scholarly journals Clinicopathological Significance of MicroRNA-20b Expression in Hepatocellular Carcinoma and Regulation of HIF-1αand VEGF Effect on Cell Biological Behaviour

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Tong-min Xue ◽  
Li-de Tao ◽  
Miao Zhang ◽  
Jie Zhang ◽  
Xia Liu ◽  
...  

miRNA-20b has been shown to be aberrantly expressed in several tumor types. However, the clinical significance of miRNA-20b in the prognosis of patients with hepatocellular carcinoma (HCC) is poorly understood, and the exact role of miRNA-20b in HCC remains unclear. The aim of the present study was to investigate the association of the expression of miR-20b with clinicopathological characteristics and overall survival of HCC patients analyzed by Kaplan-Meier analysis and Cox proportional hazards regression models. Meanwhile, the HIF-1αand VEGF targets of miR-20b have been confirmed. We found not only miR-20b regulation of HIF-1αand VEGF in normal but also regulation of miR-20b in hypoxia. This mechanism would help the tumor cells adapt to the different environments thus promoting the tumor invasion and development. The whole study suggests that miR-20b, HIF-1α, and VEGF serve as a potential therapeutic agent for hepatocellular carcinoma.

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Rosero ◽  
P Jones ◽  
I Goldenberg ◽  
W Zareba ◽  
K Stein ◽  
...  

Abstract Background The role of cardiovascular implantable electronic device (CIED)-derived activity to predict inappropriate implantable cardioverter-defibrillator (ICD) therapy is not known. The Multicenter Automatic Defibrillator Implantation Trial – Reduce Inappropriate Therapy (MADIT-RIT) enrolled 1500 patients with contemporary indication for an ICD or a CRT-D. We aimed to identify whether activity, as a digital biomarker, predicted inappropriate therapy. Methods In 1500 patients enrolled in MADIT-RIT, CIED-derived patient activity was acquired daily. CIED-derived activity was averaged for the first 30 days following randomization and utilized in this study to predict inappropriate therapy post- 30-day. Kaplan-Meier survival analysis and multivariate Cox proportional hazards regression models were used to evaluate first inappropriate therapy by 30-day CIED-derived patient activity quintiles, and by 30-day device derived patient activity as a continuous measurement. Results There were a total of 1463 patients with activity data available (90%), 135 patients received at least one inappropriate therapy during the post-30 day follow-up period. Patients in the highest quintile (Q5) of CIED-derived activity (more active) were younger, more often males and more likely to have had a prior ablation of an atrial arrhythmia. Patients in the highest quintile of 30-day CIED-derived median activity had the highest risk of receiving inappropriate therapy, 21% at 2 years as compared 7–11% in the other four quintiles (Figure, p<0.001 for the overall duration). Patients with the highest level of 30-day median patient activity (Q5) had 1.75 times higher risk of any inappropriate therapy as compared with lower levels of activity, Q1-Q4 (HR=1.75, 95% CI: 1.23–2.50, p<0.002). Each 10% increase in CIED-derived 30-day median patient activity was associated with a significant, 73% increase in risk of receiving inappropriate therapy (HR=1.73, 95% CI: 1.17–2.54, p=0.005). Patients in the highest quintile for activity had a 68% increase in the risk of SVT excluding atrial fibrillation, atrial flutter or atrial tachycardia (HR=1.69, 95% CI: 1.26–2.25, p=0.004), despite 96% receiving beta-blocker medications. Inappropriate ICD Therapies by Activity Conclusions CIED-derived 30-day median patient activity predicted subsequent inappropriate therapy in ICD and CRT-D patients enrolled in MADIT-RIT. Patients with high levels of 30-day CIED-derived median patient activity were at a significantly higher risk of receiving inappropriate therapy. Activity, as a digital biomarker, may have utility in predicting and managing the risk of inappropriate therapy in this population. Acknowledgement/Funding Boston Scientific


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 879 ◽  
Author(s):  
Mark Antkowiak ◽  
Ahmed Gabr ◽  
Arighno Das ◽  
Rehan Ali ◽  
Laura Kulik ◽  
...  

