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At least 127 records · Page 7

Percutaneous Cryoablation of Stage T1b Renal Cell Carcinoma: Safety, Technical Results, and Clinical Outcomes

Purpose: The use of percutaneous cryoablation for T1b (4.1–7.0 cm) renal cell carcinoma, has not yet been widely adopted. The purpose of this study was to describe our experience in the cryoablation of stage T1b tumors with an emphasis on safety, technical results, and clinical outcomes. Materials and Methods: A retrospective review of hospital records identified 37 patients who underwent cryoablation for T1b lesions from 2008 to 2018. Patient demographics, comorbidities, tumor characteristics, technical parameters, and outcomes were recorded and analyzed. Recurrence-free, overall, and cancer-specific survival rates were estimated using the Kaplan–Meier method. Results: Thirty-seven patients (22 males, 15 females; mean age 66.5 ± 11.3) with 37 T1b tumors (mean diameter 47.3 ± 6.3 mm) were included. A median of 3 probes were used (range: 1–7). Angio-embolization was used in 3/37 (8.1%) and 2/37 patients (5.4%) required hydrodissection. The mean number of total cryoablation procedures for each patient was 1.5 (median 1; range: 1–4). Technical success was achieved in 88.2% of patients. Recurrence-free survival was 96.5%, 86.1%, and 62.6% at 1, 2, and 3 years respectively. Cancer-specific survival was 100% at 1, 2, and 3 years respectively. Overall survival was 96.7%, 91.8%, and 77.6% at 1, 2, and 3 years respectively. Complications classified as CIRSE grade 2 or higher occurred in 6/37 (16.2%) patients. Conclusion: T1b cryoablation is associated with high rates of technical success, excellent cancer-specific survival, and an acceptable safety profile. Level of Evidence: Level 4, Case Series.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Restenosis Rates After Drug-Eluting Stent Treatment for Stenotic Small-Diameter Renal Arteries

Purpose: To determine primary rates in small-diameter renal arteries, including complex bifurcation lesions, treated with drug-eluting stents (DES) in patients with atherosclerotic renal artery stenosis. Materials and Methods: This is a retrospective single-institution study. A total of 37 patients with 39 stented renal arteries were included. Patient and procedural data were obtained from the electronic medical record. Survival free from restenosis was estimated using the Kaplan–Meier method with patients stratified into two groups based on renal artery diameters (≤ 3.5 mm or > 3.5 mm). Univariate Cox proportional models were used to estimate hazard ratios associated with clinical and angiographic variables. Results: Average renal artery diameter at time of treatment was 3.4 mm ± 0.4 mm. The median survival free from restenosis was 992 days, with 11 out of 37 (29.7%) developing an in-stent restenosis. Renal arteries < 3.5 mm in diameter had similar patency rates as renal arteries > 3.5 mm (P = 0.33). The 1-, 2-, and 5-year patency rates were 71%, 63%, and 38%, respectively. History of stroke was the only comorbidity to portend a significantly greater rate of restenosis (hazard ratio 3.77; 95%CI, 1.05–13.6; P = 0.04). Medications did not statistically alter the risk of restenosis. Conclusion: Revascularization of renal arteries with DES achieved similar primary patency rates irrespective of renal artery diameter. Stent configuration was not associated with time to renal replacement therapy or all-cause mortality. Level of Evidence: Level 3, Cohort Study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Risk-Aware Framework Development for Disruption Prediction: Alcator C-Mod and DIII-D Survival Analysis

Abstract Survival regression models can achieve longer warning times at similar receiver operating characteristic performance than previously investigated models. Survival regression models are also shown to predict the time until a disruption will occur with lower error than other predictors. Time-to-event predictions from time-series data can be obtained with a survival analysis statistical framework, and there have been many tools developed for this task which we aim to apply to disruption prediction. Using the open-source Auton-Survival package we have implemented disruption predictors with the survival regression models Cox Proportional Hazards, Deep Cox Proportional Hazards, and Deep Survival Machines. To compare with previous work, we also include predictors using a Random Forest binary classifier, and a conditional Kaplan-Meier formalism. We benchmarked the performance of these five predictors using experimental data from the Alcator C-Mod and DIII-D tokamaks by simulating alarms on each individual shot. We find that developing machine-relevant metrics to evaluate models is an important area for future work. While this study finds cases where disruptive conditions are not predicted, there are instances where the desired outcome is produced. Giving the plasma control system the expected time-to-disruption will allow it to determine the optimal actuator response in real time to minimize risk of damage to the device.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Improving hydroturbine pressures to enhance salmon passage survival and recovery

This paper provides an overview of turbine pressure data collection and barotrauma studies relative to fish passage through large Kaplan turbines and how this information may be applied to safer fish passage through turbines. The specific objectives are to 1) discuss turbine pressures defined by Sensor Fish releases; 2) discuss what has been learned about pressure effects on fish and the factors influencing barotrauma associated with simulated turbine passage; 3) elucidate data gaps associated with fish behavior and passage that influence barotrauma during turbine passage; 4) discuss how the results of these studies have led to turbine design criteria for safer fish passage; and 5) relate this information to salmon recovery efforts and safer fish passage for Atlantic and Pacific salmonids.

42 ENGINEERING↗

Postoperative weight loss followed by radical cystectomy predicts poor prognosis in patients with muscle-invasive bladder cancer

We aimed to investigate the impact of postoperative weight loss following radical cystectomy (RC) on patients’ prognoses. RC and urinary diversion were performed in 512 consecutive patients with muscle-invasive bladder cancer at our hospitals between May 1996 and July 2018. Demographic clinical information, pre- and postoperative serum albumin, hemoglobin, and weight were evaluated retrospectively at 1 month. We also evaluated the association of weight loss with complications and overall survival (OS) as estimated using the Kaplan–Meier method and compared using the log-rank test. Risk factors for poor OS were determined by Inverse Probability of Treatment Weighted (IPTW)-adjusted Cox regression analysis. In 385 patients who met the study search criteria, median postoperative weight loss from baseline at 1 week and 1 month was 1.1 (− 1.8%) and 3.2 (− 5.4%) kg, respectively. Patients with significant weight loss (defined as ≥ 7.5% at 1 month) had higher-grade complications within 1 month and had significantly shorter OS than those with weight loss of < 7.5%. Type of urinary diversion, loss of serum albumin, and loss of hemoglobin were not significantly associated with weight loss. IPTW-adjusted Cox regression analysis showed that such significant weight loss was an independent risk factor for poor OS. Weight loss followed by radical cystectomy was significantly associated with poor prognosis in patients with muscle-invasive bladder cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The correlation between the incidence of adverse events and progression-free survival in patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC)

Clinical practice shows significant differences in treatment outcomes across patients treated with cabozantinib for metastatic renal cell carcinoma (mRCC). It is not known whether cabozantinib-induced adverse events are predictive factors of survival as in case of drugs such as sunitinib or axitinib. The study participants were 30 adult patients with mRCC treated with cabozantinib as a second- or further line setting. All adverse events were evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Progression-free survival (PFS) values were calculated by taking the beginning of cabozantinib treatment as the start date and either disease progression or death as the end date. PFS were estimated using the Kaplan–Meier method, and compared using the log-rank test. We identified independent PFS predictors using multiple Cox proportional hazards models and reported hazard ratios (HR) with 95% confidence intervals. The median observation time cabozantinib treatment was 7.5 months, with a range of 2–15 months. During that time, 11 (37%) of the patients had mRCC progression. Median PFS on cabozantinib was not reached, and lower quartile was 6 months. All patients developed at least one adverse event in the course of cabozantinib therapy. Hypertension, hypothyroidism and HFS were observed most frequently, in about two-thirds of the patients. The co-incidence of multiple adverse events was common. Hypertension, hypothyroidism, diarrhea and liver toxicity were significantly associated with longer PFS values. Patients with three or more side effects had significantly longer PFS than those with two or fewer. Even though this study was conducted in a small patient sample and the observation time was relatively short our results confirm the predictive value of the incidence of adverse events during cabozantinib treatment in mRCC patients. To the best of our knowledge, this is the first study of this kind conducted in this group of patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Real-world outcomes in patients with unresected stage III non-small cell lung cancer

