This study aimed to evaluate the individual and combined diagnostic values of serum alpha-fetoprotein (AFP), des-gamma-carboxyprothrombin (DCP), glypican-3 (GPC3) and golgi protein 73 (GP73) in diagnosing hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Participants from Beijing YouAn Hospital were enrolled and divided into seven groups. Serum was collected and the levels of AFP, GPC3, GP73 and DCP were simultaneously measured with a protein array. Pearson's χ2 test was applied to compare the clinicopathological characteristics. Receiver operating characteristic (ROC) curves were used to analyse the diagnostic performance of the four markers.As a single biomarker for differentiating HCC from all controls, AFP had a larger area under the curve (AUC) (0.798, 95% CI (0.754-0.838) than the other biomarkers, with a sensitivity of 77.3% and a specificity of 71.1%. Among the other combinations, AFP plus GPC3 and DCP (0.871, 95% CI (0.833-0.903)) was the best at differentiating HCC from all controls. In discriminating very early stage and early stage HCC from all controls, the AUC of GPC3 (0.744, 95% CI (0.690-0.793); sensitivity 62.8%; specificity 83.3%) was better than that of AFP (0.723, 95% CI (0.668-0.774); sensitivity 67.3%; specificity 71.7%). Among all biomarker combinations, the combination of AFP, GPC3 and GP73 had the largest AUC (0.843, 95% CI (0.796-0.883); sensitivity 84.1%; specificity 71.7%). AFP (AUC 0.726, 95% CI (0.662-0.784)) showed the best performance in the very early diagnosis of HBV-related HCC.As a single biomarker, AFP has an advantage in the very early and early diagnosis of HBV-related HCC. The combination of AFP, GPC3 and GP73 is the most suitable marker for the early diagnosis of HBV-related HCC. However, AFP remains the best biomarker for the very early diagnosis of HBV-related HCC, and the adding of one or more markers does not significantly improve the diagnostic accuracy.
Increasing evidence has shown that abnormal expression of XPO5 is found in many human cancers and acts as an oncoprotein in certain cancers. However, its functional role in hepatocellular carcinoma (HCC) remains unexplored. In our study, we found that XPO5 was highly expressed in HCC, which was associated with SUMO modification. Moreover, we found that XPO5 was SUMOylated by SUMO2 at K125. Functional experiments revealed that XPO5 SUMOylation could promote MHCC97H cell proliferation, migration and invasion. In addition, we found that the nuclear export of pre-miR-3184 was suppressed by SUMOylated XPO5. Moreover, PLCB1 was identified as the common target of miR-3184-5p and miR-3184-3p. The suppressed phenotype induced by miR-3184-5p and miR-3184-3p could be rescued by overexpression of PLCB1. Bioinformatics analysis showed that PLCB1 expression had a negative relationship with HCC patient survival. The inhibitory effects of MHCC97H cells resulted from abnormal XPO5 SUMO modification could be blocked by miR-3184 inhibitor or PLCB1 overexpression. In conclusion, our findings demonstrate a novel mechanism of XPO5 in HCC, that is, the SUMOylated XPO5 acts as an "oncogenic" role in MHCC97H cells proliferation, migration and invasion by controlling the nuclear-cytoplasm transportation of miR-3184, thus up-regulating PLCB1 expression.
Hilar cholangiocarcinoma (HCC) is a rare tumor with a poor prognosis.With the development of high definition imaging technology,improvement of surgical instruments,optimization of perioperative surgical strategies and accumulation of surgical experiences,the radical resection rate of HCC is significantly improved.Operation is the main method of treatment for HCC,and radical resection is important for a long-term survival of HCC patients.The clinical data of 66 patients with HCC who were admitted to the Beijing Youan Hospital from April 2004 to April 2012 were retrospectively analyzed.The key points in surgical procedure and prognosis of patients were investigated.
Key words:
Cholangiocarcinoma, hilar ; Surgical procedures, operative
e16140 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies and leading cause of cancer deaths worldwide. Biomarkers contribute to predict the response of targeted treatments and immunotherapy. Therapy directed toward homologous recombination deficiency (HRD) is now approved in ovarian and breast cancer, but the pattern of HRD is not clear in HCC. The HRD phenotype has been defined as the presence of a non-silent somatic mutation in homologous recombination-related (HRR) genes. Thus, we aimed to analyze the molecular characteristics of resectable HCC, including HRR genes. Methods: Matched tumor/normal DNA from resectable HCC patients (N = 53) were analyzed by whole exome sequencing (WES) or Acornmed panel with 808 cancer-related genes. Results: Overall, 94.3% (50/53) patients exhibited genetic alterations. TP53, ARID1A, PTEN and NBPF1 were the most commonly mutated genes in resectable HCC. In addtion, 35.9% patinets harbored at least one HRR genes mutation. The frequently mutated genes were BRCA2 (4.4%), BRCA1(4.0%), ATM (3.9 %), and RAD50 (3.8%). Interesting, frequency of HRR genes mutation in the Chinese cohort was higher than that in TCGA (35.9 % vs 20.9%). Analysis of carcinogenic pathways shown that ERBB and PI3K-AKT signaling pathway were the common signaling pathway. In resectable HCC, 32.08% (17/53) patients disclosed high TMB (highest 25%). Further analysis found that PTEN mutations were remarkably associated with low TMB (p < 0.05). Conclusions: This study contributes to understand the molecular characteristics of patients with resectable HCC, which will be useful to guide personalized therapy and promote the clinical management in this population. Furthermore, the study suggested that it is feasibility for resectable HCC patients received PARP inhibitors, DNA-damaging chemotherapies, and immune checkpoint blockade therapy.
Objectives This study aimed to examine a simple, effective, time-saving, and low-cost protein microarray method for detecting serum alpha-fetoprotein (AFP) and AFP-L3 levels. Methods Serum samples from patients with hepatocellular carcinoma (HCC) (n = 33) and control subjects (n = 39) were collected and evaluated for the presence of AFP using a novel protein microarray. Glycoprotein (including AFP-L3) was enriched from crude samples by a Hotgen Biotech glycosyl capture spin column and then detected by protein microarray. An electrochemiluminescence immunoassay (ECLIA) was used to validate the measured values. Results Neither AFP levels lower than 20 ng/mL in the HCC group nor AFP levels higher than 20 ng/mL in the control group were found when tested by the ECLIA and protein microarray. The kappa test showed good consistency in the diagnostic performance of measuring serum AFP levels and the percentage of AFP-L3 in total AFP by the ECLIA and protein microarray. Protein microarray had advantages of smaller sample size required, low cost, and convenience compared with the ECLIA. Conclusion The protein microarray assay that was developed in the present study shows potential as an economic and convenient technique for detecting AFP and AFP-L3 levels in serum samples from patients with HCC.
Hepatocellular carcinoma (HCC) is the major pathological type of primary liver cancer, one of the leading causes of cancer death worldwide. In addition, the long-term survival rates of HCC still remain low. Therefore, we attempted to identify the potential key genes in the occurrence of HCC by comparing the expression profiles of very early HCC tissue samples with that of chronic cirrhotic tissue samples by integrating the bioinformatics analysis in this study.Gene expression profiles of 19 very early HCC and 19 cirrhotic tissue samples were selected from GSE63898. Differentially expressed genes (DEGs) were also identified by using online tool GEO2R. Furthermore, the GO and KEGG enrichment analysis of the DGEs were conducted on DAVID datasets. Then a protein-protein interaction (PPI) network was constructed and the modules were analyzed based on STRING database and Cytoscape software. The hub genes were screened by applying the cytoHubba plugin and then analyzed with the Kaplan Meier plotter.A total of 118 DEGs were identified between very early HCC and cirrhotic tissue samples. These DGEs were strongly associated with several biological processes, such as negative regulation of growth and p53 signaling pathway. A PPI network was constructed and top eight hub genes, including CDKN3, CDK1, CCNB1, TOP2A, CCNA2, CCNB2, PRC1, and RRM2, were determined. High expressions of CDK1, CCNB1, TOP2A, CCNA2, PRC1, RRM2, CDKN3, and CCNB2 were associated with poorer overall survivals (OS) in HCC patients.We had compared the expression profiles between the very early HCC and cirrhotic tissue samples by using bioinformatics analysis tools, which might help us better to understand the molecular mechanism of the initiation of HCC and even to find novel targets for HCC therapy.
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