Introduction: We compared the efficacy of the ALBI (albumin–bilirubin) score to the established Child–Pugh (CP) grade in hepatocellular carcinoma (HCC) patients treated with yttrium-90 radioembolization (Y90). We further assessed the individual contributions of albumin and bilirubin to survival prediction. Methods: 1000 consecutive HCC patients treated with Y90 were included. Overall survival (OS) was assessed using Kaplan Meier analysis. Sub-stratification analyses were performed using CP and ALBI and in subgroups determined by United Network for Organ Sharing (UNOS) or Barcelona Clinic Liver Cancer (BCLC) staging. The independent impact (hazard ratio (HR)) of ALBI, CP, albumin, and bilirubin on survival was assessed using Cox proportional hazards analysis. Results: Median OS for ALBI 1, 2, and 3 grades was 46.7, 19.1, and 8.8 months, respectively. The HR for death for ALBI 2 vs. ALBI 1 was 3.39 (1.75–6.57); ALBI 3 vs. ALBI 1 was 7.58 (3.89–14.79); and the c-index was 0.623. Median OS for CP A, B, and C was 21.7, 11.3, and 6.0 months, respectively. The HR for death for CP B vs. CP A was 2.04 (1.71–2.43); CP C vs. CP A was 3.27 (2.08–5.14); and the c-index was 0.616. Stratified OS showed unique prognostic groups identified by ALBI within CP-B and CP-C. Median OS for albumin grades 1, 2, and 3 was 46.0, 17.1, and 9.1 months, respectively. Median OS for bilirubin grades 1, 2, and 3 was 15.6, 21.0, and 5.8 months, respectively. The HR for death for albumin 2 vs. 1 was 2.48 (1.81–3.41); albumin 3 vs. 1 was 4.74 (3.44–6.54); and the c-index was 0.640. The HR for death for bilirubin 2 vs. 1 was 1.09 (0.82–1.44); bilirubin 3 vs. 1 was 2.37 (1.66–3.40); and the c-index was 0.533. Conclusions: ALBI outperforms CP in survival prognosis in Y90 treated patients. On sub-analyses, serum albumin (not bilirubin) appears to be the main driver of survival prediction. Our study supports the prognostic ability of ALBI and may suggest a role of albumin alone as a biomarker for patients with HCC.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
I.D Poveda Pinedo ◽  
I Marco Clement ◽  
O Gonzalez ◽  
I Ponz ◽  
A.M Iniesta ◽  
...  

Abstract Background Previous parameters such as peak VO2, VE/VCO2 slope and OUES have been described to be prognostic in heart failure (HF). The aim of this study was to identify further prognostic factors of cardiopulmonary exercise testing (CPET) in HF patients. Methods A retrospective analysis of HF patients who underwent CPET from January to November 2019 in a single centre was performed. PETCO2 gradient was defined by the difference between final PETCO2 and baseline PETCO2. HF events were defined as decompensated HF requiring hospital admission or IV diuretics, or decompensated HF resulting in death. Results A total of 64 HF patients were assessed by CPET, HF events occurred in 8 (12.5%) patients. Baseline characteristics are shown in table 1. Patients having HF events had a negative PETCO2 gradient while patients not having events showed a positive PETCO2 gradient (−1.5 [IQR −4.8, 2.3] vs 3 [IQR 1, 5] mmHg; p=0.004). A multivariate Cox proportional-hazards regression analysis revealed that PETCO2 gradient was an independent predictor of HF events (HR 0.74, 95% CI [0.61–0.89]; p=0.002). Kaplan-Meier curves showed a significantly higher incidence of HF events in patients having negative gradients, p=0.002 (figure 1). Conclusion PETCO2 gradient was demonstrated to be a prognostic parameter of CPET in HF patients in our study. Patients having negative gradients had worse outcomes by having more HF events. Time to first event, decompensated heart Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 8 ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
LingLing Zhuang ◽  
Liying Sun ◽  
Jianbing Wu

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the “limma” package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.


2020 ◽  
Author(s):  
Heng Zou ◽  
Wenhao Chen ◽  
Huan Wang ◽  
Li Xiong ◽  
Yu Wen ◽  
...  

Abstract Overview and objective: Although evidence for the application of albumin–bilirubin (ALBI) grading system to assess liver function in hepatocellular carcinoma (HCC) is available, less is known whether it can be applied to determine the prognosis of single HCC with different tumor sizes. This study aimed to address this gap.Methods: Here, we enrolled patients who underwent hepatectomy due to single HCC from the year 2010 to 2014. Analyses were performed to test the potential of ALBI grading system to monitor the long-term survival of single HCC subjects with varying tumor sizes.Results: Overall, 265 participants were recruited. The overall survival (OS) among patients whose tumors were ≤ 7 cm was remarkably higher compared to those whose tumors were > 7 cm. The Cox proportional hazards regression model identified the tumor differentiation grade, ALBI grade, and maximum tumor size as key determinants of the OS. The ALBI grade could stratify the patients who had a single tumor ≤ 7 cm into two distinct groups with different prognoses. The OS between ALBI grades 1 and 2 was comparable for patients who had a single tumor > 7 cm.Conclusions: We show that ALBI grading system can predict disease outcomes of single HCC patients with tumor size ≤ 7 cm. However, the ALBI grade may not predict capability the prognosis of patients with single tumor > 7 cm.


