Biologic Basis of Liver Cancer From Chronic Hepatitis B
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Associate viral sequences and host gene expression signatures with established HCC risk factors in Asian Americans.
研究概览
简要总结
The focus of the study is to identify viral factors and host immune responses that differentiate HBV-related HCC patients from HBV patients who have not progressed to HCC. To that end, the investigators will compare gene expression levels between HCC patients and non-HCC patients categorized into high and low risk profiles. The investigators will perform ANOVA to compare three groups (HCC, high risk, low risk). Multiple comparison corrections will be performed using Benjamini and Hochberg False Discovery Rate (FDR) with a 90% confidence that the discovery lists will contain no more than 5% false positives (FDR<0.05) (PMID: 12584122, 11682119). A p-value <0.05 is considered statistically significant using this multiple comparison correction approach. Post-hoc Student-Newman-Keuls or Tukey tests will be used following ANOVA for comparisons of HCC patients with high risk and low risk. If data are not normally distributed when log-transformed, then Kruskall-Wallis tests will be used. ANCOVA will be used to adjust for the effects of covariates, such as age, gender, and HBV genotype (B or C). Further, the investigators often use an additional 2-fold change criterion for significance because the investigators consider a fold change of this magnitude to be biologically significant. Hierarchical clustering analyses and principal component analyses will be used to visualize how well the genes separate the groups, or to discover new subgroups. For the analysis of SNVs, the exact binomial test will be performed and p-values will be adjusted by the Benjamini-Hochberg correction.
详细描述
- Objectives
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide (Jemel et al CA Cancer J Clin 2011). Asian and Pacific Islander (API) Americans are perennially the most affected racial group with regard to HCC incidence and HCC-related mortality due to the high prevalence of chronic hepatitis B (CHB). While APIs carry the greatest burden of CHB-related HCC, differences in outcome exist amongst the different Asian ethnic groups. The investigators have previously analyzed ethnically disaggregated data from 6,068 Californians of Asian ancestry with HCC diagnosed between 1998 and 2007 (Ryerson et al Cancer 2016). Cause-specific mortality was significantly higher among Laotian/Hmong (hazard ratio, 2.08; 95% CI, 1.78-2.44) and Cambodian patients (hazard ratio 1.26; 95% CI, 1.06-1.51). Notably, Laotian/Hmong patients presented at an early age and with more advanced stages of HCC suggesting that these differences were not related to delays in diagnosis or presentation, but rather biologic differences in the behavior of the HCC. In fact, both viral factors and host immune responses have been associated with the prognosis of CHB-related HCC. Currently, the investigators are investigating these potential mechanisms in Hmong/Laotian, Chinese, and Vietnamese individuals infected with the hepatitis B virus (HBV). In contrast to evaluating mechanisms associated with poor outcomes once HCC has developed, the current proposal will build upon the data the investigators have collected with the goal to identify markers of HCC development.
Central hypothesis is that prior to the development of HBV-related HCC, there are specific biologic responses reflected in the gene expression profile of whole blood that can differentiate CHB patients with and without HCC.
In order to test this hypothesis the investigators will perform the following specific aims:
Part 1 (Aim #1): Associate viral sequences and host gene expression signatures with established HCC risk factors in Asian Americans.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Asian Americans
- •Aged 18 years or older with a confirmed diagnosis of HCC and liver cancer from chronic hepatitis B.
- •The diagnosis of liver cancer can be made with by meeting radiologic criteria for HCC or liver histology obtained through liver biopsy.
排除标准
- •Co-infection with hepatitis C virus (HCV) or HIV
- •Use of immunosuppressive medications
- •Inability to give informed consent
- •Pregnant women
- •Cognitively impaired individuals or inability to provide informed consent
结局指标
主要结局
Associate viral sequences and host gene expression signatures with established HCC risk factors in Asian Americans.
时间窗: 1 year
In order to meet this aim, blood samples will be obtained from 10 consented subjects. The DNA extracted from these samples will be used as part of an ongoing study comparing viral sequences and gene expression profiles across Asian ethnic groups, we will analyze the same data comparing individuals with high and low HCC risk factors (i.e. the presence and absence of cirrhosis, high HBV viral load, men who have sex with men).
次要结局
未报告次要终点