: This network meta-analysis included 8 randomized controlled trials (RCTs). The findings revealed that, with regard to capecitabine alone regimen exhibited higher incidence of nausea/vomiting than doxorubicin + paclitaxel regimen, doxorubicin alone regimen and paclitaxel alone regimen in the treatment of patients with metastatic/advanced breast cancer (OR = 32.48, 95% CI = 1.65~2340.57; OR = 22.75, 95% CI = 1.03~1923.52; OR = 59.63, 95% CI = 2.22~5664.88, respectively). Furthermore, doxorubicin + cyclophosphamide regimen had lower incidence of febrile neutropenia than doxorubicin + docetaxel (OR = 0.17, 95% CI = 0.03~0.96). No significant difference in the incidence of stomatitis was observed among eight chemotherapy regimens. MATERIALS AND METHODS: We initially searched PubMed, Cochrane Library and Embase databases from the founding of these databases to January 2016. Eligible studies investigating the 8 different chemotherapy regimens for treatment of metastatic/advanced breast cancer were included for direct and indirect comparison. The odds ratio (OR) and surface under the cumulative ranking curves (SUCRA) value of the incidence of toxicity among eight chemotherapy regimens were analyzed. CONCLUSIONS: Capecitabine alone regimen and doxorubicin + docetaxel regimen may have a more frequent toxicity in the treatment of metastatic/advanced breast cancer.

Long non-coding RNA ANRIL promotes the invasion and metastasis of thyroid cancer cells through TGF-ß/Smad signaling pathway.

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.

Roles of microRNA-124a and microRNA-30d in breast cancer patients with type 2 diabetes mellitus.

The aim of the study is to explore roles of microRNA (miR)-124a and miR-30d in breast cancer (BC) patients with type 2 diabetes mellitus (T2DM). A total of 144 cases of confirmed diagnosed BC with T2DM, T2DM, BC, or healthy people were enrolled. Among them, BC patients with T2DM were regarded as the experiment group (n = 36), patients with T2DM as the Dm group (n = 36), patients with BC as the Bc group (n = 36), and healthy subjects as the healthy group (n = 36). The fasting insulin resistance index, glycosylated hemoglobin, and estradiol were measured. MiR-124a and miR-30d expressions were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The insulin resistance index was significantly higher in the experiment group compared to the other three groups (all P < 0.05). The glycated hemoglobin was in a normal range in the Bc group and healthy group, but was higher in the experiment group and the Bc group compared to that in the healthy group (both P < 0.05). The serum estradiol level was obviously higher in the Bc group compared with that in the Dm group and the experiment group (both P < 0.05). The expressions of miR-124a and miR-30d were positively correlated with insulin resistance index, BMI and glycosylated hemoglobin (miR-124a r = 0.659, r = 0.785, and r = 0.862; miR-30d r = 0.742, r = 0.805, r = 0.765; all P < 0.001). Insulin resistance index was an independent factor for expressions of miR124-a and miR-30d. MiR-124a and miR-30d were correlated with insulin resistance and development of BC with T2DM. Although the mechanism is not clear, miR-124a and miR-30d potentially may be used as therapeutic targets and prognostic markers for BC patients with T2DM.