Ignite Creation Date:
2024-05-06 @ 7:32 PM
Last Modification Date:
2024-10-26 @ 3:08 PM
Study NCT ID:
NCT06042842
Status:
NOT_YET_RECRUITING
Last Update Posted:
2023-10-04
First Post:
2023-09-12
Brief Title:
The Value of circRNAs hsa_circ_0004001 in Early Diagnosis of HCC
Sponsor:
Assiut University
Organization:
Assiut University
Study Overview
Official Title:
The Value of circRNAs hsa_circ_0004001 in Early Diagnosis of HCC
Status:
NOT_YET_RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
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 Societys 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 polyA 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 25-5 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
The American Cancer Societys 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 polyA 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 25-5 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None