Hypomethylation of long interspersed nuclear element‐1 promoter is associated with poor outcomes for curative resected hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignancies. Recent studies reveal that tumor microenvironment (TME) components significantly affect HCC growth and progression, particularly the infiltrating stromal and immune cells. Thus, mining of TME-related biomarkers is crucial to improve the survival of patients with HCC. Public access of The Cancer Genome Atlas (TCGA) database allows convenient performance of gene expression-based analysis of big data, which contributes to the exploration of potential association between genes and prognosis of a variety of malignancies, including HCC. The “Estimation of STromal and Immune cells in MAlignant Tumors using Expression data” algorithm renders the quantification of the stromal and immune components in TME possible by calculating the stromal and immune scores. Differentially expressed genes (DEGs) were screened by dividing the HCC cohort of TCGA database into high- and low-score groups according to stromal and immune scores. Further analyses of functional enrichment and protein-protein interaction networks show that the DEGs are mainly involved in immune response, cell adhesion, and extracellular matrix. Finally, seven DEGs have significant association with HCC poor outcomes. These genes contain FABP3, GALNT5, GPR84, ITGB6, MYEOV, PLEKHS1, and STRA6 and may be candidate biomarkers for HCC prognosis.

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Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio as Prognostic Predictors for Hepatocellular Carcinoma Patients with Various Treatments: a Meta-Analysis and Systematic Review

Cellular Physiology and Biochemistry ◽

10.1159/000485396 ◽

2017 ◽

Vol 44 (3) ◽

pp. 967-981 ◽

Cited By ~ 59

Author(s):

Jun Zheng ◽

Jianye Cai ◽

Hui Li ◽

Kaining Zeng ◽

Liying He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Meta Analysis ◽

Palliative Therapy ◽

Neutrophil To Lymphocyte Ratio ◽

Cochrane Library ◽

Platelet To Lymphocyte Ratio ◽

Lymphocyte Ratio ◽

Poor Outcomes ◽

The Cochrane Library

Background/Aims: Systemic inflammatory response (SIR) is widely considered as a preoperative risk factor for hepatocellular carcinoma (HCC) outcomes. The neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), two of the prognostic indices, have been investigated in post-therapeutic recurrence and survival of HCC. Here, we quantify the prognostic value of these two biomarkers and evaluate their consistency in different HCC therapies. Methods: A systematic review of electronic database of the Web of Science, Embase, PubMed and the Cochrane Library was conducted to search for associations between the NLR and PLR in the blood and clinical outcomes of HCC. Overall survival (OS) and recurrence-free survival (RFS) were the primary outcomes, and hazard ratios (HRs) and 95% confidence intervals (95% CIs) were explored as effect measures. Subgroup analyses were performed to explore the heterogeneity of different therapies. Results: A total of 24 articles comprising 6318 patients were included in the meta-analysis. Overall, the pooled outcomes revealed that a high NLR before treatment predicted a poor OS (HR: 1.54, 95% CI: 1.34 to 1.76, p<0.001) and poor RFS (HR: 1.45, 95% CI: 1.16 to 1.82, p=0.001). Moreover, an increased PLR predicted a poor OS (HR: 1.63, 95% CI: 1.34 to 1.98, p<0.001) and earlier HCC recurrence (HR: 1.52, 95% CI: 1.21 to 1.91, p<0.001). In addition, both the NLR and PLR were identified as independent risk factors for predicting OS and RFS in HCC patients in a subgroup analysis of different treatment types, including curative or palliative therapy; however, these results were not found in the sorafenib subgroup due to limited clinical research. Conclusion: An increased NLR or PLR indicated poor outcomes for patients with HCC. The NLR and PLR may be considered as reliable and inexpensive biomarkers for making clinical decisions regarding HCC treatment.

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Phosphorylation of p53 Serine 15 Is a Predictor of Survival for Patients with Hepatocellular Carcinoma

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2019/9015453 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Taewoo Yang ◽

Yegyun Choi ◽

Jae Won Joh ◽

Steve K. Cho ◽

Dae-Shick Kim ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Proliferating Cell Nuclear Antigen ◽

Prognostic Value ◽

Nuclear Antigen ◽

Survival Outcomes ◽

P53 Expression ◽

Immunohistochemical Markers ◽

Prognostic Utility ◽

Poor Outcomes ◽

Proliferating Cell

Background. Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with a poor prognosis. Several commonly investigated immunohistochemical markers in resected HCC have potential prognostic value, but the prognostic utility of p53 expression in HCC has remained elusive. Aim. To evaluate the prognostic value of p53 and p53 phosphorylation at serine 15 (p53 Ser15-P) in patients with HCC. Methods. Surgically resected tumors from 199 HCC patients were analyzed for p21, p53, p53 Ser15-P, and proliferating cell nuclear antigen (PCNA) expression using immunohistochemistry. Results. Stratifying by the expression of p53 Ser15-P (P = 0.016), but not by p53 (P = 0.301), revealed significantly different survival outcomes in patients with HCC. Moreover, our analysis demonstrated that patients who were PCNA-positive and p53 Ser15-P–negative had significantly worse survival outcomes (P = 0.001) than patients who were PCNA-positive and p53 Ser15-P–positive. Conclusions. P53 Ser15-P is associated with poor outcomes in patients with HCC, and this prognostic marker is useful for predicting the survival of patients with PCNA-positive HCC.

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Clinical impact of sarcopenia assessment in patients with hepatocellular carcinoma undergoing treatments

Journal of Gastroenterology ◽

10.1007/s00535-020-01711-w ◽

2020 ◽

Vol 55 (10) ◽

pp. 927-943 ◽

Cited By ~ 2

Author(s):

Giovanni Marasco ◽

Matteo Serenari ◽

Matteo Renzulli ◽

Luigina Vanessa Alemanni ◽

Benedetta Rossini ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Skeletal Muscle ◽

Muscle Mass ◽

Skeletal Muscle Mass ◽

Appropriate Treatment ◽

Risk Of Mortality ◽

Short And Long Term ◽

Poor Outcomes ◽

And Function

Abstract Changes in body composition are associated with poor outcomes in cancer patients including hepatocellular carcinoma (HCC). Sarcopenia, defined as the loss of skeletal muscle mass, quality and function, has been associated with a higher rate of complications and recurrences in patients with cirrhosis and HCC. The assessment of patient general status before HCC treatment, including the presence of sarcopenia, is a key-point for achieving therapy tolerability and to avoid short- and long-term complications leading to poor patients’ survival. Thus, we aimed to review the current literature evaluating the role of sarcopenia assessment related to HCC treatments and to critically provide the clinicians with the most recent and valuable evidence. As a result, sarcopenia can be predictive of poor outcomes in patients undergoing liver resection, transplantation and systemic therapies, offering the chance to clinicians to improve the muscular status of these patients, especially those with high-grade sarcopenia at high risk of mortality. Further studies are needed to clarify the predictive value of sarcopenia in other HCC treatment settings and to evaluate its role as an additional staging tool for identifying the most appropriate treatment. Besides, interventional studies aiming at increasing the skeletal muscle mass for reducing complications and increasing the survival in patients with HCC are needed.

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Prognostic Factors after Percutaneous Radiofrequency Ablation in the Treatment of Hepatocellular Carcinoma. Impact of Incomplete Ablation on Recurrence and Overall Survival Rates

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.274.pro ◽

2018 ◽

Vol 27 (4) ◽

pp. 399-407 ◽

Cited By ~ 4

Author(s):

Zeno Sparchez ◽

Tudor Mocan ◽

Pompilia Radu ◽

Lavinia Patricia Mocan ◽

Mihaela Sparchez ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Radiofrequency Ablation ◽

Local Recurrence ◽

Histological Grade ◽

Survival Rates ◽

Distant Recurrence ◽

Ethanol Injection ◽

Pugh Class ◽

Poor Outcomes ◽

Long Term Impact

Aims: To report on the long-term impact of tumor and non-tumor related parameters on local recurrence, distant recurrence and survival in patients with naïve or recurrent type hepatocellular carcinoma (HCC) treated by radiofrequency ablation (RFA).Methods: We performed 240 RFA sessions on 133 patients with 156 HCC nodules developed on a background of liver cirrhosis and analyzed the outcomes.Results: Contrast-enhanced ultrasound performed one month after RFA showed complete ablation in 119 out of 133 (89.65%) patients. With a median follow-up of 46 months, 3-, 5- and 7-year survival rates were 61.7%, 35.7%, and 22.6%, respectively. Previous ethanol injection and histological grade were significantly related to local tumor progression. Child-Pugh class, incomplete ablation, histological grade, previous ethanol injection, alpha-fetoprotein level before the treatment, and local recurrence were all significantly related to distant recurrence. Multivariate analysis demonstrated that age, Child-Pugh class, distant recurrence and multiple incomplete ablations were significantly related to survival.Conclusion: Radiofrequency ablation could be locally curative for HCC, resulting in a survival longer than 7 years. Previous ethanol injection and incomplete ablations were strongly associated with poor outcomes.

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Impact of Sarcopenia on Survival and Clinical Outcomes in Patients With Liver Cirrhosis

Frontiers in Nutrition ◽

10.3389/fnut.2021.766451 ◽

2021 ◽

Vol 8 ◽

Author(s):

Mirabela-Madalina Topan ◽

Ioan Sporea ◽

Mirela Dănilă ◽

Alina Popescu ◽

Ana-Maria Ghiuchici ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Portal Hypertension ◽

Handgrip Strength ◽

Survival Rates ◽

Infectious Complications ◽

Skeletal Muscle Index ◽

Class B ◽

Impact On Survival ◽

Poor Outcomes

Background: Sarcopenia is now recognized more and more as a biomarker with poor outcomes in cirrhotic patients.Aims: The purpose of this study was to investigate the prevalence of sarcopenia in patients with liver cirrhosis and prospectively investigate the association between sarcopenia and different complications and its impact on survival.Material and Methods: This prospective study included patients with liver cirrhosis admitted to our department from 2018 to 2020. Sarcopenia was assessed according to EWGSOP2 criteria, incorporating low Handgrip strength (<27 kg for men and <16 kg for women) with low skeletal muscle index evaluated by CT (<50 for men and <39 for women). Associations between sarcopenia and portal hypertension-related complications, infectious complications, and risk of hepatocellular carcinoma, the number of in-hospital days, 30-day readmission, and survival over the next 6 and 12 months were analyzed.Results: A total of 201 patients were enrolled in the study, 63.2% male, mean age 61.65 ± 9.49 years, 79.6% Child-Pugh class B and C. The primary etiology of liver cirrhosis was alcohol consumption (55.2%). The prevalence of sarcopenia was 57.2 %, with no significant differences between the male and female groups. Significant associations were found between sarcopenia and portal hypertension-related complications, infectious complications, and risk of hepatocellular carcinoma. In multivariate analysis, sarcopenia was assessed as a risk factor alone, increasing the risk for ascites 3.78 times, hepatocellular carcinoma by 9.23 times, urinary tract infection by 4.83 times, and spontaneous peritonitis 2.49 times. Sarcopenia was associated with more extended hospital stay and higher 30 days readmission. Six months and 1-year survival were reduced in the sarcopenia group than in the non-sarcopenia group (p < 0.0001).Conclusion: Sarcopenia is a common complication of liver cirrhosis and associates with adverse health-related outcomes and poor survival rates.

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Overexpression of LGR-5 as a Predictor of Poor Outcome in Patients with Hepatocellular Carcinoma

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16101836 ◽

2019 ◽

Vol 16 (10) ◽

pp. 1836 ◽

Cited By ~ 3

Author(s):

Chih-Jan Ko ◽

Chia-Jung Li ◽

Meng-Yu Wu ◽

Pei-Yi Chu

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Development ◽

Normal Liver ◽

Leucine Rich Repeat ◽

Tumor Tissues ◽

B Virus ◽

Cell Signal Transduction ◽

Poor Outcomes ◽

Positive Groups ◽

G Protein Coupled

Hepatocarcinogenesis and distant metastasis pose major challenges for physicians. They are regulated by several genes, such as AKT, JUK, Wnt, and P53, and their expression activates several important processes such as cell proliferation, migration, motility, and interaction in the microenvironment. The leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR-5) is a novel biomarker, particularly in stem cells, and is involved in embryogenesis, tumor development, and tumor cell signal transduction. Here, we investigated LGR-5 expression using immunohistochemistry and analyzed the correlation between clinical features and prognosis in patients with hepatocellular carcinoma (HCC). We found that LGR-5 expression was higher in tumor tissues than in normal liver tissues, and that high LGR-5 expression possibly favored poor outcomes in HCC, especially in well/moderate differentiation grade, hepatitis C virus (HCV)-negative, and hepatitis B virus (HBV)-positive groups. Thus, the LGR-5 marker is suggested to be a routine biomarker for poor prognosis, thereby providing a platform for anti-LGR-5-targeted therapy in the future.

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