This study examined real-world clinical outcomes such as progression-free survival (PFS), time to metastasis (TTM), overall survival (OS), and health-related quality of life (HRQOL) in patients with unresected stage III non-small cell lung cancer (NSCLC) treated in the community setting. A retrospective review of medical records extracted from 10 US community oncology practices was conducted. Eligible patients were adults diagnosed with stage III NSCLC from 1/1/2011 to 3/1/2016 without evidence of surgical resection within 6 months after stage III NSCLC diagnosis (index date). PFS, OS, and TTM were assessed from the index date, and were analyzed using Kaplan–Meier and Cox regression analyses. HRQOL was assessed for a subset of patients using a patient-reported measure, the 86-item Patient Care Monitor (PCM). Linear mixed models (LMM) were used to assess the impact of patient characteristics and change in PCM scores associated with progression. Among the sample of 478 patients, median PFS (95% confidence interval) was 10 months (9–11), median OS was 20 months (17–22), and median TTM was 30 months (23–45). Most patients (58.2%) experienced disease progression, which the LMM showed to be associated with significant worsening of physical symptoms and psychological states (p < 0.001). This study documented PFS and OS consistent with published literature. The majority of patients experienced disease progression, which was associated with worsening of HRQOL. These findings highlighted the need for better therapeutic options in patients with unresected stage III NSCLC with potential to improve patient outcomes and HRQOL.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Factors that impact the outcomes in testicular germ cell tumors in low–middle-income countries

Germ cell tumors (GCTs) are one of the most common tumors in adolescents and young adults. There is paucity of data on GCT from low–middle-income countries (LMIC). The present study was conducted to assess the demographic features, clinical manifestations, pathology, and outcomes of GCT patients treated at our center. Patients with testicular GCT above the age of 18 years, treated at our center from 2001 to 2015 were included in the study. Data were extracted retrospectively from the case records. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan–Meier method and the variables were compared using the log-rank test. The study included 421 patients among whom 128 (30%) had a histological diagnosis of seminoma and 293 (70%) had non-seminomatous germ cell tumor (NSGCT). Metastatic disease at presentation was observed in 83/128 (65%) with seminoma and 254/293 (87%) with NSGCT. According to the International Germ Cell Cancer Collaborative Group (IGCCCG) risk stratification for metastatic disease, good- and intermediate-risk seminoma were observed in 55/83 (66%) and 28/83 (34%) patients, respectively, and good-, intermediate-, and poor-risk NSGCT were observed in 82/254 (32%), 76/254 (30%), and 96/254 (38%) patients, respectively. The median follow-up was 32.3 months (range 0.03–200 months). The 3-year OS for the entire cohort was 80.3%. The 3-year OS for seminoma was 91.4%, and for NSGCT was 75.3%. Factors significantly associated with inferior EFS and OS on multivariate analysis included poor performance status, scrotal orchidectomy, carboplatin-based regimen, NSGCT histology, and treatment default. Patients with testicular GCT in India present in an advanced stage and higher IGCCCG risk compared to Western data. Factors unique to LMIC like treatment default, bulky disease, dose compromise, and scrotal orchidectomy have a negative impact on the outcome.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Outcomes in patients ≥ 80 years with a diagnosis of a hepatopancreaticobiliary (HPB) malignancy

Older patients are underrepresented in oncological clinical trials. The incidence of hepatopancreaticobiliary (HPB) malignancies is higher in older patients, but data on outcomes are lacking. This study assessed patient outcomes in those < 80 and ≥ 80 years with a HPB malignancy seen at a tertiary referral centre, The Christie NHS Foundation Trust. Data on patients with a HPB malignancy were collected retrospectively between 2012 and 2017 via on-line case-note review. Survival was calculated using the Kaplan–Meier method and prognostic factors using log-rank analysis. Of 1421 patients, 10% were ≥ 80 years. Of patients < 80 and ≥ 80 years, 56% and 57% had pancreas cancer, 39% and 36% biliary tract cancer, and 5% and 7% had hepatocellular carcinoma, respectively. Amongst patients ≥ 80 years, 75% had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Patients ≥ 80 years had higher rates of comorbidity; 28% received systemic anti-cancer therapy (SACT), compared with 62% of patients < 80 years. Best supportive care (BSC) was instituted in 44% of older patients, compared with 13% in those < 80 years. Of patients ≥ 80 years who received SACT, 82% received monotherapy. Median overall survival (OS) for patients receiving palliative SACT was 10.07 months (95% CI 8.89–11.08) and 10.10 months (95% CI 6.30–12.30) in patients < 80 and ≥ 80 years, respectively, p 0.41; ECOG PS (p < 0.001) was prognostic for OS in older patients but Adult Comorbidity Evaluation-27 comorbidity score (p = 0.07, when comparing groups of ACE score ≤ 1 and > 1) was not. Baseline factors were similar in both age cohorts, but more comorbidities were present in older patients. Older patients were less likely to receive SACT, but when they did, they had an equivalent benefit in OS to younger patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Prognostic value of left ventricular dyssynchrony evaluated by gated myocardial perfusion imaging in patients with chronic kidney disease and normal perfusion defect scores

Background: This study aimed to investigate whether indices of left ventricular (LV) dyssynchrony by gated myocardial perfusion SPECT (GMPS) could be useful to predict prognosis in chronic kidney disease (CKD) patients with normal perfusion defect scores. Methods: One hundred and sixty-seven CKD patients with normal perfusion defect scores on adenosine-stress {sup 201}Tl GMPS and no previous history of overt heart diseases were enrolled. Phase standard deviation (PSD) and bandwidth (BW) were automatically calculated from GMPS. The major adverse cardiac events (MACEs) for a mean of 560 days were defined as sudden cardiac death, fatal arrhythmias, and acute coronary syndrome requiring urgent coronary revascularization. Patients were divided into two groups according to the presence or absence of MACEs. Results: The MACEs occurred in 12 patients (7.1%). Patients who experienced MACEs showed significantly higher PSD and wider BW than those who did not. In the Kaplan-Meier event-free survival analysis, cardiac event rate was significantly higher in the high-PSD and wide-BW group (n = 81) than in the low-PSD and narrow-BW group (n = 71) (P = .002). The multivariate regression analysis revealed that the PSD was associated with MACEs (odds ratio 1.33, 95% confidence interval 1.05-1.69, P = .01). Conclusion: The LV dyssynchrony indices from GMPS may be novel prognostic predictors in CKD patients with normal perfusion defect scores.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Overexpressed KDM5B is associated with the progression of glioma and promotes glioma cell growth via downregulating p21

Highlights: • KDM5B is overexpressed in glioma samples. • KDM5B stimulated proliferation of glioma cells. • Inhibition of p21contributes to KDM5B-induced proliferation. - Abstract: Epigenetic alterations such as aberrant expression of histone-modifying enzymes have been implicated in tumorigenesis. Upregulation of lysine (K)-specific demethylase 5B (KDM5B) has been reported in a variety of malignant tumors. However, the impact of KDM5B in glioma remains unclear. The objective of this study was to investigate the expression and prognostic value of KDM5B in glioma. In clinical glioma samples, we found that KDM5B expression was significantly upregulated in cancer lesions compared with normal brain tissues. Kaplan–Meier analysis showed that patients with glioma and higher KDM5B expression tend to have shorter overall survival time. By silencing or overexpressing KDM5B in glioma cells, we found that KDM5B could promote cell growth both in vitro and in vivo. Moreover, we demonstrated that KDM5B promoted glioma proliferation partly via regulation of the expression of p21. Our study provided evidence that KDM5B functions as a novel tumor oncogene in glioma and may be a potential therapeutic target for glioma management.