Cardiology ◽  
2018 ◽  
Vol 139 (4) ◽  
pp. 212-218 ◽  
Author(s):  
Yun Shen ◽  
Xueli Zhang ◽  
Yiting Xu ◽  
Qin Xiong ◽  
Zhigang Lu ◽  
...  

Objectives: To investigate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the future development of major adverse cardiovascular events (MACEs). Methods: This study included 253 patients who received subsequent follow-up, and complete data were collected for 234 patients. Independent predictors of MACEs were identified by using the Cox proportional-hazards regression analysis. The prognostic value of FGF21 levels for MACEs was evaluated by Kaplan-Meier survival analysis. Results: Of 229 patients finally enrolled in the analysis, 27/60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132/169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF21 levels were significantly higher in patients with MACEs (p < 0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed patients with a higher serum FGF21 had a significantly lower event-free survival (p = 0.001) than those with a lower level. Further Cox proportional-hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF21 was an independent predictor of MACE occurrence. Conclusions: In patients with CAD at baseline, an elevated serum FGF21 level was associated with the development of a MACE in the future.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3068-3068
Author(s):  
Lingbin Meng ◽  
Rui Ji ◽  
Damian A. Laber ◽  
Xuebo Yan ◽  
Xiaochun Xu

3068 Background: Raf1 kinase inhibitor protein (RKIP) is able to bind Raf1 to inhibit Ras-Raf-MEK-ERK signaling, a major oncogenic pathway. It has been reported that reduced RKIP expression associates with poor prognosis in many cancers, including gastric adenocarcinoma, gliomas and bladder cancer. However, there are only several studies on its role in non-small cell lung cancer (NSCLC) and the conclusion is still controversial. Hence, we performed this study to assess the prognostic significance of RKIP in our NSCLC population. Methods: Between June 2017 and June 2020, 156 NSCLC patients treated at our hospital were included for the present study. None of the patients had received chemotherapy, radiotherapy or surgery before. Their tumor tissues and surrounding normal lung tissues were collected for immunostain and western blot analysis of RKIP expression and ERK signaling. We collected information about gender, age, histological differentiation, tumor size, TNM stage, and lymph node status. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic value of various variables in a univariate and multivariate setting. Results: Immunostain and western blot results showed a lower RKIP expression and a higher p-ERK level in cancer tissues compared with the surrounding normal tissues. A reduced RKIP expression with high level of p-ERK was also observed in TNM stages III and IV as compared with I and II. Pearson's chi-squared test confirmed low RKIP expression associated with poorer TNM stage ( p< 0.001) and N-stage ( p< 0.05). No significant correlation was observed between RKIP expression level and gender, age, histological type or tumor size. Kaplan-Meier survival analysis revealed that patients with low RKIP expression had significantly worse overall survival than patients with high RKIP expression ( p= 0.019, log-rank). This conclusion was consistent in the stage I&II patients ( p= 0.011, log-rank) but not in the stage III&IV patients ( p= 0.711, log-rank). Univariate Cox proportional hazards regression analysis indicated Tumor size, TNM stage and RKIP expression significantly affected overall survival of the NSCLC patients. Multivariate Cox proportional hazards regression analysis confirmed RKIP expression remained a significant predictor of survival after correcting for the effects of Tumor size and TNM stage (hazard ratio = 1.730, 95% confidence interval = 1.017 – 2.942, p = 0.043). Conclusions: In this study, low RKIP expression was a poor prognostic indicator in NSCLC as it significantly correlated with poorer TNM stage, N-status, and overall survival. Our findings suggest that by inhibiting Ras-Raf-MEK-ERK pathway RKIP may play an anti-tumor role in NSCLC.


2019 ◽  
Author(s):  
Shu Yang ◽  
Huan Zhou ◽  
Jun Dong ◽  
Liyi Guo ◽  
Xicheng Wang ◽  
...  

Abstract Background B7-h6, a member of the B7 family molecules, participates in the clearance of tumor cells by binding to NKp30 on NK cells. The expression of B7-H6 in esophageal squamous cell carcinoma and the clinical significance is unknown. The goal of this study was to determine the expression of B7-H6 in esophageal squamous cell carcinoma and the clinical significance of B7-H6 expression. Patients and methods We retrospectively collected clinical data from 145 patients diagnosed with esophageal squamous cell carcinoma between January 2007 and December 2008. These patients had all previously undergone surgical treatment for esophageal cancer, were clearly diagnosed, and had not received chemotherapy or radiotherapy. In addition, pathological tissue samples from the 145 patients were collected to detect the expression of B7-H6 by immunohistochemistry. The chi-square (χ2) test was used to analyse the relationships between B7-H6 and clinicopathological characteristics. The prognosis of the patients were analysed by Cox proportional hazards regression analysis and Kaplan-Meier analysis. Results B7-H6 was present in 133/145 (91.72%) of the esophageal squamous cell carcinoma samples and all localized in the cytoplasm. The expression level of B7-H6 was correlated with T stage (P=0.036) and lymphatic metastasis status (P=0.044). According to the results of the ROC curve analysis, H-score =90 was selected as the cut-off value. The 145 patients were divided into two groups, the high B7-H6 expression (H-score>90) group and the low B7-H6 expression (H-score≤90) group. Cox proportional hazards regression analysis indicated that tumour size (P=0.021), B7-H6 expression (P=0.025) and lymphatic metastasis status (P=0.049) were independent prognostic factors for esophageal squamous cell carcinoma. Kaplan-Meier analysis with the log-rank test demonstrated that the patients with high B7-H6 expression (P = 0.003), lymphatic metastasis (P <0.001) or a tumour size ≥ 3.0 cm (P = 0.001) had significantly worse survival than those with low B7-H6 expression, no lymphatic metastasis or a tumour size < 3.0 cm respectively. Conclusion B7-H6 is widely expressed in esophageal squamous cell carcinoma and high expression of B7-H6 can be used as a predictor of poor prognosis.


2020 ◽  
Vol 163 (2) ◽  
pp. 372-374 ◽  
Author(s):  
Adam W. Kaplon ◽  
Thomas J. Galloway ◽  
Mihir K. Bhayani ◽  
Jeffrey C. Liu

Human papillomavirus (HPV)–positive oropharynx squamous cell carcinoma (OPSCC) is known to have improved survival over HPV-negative disease. However, it is largely unknown whether HPV status similarly affects survival in patients presenting with distant metastatic disease. We queried the National Cancer Database for OPSCC with distant metastasis. Kaplan-Meier curves and Cox proportional hazards regression models controlling for relevant demographics were used to evaluate overall survival. In total, 768 OPSCC cases were available for analysis with HPV and survival data: 50% of cases were HPV negative and 50% were HPV positive. The 1- and 2-year survival for HPV-negative disease was 49% and 27%, respectively, as compared with 67% and 42% in the HPV-positive cohort. HPV positivity was associated with improved median survival in treated and untreated patients. Age, comorbidities, and HPV status were predictive of improved survival on multivariate analysis. HPV-positive OPSCC has improved survival in the setting of distant metastatic presentation as compared with HPV-negative disease and shows greater responsiveness to treatment.


BMJ Open ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. e015101 ◽  
Author(s):  
Hsien-Feng Lin ◽  
Kuan-Fu Liao ◽  
Ching-Mei Chang ◽  
Cheng-Li Lin ◽  
Shih-Wei Lai

ObjectiveThis study aimed to investigate the association between splenectomy and empyema in Taiwan.MethodsA population-based cohort study was conducted using the hospitalisation dataset of the Taiwan National Health Insurance Program. A total of 13 193 subjects aged 20–84 years who were newly diagnosed with splenectomy from 2000 to 2010 were enrolled in the splenectomy group and 52 464 randomly selected subjects without splenectomy were enrolled in the non-splenectomy group. Both groups were matched by sex, age, comorbidities and the index year of undergoing splenectomy. The incidence of empyema at the end of 2011 was calculated. A multivariable Cox proportional hazards regression model was used to estimate the HR with 95% CI of empyema associated with splenectomy and other comorbidities.ResultsThe overall incidence rate of empyema was 2.56-fold higher in the splenectomy group than in the non-splenectomy group (8.85 vs 3.46 per 1000 person-years). The Kaplan-Meier analysis revealed a higher cumulative incidence of empyema in the splenectomy group than in the non-splenectomy group (6.99% vs 3.37% at the end of follow-up). After adjusting for confounding variables, the adjusted HR of empyema was 2.89 for the splenectomy group compared with that for the non-splenectomy group. Further analysis revealed that HR of empyema was 4.52 for subjects with splenectomy alone.ConclusionThe incidence rate ratio between the splenectomy and non-splenectomy groups reduced from 2.87 in the first 5 years of follow-up to 1.73 in the period following the 5 years. Future studies are required to confirm whether a longer follow-up period would further reduce this average ratio. For the splenectomy group, the overall HR of developing empyema was 2.89 after adjusting for age, sex and comorbidities, which was identified from previous literature. The risk of empyema following splenectomy remains high despite the absence of these comorbidities.


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