Expression of GRK2 and IGF1R in hepatocellular carcinoma: clinicopathological and prognostic significance

2017 ◽  
Vol 70 (9) ◽  
pp. 754-759 ◽  
Author(s):  
Song-Bai Lin ◽  
Li Zhou ◽  
Zhi-Yong Liang ◽  
Wei-Xun Zhou ◽  
Ye Jin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Potential Marker ◽  
Tumour Node Metastasis Stage ◽  
Clinicopathological Significance ◽  
Igf1r Expression

AimIt has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinicopathological and prognostic significance of GRK2 and IGF1R in HCC.MethodsExpression of GRK2 and IGF1R was first detected by tissue microarray-based immunohistochemistry in 156 patients with HCC. Staining results, termed the H-score, were then correlated with clinicopathological variables and patient survival. Finally, the prognostic value of GRK2 and IGF1R was validated in the publically available TCGA (The Cancer Genome Atlas) RNA-sequencing database.ResultsThe H-score of GRK2 staining (which was significantly lower in tumour than non-tumour tissue) was negatively associated with that of IGF1R with a reverse trend. No clinicopathological significance of the proteins was found except for a relationship between tumoral IGF1R expression and tumour–node–metastasis stage. In univariate analysis, high IGF1R expression predicted poor overall and disease-free survival, whereas GRK2 was not prognostic. In multivariate analysis, IGF1R was significant for overall survival. Furthermore, IGF1R was also of prognostic value in the TCGA database.ConclusionsOur data indicate that GRK2 and IGF1R show a negative correlation in HCC. IGF1R could be a potential marker of poor prognosis for this malignancy.

Is It The Time That We Can Depend on Bioscore as a New Staging System in Non-Metastatic Breast Cancer to Predict the Disease-Free Survival?

2021 ◽  
Author(s):  
Rehab Farouk Mohamed ◽  
Donia Hussein Abd El Hameed ◽  
Mohamed Alaa Eldeen Hassan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Prognostic Value ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Free Survival ◽  
Disease Free

Abstract Purpose: Novel molecular characterization of breast cancer with cellular markers has allowed a new classification that offers prognostic value. This study investigates the prognostic value of the Bioscore among non-metastatic breast cancer patients with respect to disease free survival (DFS).Methods: This study included 317 patients with non-metastatic surgically treated breast cancer; they were identified in the period from January 2015 to December 2018 at Clinical Oncology Department of Assiut University Hospital. Many variables were used; pathologic stage (PS), T stage (T), nodal stage (N), grade (G), estrogen receptor (ER), progesterone receptors (PR), and human epidermal growth factor receptor (HER2) status. Univariate & two multivariate analyses were performed to identify which of these variables are associated with disease-free survival (DFS). Results: The only significant factors in the Univariate analysis were PS3, T2, T3, T4, N3, G2, G3, ER -ve, PR -ve, and HER2 –ve. The factors which were significant in the first multivariate analysis; PS3, G3, ER –ve, and in the second one were; T2, T4, N3, G3, and ER –ve. Two sets of models were built to determine the utility of combining variables. Models incorporating G and E status had the highest C-index (0.72) for T+N + G + ER in comparison with (0.69) for (PS+ G + ER) and the lowest AIC (953.01) for T + N + G + E and (966.9) for PS + G + E. Conclusions: This study confirms the prognostic significance of bioscore in non-metastatic breast cancer in concerning DFS.

