Implication of Long Non-coding RNA HOTTIP Haplotype
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 198
- 试验地点
- 1
- 主要终点
- Primary outcome
研究概览
简要总结
Hepatocellular carcinoma (HCC) represents the fourth common cancer and the most common cause of mortality-caused and morbidity-related cancer. Different reports implied several lncRNAs role in the progression and metastasis of HCC such as Homeobox A (HOXA) transcript at the distal tip (HOTTIP). Dysregulation of HOTTIP is associated with various malignancies including HCC, affecting survival and prognosis of cancer patients. HOTTIP promoted HCC cell proliferation/metastasis and might act as an oncogenic-lncRNA in HCC.
Genetic variations such as single-nucleotide polymorphisms (SNPs), when inherited together, as a group, known as haplotypes. Haplotypes can alter the expression of coding genes and the protein non-coding genes like lncRNAs, therefore, affecting the disease course, including liver, a hypothesis to be addressed.
Only few studies have focused on the polymorphisms of the onco-lncRNA HOTTIP gene. A study found that specific HOTTIP SNPs have the potential to be biomarkers for HCC risk and prognosis, where one haplotype of HOTTIP "rs17501292-rs2067087-rs17427960" showed a 1.91-fold increased risk of HCC.
详细描述
- Introduction Hepatocellular carcinoma HCC is a complex disease, which could be caused by viruses as hepatitis B and C infection, drug abuse, and chemicals such as aflatoxin. However, treatments for HCC are limited, and most of them are only effective at an early stage. At an advanced stage, this cancer is associated with a poor prognosis, due to frequent cancer metastasis, tumor recurrence and a lack of curative treatment. Different reports implied several lncRNAs role in the progression and metastasis of HCC such as HOXA transcript at the distal tip (HOTTIP). HOTTIP might act as an oncogenic-lncRNA in HCC.
Genetic variations such as single-nucleotide polymorphisms (SNPs), when inherited together, as a group, because of high Linkage Disequilibrium (LD), there tends to be redundant information. The regions of the genome with high LD, that harbor a specific set of SNPs, are inherited together, known as haplotypes. Haplotypes can alter the expression of coding genes and the protein non-coding genes like lncRNAs.
Only few studies have focused on the polymorphisms of the onco-lncRNA HOTTIP gene. A recent study found that specific HOTTIP SNPs have the potential to be biomarkers for HCC risk and prognosis, where one haplotype of HOTTIP gene "rs17501292-rs2067087-rs17427960" showed a 1.91-fold increased risk of HCC (P = 0.006) in Chinese patients' samples.
.............. 2. Objectives 2.1. Genotype different haplotype SNPs of lncRNA HOTTIP in whole blood samples (Liquid biopsy) from metastatic HCC patients, and to be compared with sex and age-matched non-metastatic patients.
2.2. Correlate HCC clinicopathological characteristics (tumor stage and grade, tumor progression (TNM) and different clinical presentations as presence/absence of metastasis, and other classical clinico-pathological prognostic biomarkers such as α-fetoprotein (AFP), carcinoembryonic antigen (CEA), alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), International normalized ratio (INR), prothrombin concentration (PC), total bilirubin, Gamma-glutamyltransferase (GGT), and complete blood count (CBC), blood pressure, blood glucose level, serum insulin, and body mass index (BMI), c-reactive protein (CRP), albumin, blood urea nitrogen (BUN) and prognostic marker(s)/outcome to HOTTIP genotypes or different haplotype SNPs.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 35 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HCC patients attending the Faculty of Medicine, Ain Shams University Hospital, with 1:1 or 1:2 ratio for the HCC groups metastatic vs non metastatic HCC groups (according to clinical evidence/relevance and/or availability).
- •Group 1; non-metastatic HCC patients, Group 2; metastatic HCC patients, diagnosed with primary HCC receiving any type of therapy (neoadjuvant or radiotherapy).
- •Eligibility criterion are adult age and male/female 1:1 according to availability.
- •Criteria for HCC diagnosis following the ASU hospital role relying on AFP level and CT scan or the fine needle biopsy.
- •Groups to be matched socioeconomically, in age range, residence (case-controlled study).
排除标准
- •HCC patients who have history of liver transplantation, have other cancer types at the time of selection, presented by renal insufficiency, and thyroid dysfunction will be excluded from the study. Additionally, patients with incomplete data or histopathology diagnosis.
结局指标
主要结局
Primary outcome
时间窗: 29 months
By the end of the current study, investigators will have elucidated the association of polymorphisms of SNPs (rs17501292\& rs2067087) in the lncRNA HOTTIP with HCC metastasis risk by comparing the two group of patients together using logistic regression. Additionally, investigators will assess prognosis in metastatic and non-metastatic primary HCC patients in liquid biopsy samples by using APRI score as an indicator of the prognosis. Finally, by using Kaplan-Meier curve, the overall survival of each group will be compared and related with each SNP polymorph.
次要结局
未报告次要终点
研究者
Prof. Nadia M. Hamdy, Ph.D.
Professor of Biochemistry and Molecular Biology at Biochemistry department, Faculty of Pharmacy
Ain Shams University