Implication of Long Non-coding RNA HOTTIP Haplotype on Liver Cancer Metastasis

NCT06544005 | Completed

• 1 other identifier: RHDIRB2020110301REC#70
• Study Type: observational
• Target: 198
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Keywords

HCC; HOTTIP; SNPs; Haplotype; Survival

Outcome Measures

Primary Outcomes (1)

• Primary outcome

  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.

  29 months

Study Arms (2)

Non-metastatic HCC group

129 HCC patients attending the Faculty of Medicine, Ain Shams University Hospital, males and females (according to availability), diagnosed with primary HCC receiving any type of therapy (neoadjuvant or radiotherapy). 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.

Metastatic HCC group

69 HCC patients attending the Faculty of Medicine, Ain Shams University Hospital, males and females (according to availability), diagnosed with primary HCC receiving any type of therapy (neoadjuvant or radiotherapy). 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.

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The patients enrolled in this study if they met the inclusion criteria and after giving their approval for participation in the study, signed the informed consent.

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Faculty of Pharmacy, Ain Shams Univeristy, Advanced Biochemistry Research Lab.

Cairo, Egypt

Location

Related Publications (12)

• Rashed WM, Kandeil MAM, Mahmoud MO, Ezzat S. Hepatocellular Carcinoma (HCC) in Egypt: A comprehensive overview. J Egypt Natl Canc Inst. 2020 Jan 16;32(1):5. doi: 10.1186/s43046-020-0016-x.

  PMID: 32372179 BACKGROUND

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• George J, Patel T. Noncoding RNA as therapeutic targets for hepatocellular carcinoma. Semin Liver Dis. 2015 Feb;35(1):63-74. doi: 10.1055/s-0034-1397350. Epub 2015 Jan 29.

  PMID: 25632936 BACKGROUND

• Tsang FH, Au SL, Wei L, Fan DN, Lee JM, Wong CC, Ng IO, Wong CM. Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b. Liver Int. 2015 May;35(5):1597-606. doi: 10.1111/liv.12746. Epub 2015 Jan 27.

  PMID: 25424744 BACKGROUND

• Lian Y, Cai Z, Gong H, Xue S, Wu D, Wang K. HOTTIP: a critical oncogenic long non-coding RNA in human cancers. Mol Biosyst. 2016 Oct 18;12(11):3247-3253. doi: 10.1039/c6mb00475j.

  PMID: 27546609 BACKGROUND

• Dong SS, He WM, Ji JJ, Zhang C, Guo Y, Yang TL. LDBlockShow: a fast and convenient tool for visualizing linkage disequilibrium and haplotype blocks based on variant call format files. Brief Bioinform. 2021 Jul 20;22(4):bbaa227. doi: 10.1093/bib/bbaa227.

  PMID: 33126247 BACKGROUND

• Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, Zeng Y, Miao R, Jin G, Ma H, Chen Y, Shen H. Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest. 2008 Jul;118(7):2600-8. doi: 10.1172/JCI34934.

  PMID: 18521189 BACKGROUND

• Gong WJ, Yin JY, Li XP, Fang C, Xiao D, Zhang W, Zhou HH, Li X, Liu ZQ. Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response. Tumour Biol. 2016 Jun;37(6):8349-58. doi: 10.1007/s13277-015-4497-5. Epub 2016 Jan 5.

  PMID: 26729200 BACKGROUND

• Hu P, Qiao O, Wang J, Li J, Jin H, Li Z, Jin Y. rs1859168 A > C polymorphism regulates HOTTIP expression and reduces risk of pancreatic cancer in a Chinese population. World J Surg Oncol. 2017 Aug 17;15(1):155. doi: 10.1186/s12957-017-1218-0.

  PMID: 28818070 BACKGROUND

• Wang BG, Xu Q, Lv Z, Fang XX, Ding HX, Wen J, Yuan Y. Association of twelve polymorphisms in three onco-lncRNA genes with hepatocellular cancer risk and prognosis: A case-control study. World J Gastroenterol. 2018 Jun 21;24(23):2482-2490. doi: 10.3748/wjg.v24.i23.2482.

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• Quagliata L, Matter MS, Piscuoglio S, Arabi L, Ruiz C, Procino A, Kovac M, Moretti F, Makowska Z, Boldanova T, Andersen JB, Hammerle M, Tornillo L, Heim MH, Diederichs S, Cillo C, Terracciano LM. Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. Hepatology. 2014 Mar;59(3):911-23. doi: 10.1002/hep.26740. Epub 2014 Jan 28.

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• Lewontin RC. On measures of gametic disequilibrium. Genetics. 1988 Nov;120(3):849-52. doi: 10.1093/genetics/120.3.849.

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Biospecimen

Retention: SAMPLES WITH DNA

Genomic DNA extracted from whole EDTA blood samples from all subjects according to the manufacturer's instructions. The aliquoted DNA is stored at -20°C refrigerator together with whole blood. While centrifuged separated sera are aliquoted and stored at -80°C refrigerator.

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Nadia Hamdy, PhD

  Faculty of Pharmacy, Ain Shams University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Biochemistry and Molecular Biology at Biochemistry department, Faculty of Pharmacy

Study Record Dates

• First Submitted: August 1, 2024
• First Posted: August 9, 2024
• Study Start: March 16, 2022
• Primary Completion: July 22, 2024
• Study Completion: December 31, 2024
• Last Updated: April 24, 2025

Record last verified: 2024-08

Locations

EG (1)