Role of LncRNA H19 in The Regulation of IGF-1R Expression

April 5, 2022 updated by: Mansoura University

Role of LncRNA H19 in The Regulation of IGF-1R Expression: A Possible Association Between Type 2 Diabetes and Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a common cancer that poses a heavy economic burden on the healthcare system. In Egypt, it is the most common cause of mortality and morbidity-related cancer. Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia. Cancer and type II diabetes (T2DM), the world's two most prevalent diseases, share many overlapping risk factors and predisposing pathological conditions. The exact mechanisms linking those two diseases are yet to be fully understood.

In this study, the investigators aim to assess the relationship between Long Non-Coding RNA (lncRNA) H19 and Insulin-Like Growth Factor 1 Receptor (IGF-1R) mRNA gene expressions in the blood samples of HCC & T2DM patients to investigate the probability of the presence of a pathophysiological link between HCC and DM that may become a therapeutic target for both diseases. To the investigator's knowledge, there is currently no human research study investigating both H19 and IGF-1R in both DM and cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hepatocellular carcinoma (HCC) is a common cancer that poses a heavy economic burden on the healthcare system. It represents the fourth and sixth most common cancer in Egypt and worldwide respectively. Globally, HCC is the fourth most common cause of death from cancer. It was estimated to be responsible for nearly 9.1% of the total deaths in 2012 (746,000 deaths). In Egypt, it is the most common cause of cancer-related mortality, and morbidity (32.35% of the total cancer deaths, mortality data were derived from the World Health Organization (WHO)). The leading risk factor in developing HCC in Egypt is hepatitis C virus (HCV).

Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, which may be caused by insufficient insulin secretion, insulin resistance, or augmented glucagon production. Cancer and type II diabetes (T2DM), The world's two most prevalent diseases, share many overlapping risk factors and predisposing pathological conditions. Although the T2DM-cancer co-existence has been noted for many decades, the exact mechanisms linking these diseases are yet to be fully understood.

Insulin-Like Growth Factor-1 Receptor (IGF-1R) is a member of the insulin and IGF family. It coordinates a complex downstream signaling network through which it plays essential roles in the regulation of cell growth, proliferation, and survival as well as in glucose homeostasis. IGF-1R plays a crucial role in many tumor-related courses, such as tumor growth and metastasis in addition to drug resistance. The IGF-1R dysregulated signaling pathways in cancer and DM have been reported to be controlled at different levels by non-coding RNAs.

Non-coding RNAs (ncRNAs) are a large category of RNAs that usually do not participate in protein encoding but have a wide range of biological functions through regulation of protein expression and functions. The two most researched classes of ncRNAs are microRNAs (miRNAs) and the long non-coding RNAs (lncRNAs). H19 is a lncRNA that is found to be overexpressed in many solid tumors including HCC. The relationship between H19 and IGF-1R expression levels in addition to the dysregulation of H19 in DM are still inconsistent in literature, warranting further investigations. Ghazal et al. noted that H19 levels are directly proportional to IGF-1R expression levels in women with endometriosis (Ghazal et al., 2015). This is conflicting with Farzi-Molan et al. who remarked the reverse relation between IGF-1R & H19 during the differentiation of Bone Marrow Mesenchymal Stem Cells (BMSCs) to neural cells

Study Type

Observational

Enrollment (Actual)

101

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
    • Dakahliya
      • Mansoura, Dakahliya, Egypt, 35516
        • Gastroenterology Center, Mansoura University
      • Mansoura, Dakahliya, Egypt, 35516
        • Specialized Medical Hospital, Mansoura University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

This case-control study will be conducted in the Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University. Blood samples will be obtained from 24 HCC patients and 24 HCC & T2DM patients at the Gastroenterology Center, Mansoura University as well as from 26 T2DM patients at the Specialized Medical Hospital, Mansoura University in the period from December 2020 to December 2021.

The study will include 101 patients divided into 4 groups:

Group I: 24 HCC patients Group II: 26 T2DM patients Group III: 24 HCC & T2DM patients Group IV: 27 age and gender-matched healthy control volunteers. Written informed consent will be obtained from all individuals.

Description

• HCC cases (group I):

Inclusion criteria:

- Patients aged 40 years or older with a confirmed diagnosis of HCC through triphasic CT and/or dynamic MRI (European Association for the Study of the Liver, 2012).

Exclusion criteria:

  • Patients who underwent previous cancer-directed treatment (radiation and/or chemotherapy).

  • Patients with any other systemic disease (Renal disease, other primary tumors).

    • T2DM cases (group II):

Inclusion criteria:

- Clinically diagnosed T2DM patients aged 40 years or older frequenting Mansoura Specialized Medical Hospital.

Exclusion criteria:

  • Patients with previous or current malignancies.
  • Patients with diabetic complications (Diabetic retinopathy, neuropathy, nephropathy).

  • Patients with other systemic diseases.

    • HCC & T2DM cases (group III):

Inclusion criteria:

- Patients aged 40 years or older with a confirmed diagnosis of HCC through triphasic CT and/or dynamic MRI and who are clinically diagnosed to have T2DM.

Exclusion criteria:

  • Patients who underwent previous cancer-directed treatment (radiation and/or chemotherapy).

  • Patients with any other systemic disease.

    • Controls (group IV):

  • Apparently healthy, age, and gender-matched subjects.
  • No history of malignant disease, diabetes, or HCV.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
HCC patients
Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples.
Other: Blood sample collection

5ml of peripheral blood samples will be collected into tubes containing EDTA from all subjects and the following procedures will be performed:

  • Peripheral blood mononuclear cells (PBMCs) will be isolated from blood samples.
  • Total RNA extraction from PBMCs by Trizol reagent and spin column.
  • Reverse transcription to cDNA.
  • The expression levels of lncRNA H19, IGF-1R mRNA and GAPDH gene (control gene) will be determined by Real-Time Quantitative PCR
T2DM patients
Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples.
Other: Blood sample collection

5ml of peripheral blood samples will be collected into tubes containing EDTA from all subjects and the following procedures will be performed:

  • Peripheral blood mononuclear cells (PBMCs) will be isolated from blood samples.
  • Total RNA extraction from PBMCs by Trizol reagent and spin column.
  • Reverse transcription to cDNA.
  • The expression levels of lncRNA H19, IGF-1R mRNA and GAPDH gene (control gene) will be determined by Real-Time Quantitative PCR
HCC & T2DM patients
Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples.
Other: Blood sample collection

5ml of peripheral blood samples will be collected into tubes containing EDTA from all subjects and the following procedures will be performed:

  • Peripheral blood mononuclear cells (PBMCs) will be isolated from blood samples.
  • Total RNA extraction from PBMCs by Trizol reagent and spin column.
  • Reverse transcription to cDNA.
  • The expression levels of lncRNA H19, IGF-1R mRNA and GAPDH gene (control gene) will be determined by Real-Time Quantitative PCR
Controls
Measure lncRNA H19 and IGF-1R mRNA gene expression levels in the collected blood samples.
Other: Blood sample collection

5ml of peripheral blood samples will be collected into tubes containing EDTA from all subjects and the following procedures will be performed:

  • Peripheral blood mononuclear cells (PBMCs) will be isolated from blood samples.
  • Total RNA extraction from PBMCs by Trizol reagent and spin column.
  • Reverse transcription to cDNA.
  • The expression levels of lncRNA H19, IGF-1R mRNA and GAPDH gene (control gene) will be determined by Real-Time Quantitative PCR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Measurement of the gene expression levels of LncRNA H19 & IGF-1R mRNA, normalized to the housekeeping gene GAPDH expression level, in HCC and T2DM in comparison with healthy controls using Real-Time Quantitative PCR (by the 2^-ΔΔCT method).
Time Frame: baseline

To assess if there is a correlation between lncRNA H19 and IGF-1R mRNA gene expressions in the blood samples of HCC & T2DM patients to investigate the probability of the presence of a pathophysiological link between HCC and DM:

  • To measure the IGF-1R mRNA and lncRNA H19 expression levels in HCC & T2DM patients in comparison with healthy controls.
  • To investigate whether lncRNA H19 and IGF-1R mRNA expression levels affect one another.
  • To compare IGF-1R and lncRNA H19 expression levels in HCC associated with T2DM patients in contrast with sole affection with HCC or T2DM.
baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mansoura University

Investigators

  • Principal Investigator: Noura MS Shehabeldin, M.B.B.Ch, Faculty of Medicine, Mansoura University.
  • Study Director: Mohamed AA Zahran, M.D., Faculty of Medicine, Mansoura University.
  • Study Chair: Heba K Mohamed, M.D., Faculty of Medicine, Mansoura University.
  • Study Chair: Nora M Hussein, M.D., Faculty of Medicine, Mansoura University.
  • Study Chair: Ahmed Shehta, M.D., Gastroenterology Center, Mansoura University
  • Study Chair: Helmy Ezzat, M.D., Gastroenterology Center, Mansoura University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2020

Primary Completion (Actual)

January 30, 2022

Study Completion (Actual)

April 4, 2022

Study Registration Dates

First Submitted

December 21, 2020

First Submitted That Met QC Criteria

February 22, 2021

First Posted (Actual)

February 23, 2021

Study Record Updates

Last Update Posted (Actual)

April 7, 2022

Last Update Submitted That Met QC Criteria

April 5, 2022

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MS.20.10.26

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cancer

Clinical Trials on Blood sample collection

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Israel

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe