scholarly journals Serum Irisin Predicts Posthepatectomy Complications in Patients with Hepatocellular Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Jia Zhang ◽  
Mengyun Ke ◽  
Yifan Ren ◽  
Jianbin Bi ◽  
Zhaoqing Du ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rank Correlation ◽  
The Cancer Genome Atlas ◽  
Comprehensive Complication Index ◽  
Preoperative Serum ◽  
Fibronectin Type Iii ◽  
Tcga Dataset ◽  
Fibronectin Type Iii Domain

Background. Hepatectomy remains one of the most effective treatments for patients with hepatocellular carcinoma (HCC); however, it can lead to serious complications. Irisin, a key regulator of energy metabolism, is secreted into the circulation by shedding of the extracellular portion of the fibronectin type III domain-containing 5 (FNDC5). We have shown that irisin administration alleviates liver ischemia-reperfusion injury in mice. However, the role of preoperative irisin levels in HCC patients who underwent hepatectomy remained unknown. The purpose of this study was to determine how irisin expression changes in HCC and to explore the relationship between preoperative serum irisin levels and complications after hepatectomy. Methods. FNDC5/irisin expression data in HCC were extracted from The Cancer Genome Atlas (TCGA) dataset. A total of 219 participants, including 102 healthy controls and 117 HCC patients, were recruited in this study. All HCC patients underwent hepatectomy at the First Affiliated Hospital of the Xi’an Jiaotong University. Preoperative serum irisin levels were measured by ELISA. Postoperative complications were assessed using the comprehensive complication index (CCI) score. The Pearson rank correlation coefficient was computed to assess the correlation between preoperative serum irisin levels and postoperative CCI scores. Results. In TCGA dataset, FNDC5/irisin expression was downregulated in HCC tissues (P<0.001). Similarly, serum irisin levels were decreased in HCC patients (P<0.001). Low preoperative serum irisin levels were significantly correlated with high CCI scores after hepatectomy. Conclusions. Irisin may be a novel serum biomarker in the diagnosis of HCC and a predictor of complications after hepatectomy.

scholarly journals The Emerging Role of Irisin in Cardiovascular Diseases

2021 ◽  
Author(s):  
Jinjuan Fu ◽  
Fangtang Li ◽  
Yuanjuan Tang ◽  
Lin Cai ◽  
Chunyu Zeng ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Fibronectin Type Iii ◽  
Artery Disease ◽  
Myocardial Ischemia Reperfusion ◽  
Membrane Spanning ◽  
Fibronectin Type Iii Domain ◽  
Insulin Use

Abstract Irisin, a novel hormone like polypeptide, is cleaved and secreted by an unknown protease from a membrane‐spanning protein, FNDC5 (fibronectin type III domain‐containing protein 5). The current knowledge on the biological functions of irisin includes browning white adipose tissue, regulating insulin use, and anti‐inflammatory and antioxidative properties. Dysfunction of irisin has shown to be involved in cardiovascular diseases such as hypertension, coronary artery disease, myocardial infarction, and myocardial ischemia–reperfusion injury. Moreover, irisin gene variants are also associated with cardiovascular diseases. In this review, we discuss the current knowledge on irisin‐mediated regulatory mechanisms and their roles in the pathogenesis of cardiovascular diseases.

scholarly journals Irisin: A Promising Target for Ischemia-Reperfusion Injury Therapy

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Yani Wang ◽  
Huibin Liu ◽  
Na Sun ◽  
Jing Li ◽  
Xiang Peng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Beneficial Effects ◽  
Promising Target ◽  
Fibronectin Type Iii ◽  
Potential Benefits ◽  
Fibronectin Type Iii Domain ◽  
Fibronectin Type

Ischemia-reperfusion injury (IRI) is defined as the total combined damage that occurs during a period of ischemia and following the recovery of blood flow. Oxidative stress, mitochondrial dysfunction, and an inflammatory response are factors contributing to IRI-related damage that can each result in cell death. Irisin is a polypeptide that is proteolytically cleaved from the extracellular domain of fibronectin type III domain-containing protein 5 (FNDC5). Irisin acts as a myokine that potentially mediates beneficial effects of exercise by reducing oxidative stress, improving mitochondrial fitness, and suppressing inflammation. The existing literature also suggests a possible link between irisin and IRI, involving mechanisms similar to those associated with exercise. This article will review the pathogenesis of IRI and the potential benefits and current limitations of irisin as a therapeutic strategy for IRI, while highlighting the mechanistic correlations between irisin and IRI.

scholarly journals Alterations of Methionine Metabolism as Potential Targets for the Prevention and Therapy of Hepatocellular Carcinoma

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 296 ◽  
Author(s):  
Pascale ◽  
Peitta ◽  
Simile ◽  
Feo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Ischemia Reperfusion Injury ◽  
Recent Observation ◽  
Ischemia Reperfusion ◽  
Liver Steatosis ◽  
No Production ◽  
Hepatic Ischemia ◽  
Chronic Hepatitis B Virus ◽  
Methionine Cycle

Several researchers have analyzed the alterations of the methionine cycle associated with liver disease to clarify the pathogenesis of human hepatocellular carcinoma (HCC) and improve the preventive and the therapeutic approaches to this tumor. Different alterations of the methionine cycle leading to a decrease of S-adenosylmethionine (SAM) occur in hepatitis, liver steatosis, liver cirrhosis, and HCC. The reproduction of these changes in MAT1A-KO mice, prone to develop hepatitis and HCC, demonstrates the pathogenetic role of MAT1A gene under-regulation associated with up-regulation of the MAT2A gene (MAT1A:MAT2A switch), encoding the SAM synthesizing enzymes, methyladenosyltransferase I/III (MATI/III) and methyladenosyltransferase II (MATII), respectively. This leads to a rise of MATII, inhibited by the reaction product, with a consequent decrease of SAM synthesis. Attempts to increase the SAM pool by injecting exogenous SAM have beneficial effects in experimental alcoholic and non-alcoholic steatohepatitis and hepatocarcinogenesis. Mechanisms involved in hepatocarcinogenesis inhibition by SAM include: (1) antioxidative effects due to inhibition of nitric oxide (NO•) production, a rise in reduced glutathione (GSH) synthesis, stabilization of the DNA repair protein Apurinic/Apyrimidinic Endonuclease 1 (APEX1); (2) inhibition of c-myc, H-ras, and K-ras expression, prevention of NF-kB activation, and induction of overexpression of the oncosuppressor PP2A gene; (3) an increase in expression of the ERK inhibitor DUSP1; (4) inhibition of PI3K/AKT expression and down-regulation of C/EBPα and UCA1 gene transcripts; (5) blocking LKB1/AMPK activation; (6) DNA and protein methylation. Different clinical trials have documented curative effects of SAM in alcoholic liver disease. Furthermore, SAM enhances the IFN-α antiviral activity and protects against hepatic ischemia-reperfusion injury during hepatectomy in HCC patients with chronic hepatitis B virus (HBV) infection. However, although SAM prevents experimental tumors, it is not curative against already established experimental and human HCCs. The recent observation that the inhibition of MAT2A and MAT2B expression by miRNAs leads to a rise of endogenous SAM and strong inhibition of cancer cell growth could open new perspectives to the treatment of HCC.

scholarly journals The Oncogenic Role of CENPA in Hepatocellular Carcinoma Development: Evidence from Bioinformatic Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuan Zhang ◽  
Lei Yang ◽  
Jia Shi ◽  
Yunfei Lu ◽  
Xiaorong Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Free Survival ◽  
Tcga Dataset ◽  
High Level

Objective. This study is aimed at investigating the predictive value of CENPA in hepatocellular carcinoma (HCC) development. Methods. Using integrated bioinformatic analysis, we evaluated the CENPA mRNA expression in tumor and adjacent tissues and correlated it with HCC survival and clinicopathological features. A Cox regression hazard model was also performed. Results. CENPA mRNA was significantly upregulated in tumor tissues compared with that in adjacent tissues, which were validated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) series (all P<0.01). In the Kaplan-Meier plotter platform, the high level of CENPA mRNA was significantly correlated with overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), and progression-free survival (PFS) in HCC patients (all log rank P<0.01). For validation in GSE14520 and pan-TCGA dataset, HCC patients with CNEPA mRNA overexpression had poor OS compared with those with low CENPA mRNA (log rank P=0.025 and P<0.0001, respectively), and those with high CENPA had poor DFS in TCGA (log rank P=0.0001). Additionally, CENPA mRNA were upregulated in HCC patients with alpha-fetoprotein (AFP) elevation, advanced TNM stage, larger tumor size, advanced AJCC stage, advanced pathology grade, and vascular invasion (all P<0.05). A Cox regression model including CENPA, OIP5, and AURKB could predict OS in HCC patients effectively (AUC=0.683). Conclusion. Overexpressed in tumors, CENPA might be an oncogenic factor in the development of HCC patients.

scholarly journals Identification of Protein Expression Changes in Hepatocellular Carcinoma through iTRAQ

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Yuanyuan Zhang ◽  
Xia Ying ◽  
Qian Zhao ◽  
Jinlu Ma ◽  
Dan Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Serum Levels ◽  
Serum Biomarkers ◽  
The Cancer Genome Atlas ◽  
Paraoxonase 1 ◽  
Serum Samples ◽  
Absolute Quantitation ◽  
Isobaric Tags ◽  
Tcga Dataset ◽  
Normal Controls

Background. Hepatocellular carcinoma (HCC) is a malignant tumor associated with a poor prognosis. Serum biomarkers of HCC have the potential to improve the diagnosis, provide a means to monitor the tumors, and predict their malignancy. Proteins that are expressed differentially between HCC patients and normal controls have the potential to be biomarkers. Method. Serum samples from 10 confirmed HCC patients and 10 controls were collected. The differentially expressed proteins in the serum were identified using an isobaric tags for relative and absolute quantitation- (iTRAQ-) based method. Potential serum biomarkers were validated by ELISA in another 20 HCC patients and 20 controls. Their expression data in HCC were extracted from The Cancer Genome Atlas (TCGA) dataset. Results. A total of 260 proteins were measured in the serum of HCC patients and compared to those in sex- and age-matched normal controls. Forty-one proteins displayed significant changes, with 26 being downregulated and 15 being upregulated. Upregulated proteins included alpha-1-antitrypsin (A1AT) and peroxiredoxin 2 (PRDX2), and downregulated proteins included paraoxonase 1 (PON1) and C-reactive protein (CRP). We then used ELISA to measure serum levels of A1AT, PRDX2, PON1, and CRP in another 20 patients with HCC and found that only PON1 levels were consistent with the iTRAQ result. In TCGA dataset, PON1 expression was downregulated in HCC tissues (P<0.001) and low expression of PON1 was associated with poor survival in HCC patients (P<0.001). Conclusions. PON1 could act as a biomarker for HCC to assist in the diagnosis of HCC.

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