60 APPLIED LIFE SCIENCES↗

Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer

Lipid metabolism is dysregulated in many human diseases including atherosclerosis, type 2 diabetes and cancers. Fatty acid synthase (FASN), a key lipogenic enzyme involved in de novo lipid biosynthesis, is significantly upregulated in multiple types of human cancers and associates with tumor progression. However, limited data is available to understand underlying biological functions and clinical significance of overexpressed FASN in pancreatic ductal adenocarcinoma (PDAC). Here, upregulated FASN was more frequently observed in PDAC tissues compared with normal pancreas in a tissue microarray. Kaplan–Meier survival analysis revealed that high expression level of FASN resulted in a significantly poor prognosis of PDAC patients. Knockdown or inhibition of endogenous FASN decreased cell proliferation and increased cell apoptosis in HPAC and AsPC-1 cells. Furthermore, we demonstrated that EGFR/ERK signaling accounts for elevated FASN expression in PDAC as ascertained by performing siRNA assays and using specific pharmacological inhibitors. Collectively, our results indicate that FASN exhibits important roles in tumor growth and EGFR/ERK pathway is responsible for upregulated expression of FASN in PDAC. - Highlights: • Increased expression of FASN indicates a poor prognosis in PDAC. • Elevated FASN favors tumor growth in PDAC in vitro. • Activation of EGFR signaling contributes to elevated FASN expression.

60 APPLIED LIFE SCIENCES↗

Upregulation of B23 promotes tumor cell proliferation and predicts poor prognosis in glioma

B23 (also known as Nucleophosmin, NPM, numatrin or NO38) is a ubiquitously expressed phosphoprotein belonging to the nucleoplasmin family of chaperones. In this study we intended to investigate the clinical significance of B23 expression in human glioma and its biological function in glioma cells. Western blot and immunohistochemistry analysis showed that B23 was overexpressed in glioma tissues and glioma cell lines. In addition, the expression level of B23 was positively correlated with glioma pathological grade and Ki-67 expression. Kaplan–Meier analysis revealed that a higher B23 expression in patients with glioma was associated with a poorer prognosis. In vitro, after the release of glioma cell lines from serum starvation, the expression of B23 was upregulated, as well as PCNA (Proliferating Cell Nuclear Antigen) and cyclin A. In addition, knockdown of B23 by small interfering RNA transfection diminished the expression of PCNA, cyclin D1 and arrested cell growth at G1 phase. Taken together, our results implied that B23 could be a candidate prognostic biomarker as well as a potential therapeutical target of glioma. - Highlights: • B23 expression increased as the malignant degree of glioma increased, which was consistent with Ki-67 expression. • High expression of B23 could be a strong determinant of poor prognosis in glioma. • B23 may be involved in the proliferation of glioma in a cell-cycle-dependent pathway. • Knockdown of B23 expression by siRNA could affect the progression of glioma. • B23 may be a potential prognosis biomarker and a possible therapeutic target for glioma.

60 APPLIED LIFE SCIENCES↗

BLZF1 expression is of prognostic significance in hepatocellular carcinoma

BLZF1, a member of b-ZIP family, has been implicated in epigenetic regulation and Wnt/β-catenin signaling. Its expression and clinical significance in human cancers remain largely unknown. In this study, we showed that BLZF1 expression was reduced in hepatocellular carcinoma (HCC) tissues, compared to the paracarcinoma tissues, at both mRNA and protein levels. Results of immunohistochemistry revealed that BLZF1 was presented in both nuclear and cytoplasm. Decreased expression of nuclear and cytosolic BLZF1 in HCC was depicted in 68.2% and 79.2% of the 634 cases. Nuclear BLZF1 expression was significantly associated with tumor multiplicity (P = 0.048) and tumor capsule (P = 0.028), while cytosolic BLZF1 expression was correlated with serum AFP level (P = 0.017), tumor differentiation (P = 0.001) and tumor capsule (P = 0.003). Kaplan–Meier analysis indicated both nuclear and cytosolic BLZF1 expression was associated with poor overall survival. Low nuclear BLZF1 also indicated unfavorable disease-free survival and high tendency of tumor recurrence. Furthermore, multiple Cox regression analysis revealed nuclear BLZF1 as an independent factor for overall survival (Hazard Ratio (HR) = 0.827, 95% confident interval (95%CI): 0.697–0.980, P = 0.029). The prognostic value of BLZF1 was further confirmed by stratified analyses. Collectively, our data suggest BLZF1 is a novel unfavorable biomarker for prognosis of patients with HCC. - Highlights: • BLZF1 expression was much lower in HCC tissues. • Low BLZF1 expression was associated with poor outcomes in a cohort of 634 HCC patients. • Multiple Cox regression analysis indicated nuclear BLZF1 as an independent predictor for overall survival.

60 APPLIED LIFE SCIENCES↗

TROP2 overexpression promotes proliferation and invasion of lung adenocarcinoma cells

Recent studies suggest that the human trophoblast cell-surface antigen TROP2 is highly expressed in a number of tumours and is correlated with poor prognosis. However, its role in non-small cell lung carcinoma (NSCLC) remains largely unknown. Here we examined TROP2 expression by immunohistochemistry in a series of 68 patients with adenocarcinoma (ADC). We found significantly elevated TROP2 expression in ADC tissues compared with normal lung tissues (P < 0.05), and TROP2 overexpression was significantly associated with TNM (tumour, node, metastasis) stage (P = 0.012), lymph node metastasis (P = 0.038), and histologic grade (P = 0.013). Kaplan–Meier survival analysis revealed that high TROP2 expression correlated with poor prognosis (P = 0.046). Multivariate analysis revealed that TROP2 expression was an independent prognostic marker for overall survival of ADC patients. Moreover, TROP2 overexpression enhanced cell proliferation, migration, and invasion in the NSCLC cell line A549, whereas knockdown of TROP2 induced apoptosis and impaired proliferation, migration, and invasion in the PC-9 cells. Altogether, our data suggest that TROP2 plays an important role in promoting ADC and may represent a novel prognostic biomarker and therapeutic target for the disease.

60 APPLIED LIFE SCIENCES↗

MicroRNA-367 is a potential diagnostic biomarker for patients with esophageal squamous cell carcinoma

Purpose: In this study, we investigated whether microRNA-367 (miR-367) may serve as a circulating biomarker and tumor oncogene in esophageal squamous carcinoma (ESCC). Methods: Circulating serum miR-367 was compared by quantitative RT-PCR (qRT-PCR) between 35 ESCC patients and 35 normal control patients, as well paired ESCC tumor tissues and adjacent non-tumor esophageal epithelial tissues in 46 patients. The correlation between serum miR-367 and clinicopathological properties of ESCC patients was assessed. The overall survival (OS) was assessed by Kaplan–Meier method and compared by log-rank test between patients with high serum miR-367 and low serum miR-367. The possibility of miR-367 being independent prognostic factor for ESCC was also assessed. Furthermore, lentivirus-mediated miR-367 downregulation was conducted in ESCC cell lines Kyse30 and TE-1 cells to assess the possible oncogenic effect of miR-367 on ESCC proliferation and cell cycle transition in vitro. Results: MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients, whereas downregulated in ESCC patients after the treatments of esophagectomy and chemotherapy. Serum miR-367 was found to be closely correlated with the clinicopathological properties of differentiation grades, clinical stage and tumor metastasis in ESCC patients. Serum miR-367 was also confirmed to be associated with OS, as well as serving independent prognostic factor in ESCC patients. Moreover, lentivirus-induced miR-367 downregulation inhibited cancer growth and cell cycle transition in Kyse30 and TE-1 cells. Conclusion: MiR-367 is a potential biomarker for ESCC and may act as an oncogene in regulating ESCC development. - Highlights: • MiR-367 was aberrantly upregulated in sera and tumors of ESCC patients. • MiR-367 was downregulated in ESCC patients after esophagectomy or chemotherapy. • Serum miR-367 was correlated with the clinicopathological properties of ESCC patients. • Serum miR-367 was associated with OS in ESCC patients. • lentivirus-induced miR-367 downregulation inhibited ESCC growth and cell cycle transition.

60 APPLIED LIFE SCIENCES↗

miR-625 suppresses cell proliferation and migration by targeting HMGA1 in breast cancer

Dysregulation of microRNA contributes to the high incidence and mortality of breast cancer. Here, we show that miR-625 was frequently down-regulated in breast cancer. Decrease of miR-625 was closely associated with estrogen receptor (P = 0.004), human epidermal growth factor receptor 2 (P = 0.003) and clinical stage (P = 0.001). Kaplan–Meier and multivariate analyses indicated miR-625 as an independent factor for unfavorable prognosis (hazard ratio = 2.654, 95% confident interval: 1.300–5.382, P = 0.007). Re-expression of miR-625 impeded, whereas knockdown of miR-625 enhanced cell viabilities and migration abilities in breast cancer cells. HMGA1 was confirmed as a direct target of miR-625. The expressions of HMGA1 mRNA and protein were induced by miR-625 mimics, but reduced by miR-625 inhibitor. Re-introduction of HMGA1 in cells expressing miR-625 distinctly abrogated miR-625-mediated inhibition of cell growth. Taken together, our data demonstrate that miR-625 suppresses cell proliferation and migration by targeting HMGA1 and suggest miR-625 as a promising prognostic biomarker and a potential therapeutic target for breast cancer. - Highlights: • miR-625 expression was significantly decreased in breast cancer. • Decrease of miR-625 was associated with poor clinical outcomes and unfavorable overall survival. • miR-625 overexpression inhibits cell proliferation and migration in vitro. • miR-625 directly targets and suppresses the expression of HMGA1.

60 APPLIED LIFE SCIENCES↗

The up-regulation of long non-coding RNA CCAT2 indicates a poor prognosis for prostate cancer and promotes metastasis by affecting epithelial-mesenchymal transition

Recently, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in human cancer biology. LncRNA CCAT2 is a novel identified lncRNA that was previously reported to be up-regulated in different cancers, however, its role in prostate cancer remains unclear. The aim of this study was to investigate the expression and role of lncRNA CCAT2 in prostate cancer. The expression levels of lncRNA CCAT2 in PCa tissues and cell lines (DU145 and 22RV1) were evaluated by quantitative real-time PCR (qRT-PCR), and its association with prognosis of patients was analyzed by statistical analysis. Furthermore, the effect of CCAT2 on proliferation, migration, and invasion was studied in PCa cells. We found that the expression level of CCAT2 was higher in PCa tissues and cells compared to adjacent non-tumor tissues and normal prostate stromal immortalized cells WPMY-1. Kaplan-Meier survival analysis revealed that patients with high CCAT2 expression level had poorer overall survival and progression-free survival than those with low CCAT2 expression. Furthermore, multivariate analysis showed that the status of CCAT2 expression was an independent prognostic indicator for this disease. We also found that knockdown of CCAT2 could inhibit cell growth, migration, and invasion in vitro. In addition, knockdown of CCAT2 stimulated epithelial-mesenchymal transition (EMT) through abrogating N-cadherin, vimentin expression and intensifing the expression levels of E-cadherin. In conclusion, our data suggested that lncRNA CCAT2 was a novel molecule involved in PCa progression, which provided a potential prognostic biomarker and therapeutic target for new therapies in patients with prostate cancer. - Highlights: • LncRNA CCAT2 is identified with overexpression in prostate cancer tissues and cell lines. • High expression of lncRNA CCAT2 can be an independent prognostic factor for overall survival and progression-free survival. • Knockdown of lncRNA CCAT2 can inhibit cell growth, migration, and invasion in vitro study. • Knockdown of lncRNA CCAT2 stimulates metastasis of prostate cancer cell through regulating EMT-associated gene expression including N-cadherin, Vimentin and E-cadherin.

60 APPLIED LIFE SCIENCES↗