Identification of potential prognostic biomarkers for hepatocellular carcinoma

BackgroundThe incidence of liver cancer is increasing every year. Hepatocellular carcinoma (HCC) accounts for nearly 90% of liver cancer, and the overall 5-year survival rate of become of Hepatocellular carcinoma patients less than 20%. However, the molecular mechanism of HCC progression and prognosis still requires further exploration.MethodsIn this study, we downloaded the gene expression data from the Cancer Genome Atlas (TCGA) Genomic Data and the official website of GEO database. Weighted gene co-expression network analysis (WGCNA) and Pearson’s correlation coefficient were utilized to detect the gene modules. The shared differentially-expressed genes (DEGs) were screened out by a Venn diagram, and the hub genes were identified through protein-protein interaction (PPI) network analyses. GO and KEGG enrichment analyses were constructed for these hub genes. Overall survival (OS) and correlation analysis were conducted to investigate the relationship between the hub genes and clinical features.ResultsWe screened out 27 shared DEGs, and the mainly enriched GO terms were mitotic nuclear division, chromosomal region, and tubulin binding. Furthermore, the top three enriched KEGG pathways were “cell cycle”, “oocyte meiosis”, and “p53 signaling pathway”. According to the Maximal Clique Centrality (MCC) algorithm, the top 10 candidate hub genes were MYC, MCM3, CDC20, CCNB1, BIRC5, UBE2C, TOP2A, RRM2, TK1, and PTTG1, among which BIRC5, CDC20, and UBE2C showed a strong correlation with the OS.ConclusionsThree hub genes (BIRC5, CDC20, and UBE2C) were identified and found to be correlated to the progression and prognosis of HCC. These may become potential targets for HCC therapy.     

Prediction of early recurrence of hepatocellular carcinoma after resection based on Gd-EOB-DTPA enhanced magnetic resonance imaging: a preliminary study

BackgroundEarly recurrence (ER) after radical resection of hepatocellular carcinoma (HCC) affects the prognosis of patients. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) can improve the detection rate of small HCC. This study innovatively introduces a new quantitative index combined with qualitative index to compare the differences in clinical and imaging characteristics between ER and non-ER groups and evaluate the feasibility of Gd-EOB-DTPA-enhanced MRI in predicting ER.MethodsA total of 68 patients with HCC confirmed by operation and pathology in the Shandong Cancer Hospital and Institute were included retrospectively. All participants were examined by Gd-EOB-DTPA-enhanced MRI within 3 weeks before surgery. Regular follow-up was performed every 2 months within 1 year after operation. Among them, 18 cases with new lesions were in ER group, and 50 cases without new lesions were in non-ER group. The clinical and imaging data of the 2 groups were collected, and the differences of clinical data and preoperative MRI signs between the ER group and non-ER group were compared. The predictive factors of ER after HCC were analyzed by multivariate logistic regression.ResultsThe quantitative parameter lesion-to-liver contrast enhancement ratio (LLCER) can predict the pathological grade of HCC (P=0.023). The results of univariate analysis between the ER group and non-ER group showed that there were significant differences in pathological grade (P=0.008), lesion morphology (P=0.011), peritumoral low signal intensity in hepatobiliary phase (HBP) (P<0.001), satellite nodules (P<0.001), and LLCER (P<0.001) between the 2 groups. Multivariate logistic regression analysis showed that HBP peritumoral low signal intensity [odds ratio (OR) =7.214, 95% confidence interval (CI): 1.230–42.312, P=0.029], satellite nodules (OR =9.198, 95% CI: 1.402–60.339, P=0.021), and parameter LLCER value (OR =0.906, 95% CI: 0.826–0.995, P=0.039) were independent predictors of ER of HCC after resection.ConclusionsPreoperative Gd-EOB-DTPA enhanced MRI has important predictive value for early recurrence after radical resection of hepatocellular carcinoma.     

TTV与HBV、HCV的重叠感染与HCC家庭聚集性的关系研究

目的:探讨广西肝癌高发区输血传播病毒(TTV)与乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)的重叠感染在原发性肝细胞癌(HCC)家庭聚集性中的作用.方法:分别采用巢式PCR和RT-PCR技术对研究对象外周血清中TTVDNA、HBVDNA和HCVRNA进行检测,应用χ2检验进行统计学分析.结果:HCC高发家庭成员组及无癌家庭成员组中TTVDNA、HBV DNA、HCVRNA阳性率分别为35.4%(46/130)、29.2%(38/130)、10.0%(13/130)和 24.6%(32/130)、10.8%(14/130)、3.8%(5/130),两组间TTVDNA、HBVDNA、HCVRNA阳性率差异有统计学意义(χ2=4.12、P=0.04、RR=1.81、95%CI=1.018～3.219;χ2=14.97、P=0.000 1、RR=3.765、95%CI=1.88～7.54;χ2=3.91、P=0.048、RR=2.84、95%CI=0.972～8.29).两组TTV与HBV、HCV重叠感染率分别为7.7%(10/130)、3.8%(5/130)和1.5%(2/130)、1.5%(2/130),TTVDNA HBVDNA感染率在两组间差异有统计学意义(χ2= 5.591 4、P=0.018 0、RR=5.33、95%CI=1.15～24.84);而TTVDNA HCVRNA阳性率在两组间差异无统计学意义(χ2=1.321 3、P=0.250 4、RR=2.56、95%CI=0.49～13.44).结论:TTV、HBV、HCV感染以及TTV和HBV的重叠感染与广西HCC家庭聚集性存在一定的相关关系,但 TTV和HBV重叠感染在致肝癌上无明显协同作用.     

