The Value of circRNAs (hsa_circ_0004001) in Early Diagnosis of HCC

October 1, 2023 updated by: Marwa Aboelim Shafeik, Assiut University
  1. To evaluate the clinical utility of plasma circRNAs (hsa_circ_0004001) as a non invasive diagnostic biomarker for HCC patients and to differentiate between malignant and nonmalignant hepatic disorders.
  2. To study the relation of circRNAs (hsa_circ_0004001) to HCC staging.
  3. To compare between circRNAs (hsa_circ_0004001) and the routine marker (AFP) as biomarkers for HCC diagnosis.

Study Overview

Status

Not yet recruiting

Conditions

Detailed Description

Hepatocellular carcinoma (HCC) is one of the most common malignant gastrointestinal tumours worldwide and is characterized by high morbidity and mortality rates . HCC is the sixth common cancer and the second leading cause of death from cancer worldwide.

The American Cancer Society's estimates for deaths by primary liver cancer and intrahepatic bile duct cancer in the United States for 2018 are 30200. HCC incidence in Egypt has increased sharply over the last decade due to the high prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among Egyptians. Indeed, liver cancer is the most frequent cancer in both men and women in Egypt. HCC was the first among the most frequently observed cancers in lower and middle Egypt and the 2nd in upper Egypt, of patients with liver cirrhosis, 3%-5% develop HCC annually. In Egypt, HCC represents nearly 70% of all liver tumors.

Unfortunately, upon diagnosis, most of the patients are in the advanced stages of the disease. Thus, early diagnosis is a key in improving the HCC treatment and prognosis. Liver cancer screening is typically based on the detection of serum alpha-fetoprotein and various imaging methods. Moreover, imaging techniques are costly, and the patients' compliance is poor. The diagnostic and treatment strategies that are available for HCC, it still cannot be detected at early stages efficiently. The diagnostic methods fail to detect HCC in many patients. Consequently, curative treatments may no longer be efficient at the time of diagnosis because of intra- and extrahepatic metastases. The combination of serum alpha-fetoprotein (AFP) and ultrasound surveillance is the most widely used method for screening and detection of HCC in high-risk groups. However, ultrasound surveillance is limited by the sensitivity of the detection and often results in misdiagnosis of small malignant nodules, especially in cirrhosis. Therefore, due to their poor sensitivity and specificity, there is a great need to improve the current HCC diagnostic methods. The search for novel potential biomarkers is crucial to increase the rate of early detection.

Circular RNAs (circRNAs) are a type of single-stranded RNA which, unlike linear RNA, forms a covalently closed continuous loop. In circular RNA, the 3' and 5' ends normally present in an RNA molecule have been joined together. Because circular RNA does not have 5' or 3' ends, it is resistant to exonuclease-mediated degradation and is presumably more stable than most linear RNA in cells. They are covalently closed loops generated by the back splicing of precursor mRNA (premRNA) molecules, which exist widely in mammalian cells and are characterized by stability, conservative evolution, and cell or tissue specificity. These characteristics endow circRNAs with many biological functions, such as acting as microRNA (miRNA) sponges, regulating the transcription of parental genes, binding RNA binding proteins (RBPs), and encoding proteins and peptides. The circRNA is a type of non-coding RNA and type of nucleic acid molecule found in exosomes, forms a covalently bonded closed loop without 5' caps or 3' poly(A) tails. Most circRNAs have the following characteristics: (1) High abundance: The abundance of circRNA expression varies greatly; in some cases, the abundance of circRNAs exceeds 10 times that of their linear RNA counterparts; (2) Stability: The stability of circRNAs is 2.5-5 times higher than that of linear transcripts because the unique covalently closed loop of circRNAs lacks 3' and 5' ends, resulting in the absence of ribonuclease binding targets; therefore, circRNAs are not easily degraded; (3) Conservation: CircRNAs are widely present in different species and are evolutionarily conserved. Some studies suggest that most circRNAs in different species are evolutionarily conserved, while a few are not conserved ; and (4) Specificity: CircRNAs have tissue and cell specificity, with differential expression in different stages of ontogeny and disease progression .

They are superior to other non-coding RNAs as molecular diagnostic markers and drug treatment targets. Exosomal-derived circRNAs in the body fluids of tumours patients can modulate tumour proliferation, invasion, metastasis, and drug resistance. They can be used as effective biomarkers for early non-invasive diagnosis and prognostic evaluation of tumours and represent ideal targets for early precision therapeutic intervention. The circRNA secreted into human circulating blood can be used as a biomarker for disease diagnosis . Our knowledge of the pathogenesis of hepatocellular carcinoma (HCC) is incomplete. The effective treatment methods are surgery or transplantation, but the recurrence and metastasis rates are still high with a low 5-year survival rate . Many circRNAs are involved in the proliferation, apoptosis, migration, and invasion of HCC cells. Therefore, circRNA may be an important biomarker for the clinical diagnosis and treatment of HCC. According to the effect on the malignant phenotype of HCC cells, circRNAs can be divided into carcinogenic circRNAs and tumor suppressor circRNAs. Compared with the adjacent tissues and normal liver cell lines, the expression of cancer-promoting circRNAs in HCC tissues and HCC cell lines is usually high. Inhibiting the expression of carcinogenic circRNAs can significantly reduce the proliferation, migration, and invasion of HCC cells, promote the apoptosis of HCC cells, and improve the prognosis Recent studies demonstrated that numerous circRNAs were differentially expressed in HCC tissues, which is closely related with the development and prognosis of HCC, and indicated that circRNA plays vital roles in tumorigenesis and progression of HCC and could be used as a diagnostic biomarker

Study Type

Observational

Enrollment (Estimated)

102

Contacts and Locations

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

Study Contact

Study Contact Backup

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Non-Probability Sample

Study Population

(102 )individuals aged (18 years to 80years), did not receive any chemotherapy or surgical treatment The study will be carried out on patients who will be admitted to gastroenterology department at Assiut University hospital, and will be conducted at clinical pathology department, Assiut University Hospital, Faculty of medicine, Assiut University

Description

Inclusion Criteria:

  1. group one patients early diagnosed as HCC
  2. group two patient diagnosed with chronic non-malignant liver disease 3 group three healthy control group

Exclusion Criteria:

  1. Patients with any other type of malignant or benign tumors should be excluded from our study.
  2. History of chemotherapy or surgical treatment of cancer

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
group 1
healthy control
group 2
patient with hepatic cell carcinoma
group 3
patient with non malignant liver diseased

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
(1) To evaluate the clinical utility of plasma circRNAs (hsa_circ_0004001)by Q-PCR as a non invasive diagnostic biomarker for HCC patients and to differentiate between malignant and nonmalignant hepatic disorders
Time Frame: baseline
  1. To evaluate the clinical utility of plasma circRNAs (hsa_circ_0004001) by Q-PCR as a non invasive diagnostic biomarker for HCC patients and to differentiate between malignant and nonmalignant hepatic disorders
  2. To study the relation of circRNAs (hsa_circ_0004001) to HCC staging.
  3. To compare between circRNAs (hsa_circ_0004001) and the routine marker (AFP) as biomarkers for HCC diagnosis
baseline

Collaborators and Investigators

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

Sponsor

Assiut 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.

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 (Estimated)

November 1, 2023

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

February 1, 2025

Study Registration Dates

First Submitted

September 12, 2023

First Submitted That Met QC Criteria

September 12, 2023

First Posted (Actual)

September 21, 2023

Study Record Updates

Last Update Posted (Actual)

October 4, 2023

Last Update Submitted That Met QC Criteria

October 1, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CircRNA in HCC

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.

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