scholarly journals Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: a systematic review with meta-analysis

2021 ◽  
Vol 13 ◽  
pp. 175883592098707
Author(s):  
Carolina Méndez-Blanco ◽  
Paula Fernández-Palanca ◽  
Flavia Fondevila ◽  
Javier González-Gallego ◽  
José L. Mauriz
Keyword(s):  
Hepatocellular Carcinoma ◽  
Subgroup Analysis ◽  
Tumor Size ◽  
Vasculogenic Mimicry ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Hypoxia Inducible Factors ◽  
Free Survival ◽  
Node Metastasis ◽  
Clinicopathological Significance

Background: Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients. Methods: We systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the I2 statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger’s test. Results: HIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor–node–metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration. Conclusions: HIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers.

scholarly journals Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: a propensity score matching analysis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chih-Wen Lin ◽  
Tsung-Chin Wu ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Pei-Min Hsieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Free Survival ◽  
Before And After ◽  
Disease Free

Abstract Background Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups. Methods We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis. Results In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM. Conclusion The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

scholarly journals Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: A propensity score matching analysis

2020 ◽  
Author(s):  
Chih-Wen Lin ◽  
Tsung-Chin Wu ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Pei-Min Hsieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Free Survival ◽  
Before And After ◽  
Disease Free

Abstract Background: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups.Methods: We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis.Results: In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM.Conclusion: The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

scholarly journals Prognostic and clinicopathological significance of PD-1 expression in hepatocellular carcinoma: a meta-analysis

2020 ◽  
Vol 48 (10) ◽  
pp. 030006052096267
Author(s):  
Qian Zhang ◽  
Kexiang Zhou ◽  
Wei Liang ◽  
Wei Xiong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Alpha Fetoprotein ◽  
Biomedical Literature ◽  
Free Survival ◽  
Programmed Cell Death 1 ◽  
Clinicopathological Significance ◽  
Disease Free

Objective We performed a meta-analysis to evaluate the prognostic and clinicopathological significance of programmed cell death-1 (PD-1) expression in patients with hepatocellular carcinoma (HCC). Methods We searched the Wanfang, Chinese Biomedical Literature, CNKI, PubMed, Embase, and Web of Science databases for relevant articles from inception to 1 July 2020. Statistical analysis was performed using RevMan 5.3 (Cochrane, London, UK) and Stata 14.0 software (StataCorp LP, College Station, TX, USA). Results Eight studies involving 732 patients with HCC were included. Higher expression of PD-1 predicted longer disease-free survival [hazard ratio (HR) 0.53, 95% confidence interval (CI): 0.38–0.72]. No significant correlation was observed between PD-1 expression and overall survival (HR 0.89, 95% CI: 0.58–1.35). PD-1 expression was correlated with age [odds ratio (OR) 0.66, 95% CI: 0.46–0.94] and alpha-fetoprotein level (OR 2.27, 95% CI: 1.45–3.55); no correlation was observed with sex, tumor size, tumor metastasis, hepatitis B virus history, tumor stage, or tumor multiplicity. Sensitivity analysis demonstrated no excessive effect on stability of the pooled results. No significant publication bias was found among the identified studies. Conclusion PD-1 overexpression predicted better disease-free survival in patients with HCC. Moreover, PD-1 expression was associated with age and alpha-fetoprotein level.

scholarly journals Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: A propensity score matching analysis

2021 ◽  
Author(s):  
Chih-Wen Lin ◽  
Tsung-Chin Wu ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Pei-Min Hsieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Free Survival ◽  
Before And After ◽  
Disease Free

Abstract Background: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups.Methods: We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis.Results: In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM.Conclusion: The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

scholarly journals The Prognostic Value of lncRNA SNHG3 in Cancer Patients: A meta-analysis

2020 ◽  
Author(s):  
Jie Wang ◽  
Pingyong Zhong ◽  
Hao Hua
Keyword(s):  
Cancer Patients ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Cochrane Library ◽  
Multiple Cancer ◽  
Free Survival ◽  
Node Metastasis ◽  
Hazard Ratios ◽  
Clinicopathological Significance

Abstract Background:Small nucleolar RNA host gene 3 (SNHG3) is a promising long non-coding RNA that may possess prognostic value for different types of tumors. The objective of this meta-analysis is to evaluate the prognostic value of lncRNA SNHG3 in cancer patients.Methods:A systematic literature search of the PubMed, Cochrane Library, EMBASE, Medline, Web of Science, CNKI, Weipu, and Wanfang electronic databases was carried out in this meta-anaysis. The synthetic hazard ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were obtained to determine the prognostic and clinicopathological significance of SNHG3 expression in tumors. Results:The final meta-anaysis included 17 studies that contained 2072 patients. The pooled results provided evidence that SNHG3 overexpression predicted reduced overall survival (OS) (HR=2.15, 95%CI: 1.76–2.63, P<0.00001), recurrence-free survival (RFS) ( HR=2.22, 95%CI: 1.04–4.76, P=0.04) and disease-free survival (DFS) (HR=2.04, 95%CI: 1.35–3.09, P=0.0007) for various cancers. Additionally, the SNHG3 overexpression was concerned with tumor node metastasis (TNM) stage (III/IV vs. I/II, OR=2.91, 95%CI: 1.60–5.29, P=0.0005), lymph node metastasis (LNM) (positive vs negative, OR=5.00,95%CI:2.82–8.87,P＜0.00001), distant metastasis (DM) (positive vs negative, OR=2.29, 95%CI: 1.52–3.47, P<0.0001) and tumor size (larger vs smaller, OR=1.80, 95%CI: 1.04–3.11, P=0.04).Conclusions:Our results indicated that SNHG3 overexpression was closely correlated with shorter OS in multiple cancer types, suggesting that SNHG3 might function as a promising predictor for clinical outcomes in cancer.

scholarly journals Prognostic Impact of Monocyte to Lymphocyte Ratio in Clinical Outcome for Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 9 ◽  
pp. 1948
Author(s):  
Masoud Nouri-Vaskeh ◽  
Mohammad Mirza-Aghazadeh-Attari ◽  
Fariba Pashazadeh ◽  
Saber Azami-Aghdash ◽  
Hadi Alizadeh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Subgroup Analysis ◽  
Meta Analysis ◽  
Prognostic Significance ◽  
Surrogate Marker ◽  
Disease Free Survival ◽  
Systemic Review ◽  
Significant Heterogeneity ◽  
Prognostic Impact ◽  
Free Survival

Background: Lymphocyte to monocyte ratio (LMR) is a surrogate marker of systemic inflammation which is shown to be related to patient’s survival in multiple malignancies. An important implication of this marker potentially is neoplasms in which there is no correlation between prognosis and histopathological staging, or has no reliable chemical markers associated with prognosis. Herein, this meta-analysis aimed to investigate the prognostic role of LMR in the patients with hepatocellular carcinoma (HCC).Methods: In the current systemic review and meta-analysis, we conducted a systemic search of databases and indexing sources, including Medline (PubMed), EMBASE, Cochrane, Scopus, and ProQuest up to May 2019. We include studies evaluating the prognostic significance of LMR on patients with HCC. Overall survival (OS), disease free survival (DFS) and recurrence free survival (RFS) values were extracted from the studies and analyzed. The pooled hazard ratio with 95% confidence interval explored to identify the prognostic value of LMR in survival of the patients with HCC.Results: A total of 12 studies with a total sample size of 3750 were included. There was significant heterogeneity among the studies, so subgroup analysis was also performed. Overall analysis regarding OS showed an insignificant relationship between LMR and patient’s prognosis, subgroup based on LMR cut-offs did not yield any significant result, subgroup analysis for RFS founded statistically significant results and LMR was significantly related to DFS.Conclusion: High LMR was associated with increased DFS and RFS, in return this correlation was not observed for OS.

scholarly journals Clinical features and outcomes of combined hepatocellular carcinoma and cholangiocarcinoma versus hepatocellular carcinoma versus cholangiocarcinoma after surgical resection: A propensity score matching analysis

2020 ◽  
Author(s):  
Chih-Wen Lin ◽  
Hung-Yu Lin ◽  
Chao-Ming Hung ◽  
Pei-Min Hsieh ◽  
Tsung-Chin Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Clinicopathological Features ◽  
Free Survival ◽  
Before And After ◽  
Disease Free

Abstract Background: Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups.Methods: We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis.Results: In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM.Conclusion: The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

scholarly journals In Silico Identification of Contradictory Role of ADAMTS5 in Hepatocellular Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382098682
Author(s):  
Zhipeng Zhu ◽  
Jiuhua Xu ◽  
Xiaofang Wu ◽  
Sihao Lin ◽  
Lulu Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Subgroup Analysis ◽  
Prognostic Value ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
The Impact

Background: ADAMTS5 has different roles in multiple types of cancers and participates in various molecular mechanisms. However, the prognostic value of ADAMTS5 in patients with hepatocellular carcinoma (HCC) still remains unclear. We carried the study to evaluate the prognostic value and identified underlying molecular mechanisms in HCC. Methods: Firstly, the association of ADAMTS5 expression and clinicopathological parameters was evaluated by in GSE14520. Next, ADAMTS5 expression in HCC was performed using GSE14520, GSE36376, GSE76427 and The Cancer Genome Atlas (TCGA) profile. Furthermore, Kaplan-Meier analysis, Univariate and Multivariate Cox regression analysis, subgroup analysis was performed to evaluate the prognostic value of ADAMTS5 in HCC. Finally, GO enrichment analysis, gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were performed to revealed underlying molecular mechanisms. Result: The expression of ADAMTS5 was positively correlated with the development of HCC. Next, high ADAMTS5 expression was significantly associated with poorer survival (all P < 0.05) and the impact of ADAMTS5 on all overall survival (OS), disease-free survival (DFS), relapse-free survival (RFS), disease specific survival (DSS) and progression free interval (PFI) was specific for HCC among other 29 cancer types. Subgroup analysis showed that ADAMTS5 overexpression was significantly associated with poorer OS in patients with HCC. Finally, ADAMTS5 might participate in the status conversion from metabolic-dominant to extracellular matrix-dominant, and the activation of ECM-related biological process might contribute to high higher mortality risk for patients with HCC. Conclusion: ADAMTS5 may play an important role in the progression of HCC, and may be considered as a novel and effective biomarker for predicting prognosis for patients with HCC.

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