Disruption of beta-catenin pathway or genomic instability define two distinct categories of liver cancer in transgenic mice

BACKGROUND & AIMS: Human liver cancer can be divided into 2 categories that are characterized by activation of beta-catenin and genomic instability. Here we investigate whether similar categories exist among 5 transgenic models of liver cancer, including c-myc, transforming growth factor-alpha, E2F-1, c-myc/transforming growth factor-alpha, and c-myc/E2F-1 mice. METHODS: The random amplified polymorphic DNA method was used to assess the overall genomic instability, and chromosomal loci affected by genomic alterations were determined by microsatellite analysis. beta-Catenin mutations and deletions were analyzed by polymerase chain reaction and sequencing screening. Cellular localization of beta-catenin and expression of alpha-fetoprotein, a prognostic marker of hepatocellular carcinoma, were investigated by immunohistochemistry. RESULTS: Liver tumors from the transgenic mice could be divided into 2 broad categories characterized by extensive genomic instability (exemplified by the c-myc/transforming growth factor-alpha mouse) and activation of beta-catenin (exemplified by the c-myc/E2F-1 mouse). The c-myc/transforming growth factor-alpha tumors displayed extensive genomic instability with recurrent loss of heterozygosity at chromosomes 1, 2, 4, 6, 7, 9, 12, 14, and X and a low rate of beta-catenin activation. The genomic instability was evident from the early dysplastic stage and occurred concomitantly with increased expression of alpha-fetoprotein. The c-myc/E2F-1 tumors were characterized by a high frequency of beta-catenin activation in the presence of a relatively stable genome and low alpha-fetoprotein levels. CONCLUSIONS: We have identified 2 prototype experimental models, i.e., c-myc/transforming growth factor-alpha and c-myc/E2F-1 mice, for the 2 categories of human hepatocellular carcinoma characterized by genomic instability and beta-catenin activation, respectively. These mouse models will assist in the elucidation of the molecular basis of human hepatocellular carcinoma.     

自然杀伤细胞抗肝癌的研究新进展

肝癌是最常见的恶性肿瘤之一,预后差,复发率高。免疫治疗已成为继手术、放疗、化疗后的第四种治疗模式,其中自然杀伤细胞可以在细胞、分子及基因水平抑制肿瘤转移及复发,在肝癌的免疫治疗中起关键性作用,在开展新的治疗模式以及提高肝癌患者生活质量方面具有很广阔的应用前景。     

Characterization of SCCA-IgM as a biomarker of liver disease in an Asian cohort of patients

Viral hepatitis infection is a major global issue and a leading cause of liver disease and associated deaths. Over time, patients infected with hepatitis B (HBV) or C virus (HCV) develop cirrhosis and, eventually, hepatocellular carcinoma (HCC). For this reason, they need to be constantly monitored. Current Asian guidelines recommend the determination of serum alpha-fetoprotein (AFP) together with liver ultrasounds every six months to detect HCC nodules. However, both methods have several limitations, and other biomarkers have been studied for monitoring cirrhosis, including SCCA-IgM, an immune-complex formed by Squamous Cell Carcinoma Antigen and IgM. To date, SCCA-IgM has been validated as a novel biomarker for liver diseases only in European populations. The aim of our study was to analyze SCCA-IgM as a biomarker to monitor cirrhosis evolution in an Asian cohort of patients and to compare its performance to that of AFP. We analyzed the concentration of AFP and SCCA-IgM in serum samples obtained from a group of Asian adult patients with cirrhosis or HCC and a control group of patients admitted for gastrointestinal disorders. In untreated patients and similarly to AFP, SCCA-IgM levels were significantly higher in patients with cirrhosis compared to those with HCC. In addition, SCCA-IgM, but not AFP serological levels, were significantly lower in HCC patients who were treated with surgical resection compared to those who received a different therapy.     

BAP1 mutations define a homogeneous subgroup of hepatocellular carcinoma with fibrolamellar-like features and activated PKA

1. Download : Download high-res image (262KB)
2. Download : Download full-size image

     

Mechanisms of Action and Resistance of Somatostatin Analogues for the Treatment of Hepatocellular Carcinoma: A Message Not Well Taken

Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated.