Feiguo Zhou

Association of a variant in MIR 196A2 with susceptibility to hepatocellular carcinoma in male Chinese patients with chronic hepatitis B virus infection.

MicroRNAs (miRNAs) are small noncoding RNAs with regulatory functions as tumor suppressors and oncogenes. Recent studies have implicated that the rs11614913 SNP in MIR196A2 was associated with susceptibility of lung cancer, congenital heart disease, breast cancer and shortened survival time of nonsmall cell lung cancer. To assess whether this polymorphism is associated with susceptibility to and clinicopathologic characteristics of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), a total of 560 patients with chronic HBV infection and 391 healthy volunteers were enrolled, and MIR196A2 polymorphism was genotyped by polymerase chain reaction-ligation detection reaction (PCR-LDR). In our study group, there was no significant association between MIR196A2 polymorphism and the risk of HBV-related HCC in all subjects, however, the risk of HCC was significantly higher with MIR196A2 rs11614913 CC genotype or C allele compared with those with the TT genotype or T allele in male patients. Furthermore, in a subsequent analysis of the association between this polymorphism and clinicopathologic characteristics, there was still no significant difference in both the distribution of genotype or allelic frequency. However, we observed that the T allele was significantly more frequent in male HCC patients with lymphatic metastasis. Our results suggested that MIR196A2 polymorphism was associated with susceptibility to HBV-related HCC in a male Chinese population.

+49G > A polymorphism in the cytotoxic T-lymphocyte antigen-4 gene increases susceptibility to hepatitis B-related hepatocellular carcinoma in a male Chinese population.

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an important regulator and functions negatively in immune response. Its nonsynonymous polymorphism +49G > A (dbSNP: rs231775) has been linked to an elevated risk of T-cell-mediated autoimmune diseases, infectious diseases, and even carcinomas. Here, we examined the genotypes at rs231775 of 1003 subjects in a Han Chinese population to detect the association between this single-nucleotide polymorphism (SNP) and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) susceptibility, including 375 HBV-related HCC patients, 209 non-HCC patients with HBV infection, and 419 healthy controls. Our results indicated a weak trend for the relationship between rs231775 and HBV-related HCC susceptibility, although the statistical level was not significant. However, a significant difference was identified in males between HBV-related HCC patients and healthy controls. The data revealed that the frequency of the A/A genotype was higher in patients compared with healthy controls (odds ratio [OR] = 1.79, 95% confidence interval [95% CI] 1.05-3.08). The G allele appeared to have a protective effect in developing HBV-related HCC. Subjects with the A allele had higher HCC susceptibility than those with the G allele (OR = 1.31, 95% CI 1.03-1.66). These results suggested that the A/A genotype and A allele of rs231775 increased the risk of developing HBV-related HCC in a male Chinese population.

CTLA-4 +49A>G polymorphism is associated with the risk but not with the progression of colorectal cancer in Chinese

PurposeColorectal cancer (CRC) is one of the most common malignancies in the world and a multipathway disease. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by down-regulating T-cell activation. The most studied +49A>G polymorphism of CTLA-4 gene has been associated with several autoimmune or cancer diseases. Our aim was to investigate the association between this genetic variant and the risk as well as progression of colorectal cancer in Chinese.MethodsWe conducted a case–control study of 124 colorectal cancer cases and 407 healthy controls. DNA was extracted from blood specimens, and +49A>G polymorphism in the CTLA-4 gene was genotyped by polymerase chain reaction–ligation detection reaction (PCR–LDR).ResultsIn our study group, the frequency of AG or GG or carrying at least one G allele at position +49 was significantly different in colorectal cancer patients and the control group, indicating that the risk of CRC was significantly higher among subjects with the AG or GG genotype or carrying at least one G allele at position +49 than among the subjects with the AA genotype. However, we observed no association between CTLA-4 +49A>G polymorphism and the progression of CRC. Interestingly, the CTLA-4 +49A allele was in non-significantly higher numbers in CRC patients with distant metastasis.ConclusionsOur results suggested that CTLA-4 +49A>G polymorphism was associated with an increased risk of colorectal cancer, but this polymorphism did not play an important role in the progression of CRC in Chinese.

N-glycan based models improve diagnostic efficacies in hepatitis B virus-related hepatocellular carcinoma.

The early diagnosis of hepatocellular carcinoma (HCC) is of great clinical desirable due to lack of specific and sensitive markers. Alterations in the sugar chains of glycoprotein synthesized by the liver contribute to the molecular basis of abnormalities in carcinogenesis. This study aims to construct and assess the diagnostic value of N‐glycan based diagnostic model in HCC identification and follow‐up. A total of 393 subjects including HBV‐related HCC, liver fibrosis and healthy controls were recruited. Follow‐up was carried out before and after surgical treatment in HCC. N‐glycome of serum glycoprotein was profiled by DNA sequencer‐assisted fluorophore‐assisted carbohydrate electrophoresis (DSA‐FACE). Multiparameters diagnostic models were constructed based on N‐glycan markers. The result found that 2 N‐glycan structure abundances (NG1A2F, Peak 4; NA3Fb, Peak 9) were useful as N‐glycan markers. The diagnostic efficacy of the log ratio [log(p9/4)] was similar to that of AFP in differentiating HCC from fibrosis. The accuracy and sensitivity of the diagnostic model combining AFP and N‐glycan markers (Cscore B) were increased 7–10% compared with that of AFP. Log(p9/4) was more efficient in monitoring the progression of HCC with regarding to vascular invasion at improved specificity (16%) and accuracy (8%) compared with that of AFP. The N‐glycan markers were found to be changed significantly after surgical resection in HCC follow‐up. We conclude that the branching α (1,3)‐fucosylated triantennary glycan and a biantennary glycan are promising as N‐glycan markers. The diagnostic models based on the N‐glycan markers and AFP improve the efficacy in HCC diagnosis and progression monitoring.

Diagnostic Evaluation of Des-Gamma-Carboxy Prothrombin versus α-Fetoprotein for Hepatitis B Virus-Related Hepatocellular Carcinoma in China: A Large-Scale, Multicentre Study.

An efficient serum marker for hepatocellular carcinoma (HCC) is currently lacking and requires intensive exploration. We aimed to evaluate the performance of des-gamma-carboxy prothrombin (DCP) for identifying hepatitis B virus-related HCC in a large, multicentre study in China. A total of 1034 subjects in three cohorts (A, B, and C) including HCC and various non-HCC controls were enrolled from 4 academic medical centers in China from January 2011 to February 2014. Blind parallel detections were conducted for DCP and AFP. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacies. In cohort A, which comprised 521 subjects, including patients with HCC, liver metastasis, liver cirrhosis (LC), and liver hemangiomas as well as healthy controls (HCs), the accuracy of DCP for distinguishing HCC from various controls was 6.2–9.7% higher than that of AFP. In cohort B, which comprised 447 subjects, including patients with HCC, LC, and chronic hepatitis B as well as HC, the accuracy of DCP was further elevated (12.3–20.67% higher than that of AFP). The superiority of DCP to AFP was more profound in the surveillance of early HCC [AUC 0.837 (95% CI: 0.771–0.903) vs. 0.650 (0.555–0.745)] and AFP-negative HCC [AUC: 0.856 (0.798–0.914)] and in discriminating HCC from LC (accuracy: 92.9% vs.64.71%). Higher DCP levels were associated with worse clinical behaviors and shorter disease-free survival. DCP not only is complementary to AFP in identifying AFP-negative HCC and in excluding AFP-positive non-HCC (liver cirrhosis), but also demonstrates improved performance in HCC surveillance, early diagnosis, treatment response and recurrence monitoring in the HBV-related population.

−509C>T polymorphism in the TGF-β1 gene promoter is not associated with susceptibility to and progression of colorectal cancer in Chinese

Aim  Colorectal cancer is common, accounting for nearly 10% of all cancers. Transforming growth factor‐β1 (TGF‐β1) is a pleiotropic cytokine that has been implicated in the pathogenesis of colorectal neoplasia. The most studied −509C>T polymorphism of TGF‐β1 gene has been associated with various kinds of cancer. This study investigated the association between this genetic variant and the risk and/or progression of colorectal cancer.

Elevated core-fucosylated IgG is a new marker for hepatitis B virus-related hepatocellular carcinoma.

Immunoglubulin G (IgG) and its abnormal glycosylations are associated with carcinogenesis. The present study investigates the relationship between cancer-derived IgG and clinicopathological characteristics in hepatocellular carcinoma (HCC) and assesses the value of serum N-glycosylated IgG in diagnosing and monitoring hepatitis B virus (HBV)-related HCC. Tissue microarray analysis of 90 HCC tissues showed that HCC patients with IgG immunopositivity had higher levels of core-fucosylated α fetoprotein (AFP-L3), larger tumors, and a higher incidence of portal vein tumor thrombus. HCC-derived IgG stimulated the growth of liver cancer cells in vitro. HCC patients presented a significantly increased fraction of Lens culinaris agglutinin binding IgG (core-fucosylated IgG, IgG-L3) among total serum IgG. The clinical diagnostic performance of serum IgG-L3% was evaluated in 3 case-control studies (1 training set and 2 validation cohorts), including 293 patients with HCC, 131 with liver cirrhosis, 132 HBV carriers, and 151 healthy controls. IgG-L3% had better general diagnostic performance than AFP in the training set and validation cohort 1 (accuracy: 81.33–85.11% versus 63.33–78.61%). In validation cohort 2, where we aimed to assess the efficiency of IgG-L3% in patients with AFP-negative HCC, the diagnostic accuracy of IgG-L3% was 72.54–73.60%. Finally, a longitudinal evaluation based on 31 HCC patients demonstrated that IgG-L3% decreased in 24 patients after curative surgery. The remaining 7 patients showed elevated IgG-L3% and post-operative recurrence. HCC patients with higher IgG-L3% had poor survival during a 3-year follow up. We conclude that HCC-derived IgG is correlated with progressive behavior of HCC. Therefore, elevated core-fucosylated IgG is a new diagnostic and prognostic marker in HBV-related HCC.