The Indications for Hepatectomy for Multinodular Hepatocellular Carcinoma: Experience from a Single Institution

2015 ◽  
Vol 32 (2) ◽  
pp. 82-89 ◽  
Author(s):  
Yuan-da Zhou ◽  
Hui-kai Li ◽  
Yun-long Cui ◽  
Ti Zhang ◽  
Qiang Li
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Rank Test ◽  
Morbidity Rate ◽  
Single Institution ◽  
Multiple Tumor ◽  
Prognostic Risk Factors

Aims: This study was conducted in order to investigate the indications for hepatecomy for multinodular hepatocellular carcinoma (MNHCC) in single institution. Methods: We retrospectively analyzed the medical records from 55 MNHCC patients, mainly with Child-Pugh A liver function, who underwent hepatectomy from January 2006 to December 2008. Both short- and long-term outcomes were analyzed. In addition, the prognostic significance of clinicopathological factors on overall survival (OS) was investigated by univariate analysis using the log-rank test. A Cox proportional hazards model was used in a subsequent multivariate analysis. Results: The perioperative morbidity rate (grade II or higher) was 18.2% (n = 10), and the in-hospital mortality rate was 3.6%. The median OS was 23.9 months (range, 2.5-84 months), whereas the median disease-free survival was 8.75 months (range, 1-65 months). Independent prognostic risk factors of 5-year OS included the number of tumors >2 (p = 0.032) and gross morphology indicating multiple tumor nodules scattered throughout the liver (p = 0.009). Conclusions: The postoperative morbidity and mortality rates were acceptable. The number of tumors >2 and gross morphology indicating multiple tumor nodules scattered throughout the liver were independent prognostic risk factors for patients with MNHCC after hepatectomy. Patients with both of these features had a very poor prognosis and were not considered suitable for surgery.

Coexpression of PDGFR-Alpha, PDGFR-Beta and VEGF as a Prognostic Factor in Patients with Hepatocellular Carcinoma

2011 ◽  
Vol 26 (2) ◽  
pp. 108-116 ◽  
Author(s):  
Li Chen ◽  
Yan Shi ◽  
Cheng-ying Jiang ◽  
Li-xin Wei ◽  
Ya-li Lv ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Cox Proportional Hazards Model ◽  
Cox Regression Analysis

Aims To evaluate the prognostic value of vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor-alpha (PDGFR-α) and beta (PDGFR-β) expression in patients with hepatocellular carcinoma (HCC). Methods The expression of PDGFR-α, PDGFR-β and VEGF in 63 HCC patients who underwent curative resection was examined by immunohistochemistry (IHC). The correlations between the expression of these biomarkers and the clinicopathological characteristics were analyzed. Patient survival was analyzed by univariate analysis and Cox proportional hazards model. Results Univariate survival analysis showed that PDGFR-α or PDGFR-β overexpression was of no prognostic significance in predicting disease-free survival (DFS) and overall survival (OS) (p>0.05), while VEGF overexpression and PDGFR-α/PDGFR-β/VEGF coexpression were significantly correlated with worse DFS and poorer OS in HCC patients (P<0.05). More importantly, PDGFR-α/PDGFR-β/VEGF coexpression was an independent prognostic marker for poor survival as indicated by multivariate Cox regression analysis (DFS, hazard ratio 3.122, p=0.001; OS, hazard ratio 4.260, p=0.000). Conclusions Coexpression of PDGFR-α, PDGFR-β and VEGF could be considered an independent prognostic biomarker for predicting DFS and OS in HCC patients. This result could be used to identify patients at a higher risk of tumor recurrence and poor prognosis, and help to select therapeutic schemes for the treatment of HCC.

scholarly journals The Predictive Value of Vessels Encapsulating Tumor Clusters in Treatment Optimization for Recurrent Early-Stage Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zhi-Yuan Chen ◽  
Zhi-Xing Guo ◽  
Liang-He Lu ◽  
Jie Mei ◽  
Wen-Ping Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Predictive Value ◽  
Early Stage ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Survival Outcomes ◽  
Treatment Optimization ◽  
Initial Hepatectomy ◽  
Significant Difference

Abstract Background. The vessels encapsulating tumor clusters (VETC) pattern is an effective predictor of survival in patients with hepatocellular carcinoma (HCC) after resection. The predictive value of VETC in recurrent early-stage HCC remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early-stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA). Methods. From December 2005 to December 2016, 138 patients who underwent RHR and 188 patients who underwent RFA were enrolled. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of treatment for patients with or without the VETC pattern was investigated. Results. Among VETC-positive HCC patients, 50 patients underwent RHR, and 69 patients underwent RFA; among VETC-negative HCC patients, 88 patients underwent RHR, and 119 patients underwent RFA. There was no significant difference between the RHR and RFA groups in disease-free survival (DFS) or overall survival (OS) as determined by univariate analysis of the whole cohort. In the subgroup analysis of the VETC-positive cohort, the patients in the RHR group had a longer median DFS time compared to those in the RFA group (15.0 vs 5.0 months, P=0.001). Similarly, the patients in the RHR group had a longer median OS time compared to those in the RFA group (39.5 vs 19 months, P=0.001). In the VETC-negative cohort, there was no significant difference in DFS and OS rates between the RHR and RFA groups (P>0.05).Conclusions. The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early-stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.

scholarly journals Cyclin E correlates with malignancy and adverse prognosis in adrenocortical tumors

2004 ◽  
pp. 809-817 ◽  
Author(s):  
F Tissier ◽  
A Louvel ◽  
S Grabar ◽  
AM Hagnere ◽  
J Bertherat ◽  
...  
Keyword(s):  
Cyclin E ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Uniparental Disomy ◽  
Disease Free Survival ◽  
Wilcoxon Test ◽  
Free Survival ◽  
Adrenocortical Tumors ◽  
Potential Marker ◽  
Disease Free

OBJECTIVE: In many cases, the prognosis of an adrenocortical tumor cannot be determined from pathologic findings alone. We investigated cyclin E levels as a potential marker. METHODS: We studied 57 tumors by immunohistochemical staining with an anticyclin E antibody. We also evaluated clinical and pathologic factors (McFarlane staging and Weiss score) and previously validated genetic markers (17p13 loss of heterozygosity, 11p15 uniparental disomy, and overexpression of the IGF-II gene) for these tumors. Disease-free survival was estimated in 49 patients who underwent curative surgery. RESULTS: Cyclin E overproduction (> or =5%) was associated with the malignant phenotype and was strongly correlated with tumor size (P<0.0001), Weiss score (P<0.0001) and the presence of genetic abnormalities in tumors (P<0.001) (nonparametric Wilcoxon test and Fisher's exact test). Within a median follow-up of 44.1 months, seven patients exhibited a recurrence and two patients died from other causes. Cyclin E overproduction was significantly associated with shorter disease-free survival in univariate analysis (P=0.016; RR: 7.6), as were histologic grade (Weiss score > or =4; P=0.0006; RR: 18), 17p13 LOH (P=0.014, RR: 14.9), 11p15 UPD (P=0.003, RR: 11.8) and overexpression of the IGF-II gene (P=0.015, RR: 13.8). CONCLUSION: This study shows that cyclin E overproduction is of adverse prognostic significance in adrenocortical tumors.

scholarly journals Prognostic significance of microRNA-135 in patients with digestive system cancers: a systematic review and meta-analysis

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Ce Chao ◽  
Chen Sang ◽  
Min Wang ◽  
Zijin Wang ◽  
Yanfei Li ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Large Scale ◽  
Digestive System ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Cochrane Library ◽  
Free Survival ◽  
Non Coding Rna

Abstract Background: MicroRNA-135 (miR-135) is a well-known non-coding RNA that has been demonstrated to participate in tumorigenesis and cancer development; however, the clinical prognostic value of miR-135 in digestive system cancers remains controversial. This meta-analysis aims to explore the potential value of miR-135 as a prognostic marker for digestive system cancers. Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible articles published before 31 August 2019. Stata 12.0 software was used to analyze the overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) rates to access the prognostic value of miR-135 in digestive system cancers. We then used The Cancer Genome Atlas (TCGA) datasets to validate the meta-analysis results. Results A total of 1470 patients from 17 studies were included in this meta-analysis. The pooled results showed that enhanced miR-135 expression was significantly associated with poor OR (hazard ratio (HR): 1.790; 95% confidence interval (95% CI): 1.577–2.031; P=0.000), DFS (HR: 1.482; 95% CI: 0.914–2.403; P=0.110), and RFS (HR: 3.994; 95% CI: 1.363–11.697; P=0.012) in digestive system cancers. A sensitivity analysis confirmed the reliability of our findings, and no significant publication bias was observed. Conclusion: MiR-135 can be used as a novel biomarker for patients with digestive system cancers. We look forward to future large-scale clinical studies that will investigate the prognostic value of miR-135.

scholarly journals The Predictive Value of Vessels Encapsulating Tumor Clusters in Treatment Optimization for Recurrent Early-stage Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Zhi-Yuan Chen ◽  
Zhi-Xing Guo ◽  
Liang-He Lu ◽  
Jie Mei ◽  
Wen-Ping Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Predictive Value ◽  
Early Stage ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Survival Outcomes ◽  
Treatment Optimization ◽  
Initial Hepatectomy ◽  
Significant Difference

Abstract Background: The predictive value of vessels encapsulating tumor clusters (VETC) in recurrent early-stage Hepatocellular Carcinoma (HCC) remains unclear. Therefore, the aim of the present study was to investigate the prognostic significance of VETC in patients with recurrent early-stage HCC after repeat hepatic resection (RHR) or radiofrequency ablation (RFA). Methods: From December 2005 to December 2016, 138 patients receiving RHR and 188 patients receiving RFA were recruited. VETC was evaluated by immunohistochemical staining for CD34. The survival outcomes of patients with VETC pattern or not were investigated. Results: There was no significant difference between the RHR and RFA groups in disease-free survival (DFS) or overall survival (OS) as determined by univariate analysis of the whole cohort. In the subgroup analysis of the VETC-positive cohort, the patients in the RHR group showed a longer median DFS time in contrast to those in the RFA group (15.0 vs 5.0 months, P=0.001). Similarly, the patients in the RHR group showed a longer median OS time in contrast to those in the RFA group (39.5 vs 19 months, P=0.001). In the VETC-negative cohort, no significant differences in DFS and OS rates between the RHR and RFA groups were observed (P>0.05).Conclusions: The results of our study suggested that RHR was relatively safe and superior to RFA in improving survival outcomes for recurrent early-stage HCC after initial hepatectomy. Furthermore, the VETC pattern may represent a reliable marker for selecting HCC patients who may benefit from RHR.

scholarly journals The Prognostic Significance of Combined Pretreatment Fibrinogen and Neutrophil-Lymphocyte Ratio in Various Cancers: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Rongqiang Liu ◽  
Shiyang Zheng ◽  
Qing Yuan ◽  
Peiwen Zhu ◽  
Biao Li ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Regression Analyses ◽  
Free Survival ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Meta Regression

Purpose. The prognostic value of a new scoring system, termed F-NLR, that combines pretreatment fibrinogen level with neutrophil-lymphocyte ratio has been evaluated in various cancers. However, the results are controversial. The purpose of this study was to comprehensively analyze the prognostic value of F-NLR score in patients with cancers. Methods. An integrated search of relevant studies was conducted by screening the PubMed and Embase databases. Pooled hazard ratios, with 95% confidence intervals (CIs), for overall survival (OS) and disease-free survival (DFS)/progression-free survival (PFS) were calculated to estimate the prognostic significance of F-NLR score in patients with various tumors. A random effects model was used for comprehensive analysis, and subgroup and meta-regression analyses were used to explore sources of heterogeneity. Results. Thirteen articles reporting data from of 4747 patients were included in the study. Pooled analysis revealed that high F-NLR score was significantly associated with poor OS ( HR = 1.77 ; 95% CI, 1.51–2.08) and poor DFS/PFS ( HR = 1.63 ; 95% CI, 1.30–2.05). Subgroup and meta-regression analyses did not alter the prognostic role of F-NLR score in OS and DFS/PFS. Conclusions. Increased F-NLR score is significantly associated with poor prognosis in patients with cancers and can serve as an effective prognostic indicator.

scholarly journals Transcript levels of spindle and kinetochore-associated complex 1/3 as prognostic biomarkers correlated with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
De-Chen Yu ◽  
Xiang-Yi Chen ◽  
Xin Li ◽  
Hai-Yu Zhou ◽  
De-Quan Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Complex ◽  
Immune Cell ◽  
Prognostic Significance ◽  
Tumor Development ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Tumor Stage ◽  
Prognostic Biomarkers ◽  
High Expression

AbstractThe spindle and kinetochore-associated protein complex (Ska) is an essential component in chromosome segregation. It comprises three proteins (Ska1, Ska2, and Ska3) with theorized roles in chromosomal instability and tumor development, and its overexpression has been widely reported in a variety of tumors. However, the prognostic significance and immune infiltration of Ska proteins in hepatocellular carcinoma (HCC) are not completely understood. The bioinformatics tools Oncomine, UALCAN, gene expression profiling interactive analysis 2 (GEPIA2), cBioPortal, GeneMANIA, Metascape, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of the Ska protein complex in HCC patients. We found that the mRNA expression of the Ska complex was markedly upregulated in HCC. High expression of the Ska complex is closely correlated with tumor stage, patient race, tumor grade, and TP53 mutation status. In addition, high expression of the Ska complex was significantly correlated with poor disease-free survival, while the high expression levels of Ska1 and Ska3 were associated with shorter overall survival. The biological functions of the Ska complex in HCC primarily involve the amplification of signals from kinetochores, the mitotic spindle, and (via a MAD2 invasive signal) unattached kinetochores. Furthermore, the expression of the complex was positively correlated with tumor-infiltrating cells. These results may provide new insights into the development of immunotherapeutic targets and prognostic biomarkers for HCC.

scholarly journals Identification of glycolysis related pathways in pancreatic adenocarcinoma and liver hepatocellular carcinoma based on TCGA and GEO datasets

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ji Li ◽  
Chen Zhu ◽  
Peipei Yue ◽  
Tianyu Zheng ◽  
Yan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Energy Metabolism ◽  
Pancreatic Adenocarcinoma ◽  
Digestive System ◽  
Prognostic Significance ◽  
R Package ◽  
The Cancer Genome Atlas ◽  
System Structure ◽  
Liver Hepatocellular Carcinoma

Abstract Background Abnormal energy metabolism is one of the characteristics of tumor cells, and it is also a research hotspot in recent years. Due to the complexity of digestive system structure, the frequency of tumor is relatively high. We aim to clarify the prognostic significance of energy metabolism in digestive system tumors and the underlying mechanisms. Methods Gene set variance analysis (GSVA) R package was used to establish the metabolic score, and the score was used to represent the metabolic level. The relationship between the metabolism and prognosis of digestive system tumors was explored using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Volcano plots and gene ontology (GO) analyze were used to show different genes and different functions enriched between different glycolysis levels, and GSEA was used to analyze the pathway enrichment. Nomogram was constructed by R package based on gene characteristics and clinical parameters. qPCR and Western Blot were applied to analyze gene expression. All statistical analyses were conducted using SPSS, GraphPad Prism 7, and R software. All validated experiments were performed three times independently. Results High glycolysis metabolism score was significantly associated with poor prognosis in pancreatic adenocarcinoma (PAAD) and liver hepatocellular carcinoma (LIHC). The STAT3 (signal transducer and activator of transcription 3) and YAP1 (Yes1-associated transcriptional regulator) pathways were the most critical signaling pathways in glycolysis modulation in PAAD and LIHC, respectively. Interestingly, elevated glycolysis levels could also enhance STAT3 and YAP1 activity in PAAD and LIHC cells, respectively, forming a positive feedback loop. Conclusions Our results may provide new insights into the indispensable role of glycolysis metabolism in digestive system tumors and guide the direction of future metabolism–signaling target combined therapy.

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