Association of Autophagy-related Genes ,LncRNA and SNPs With Colorectal Cancer in Egyptian Population

Completed

• Conditions: Colo-rectal Cancer
• Interventions: Diagnostic Test: PBMCs and Tissue expression of HOTTIP ,EIF4EBP1 and serum SNP HOTTIP rs1859168

• Registration Number: NCT04729855
• Lead Sponsor: Esraa Hassan,MD

Brief Summary

1. Determination of expression level of HOTTIP and EIF4EBP1(Eukaryotic translation initiation factor 4E-binding protein 1) .

2. Investigation of the SNP HOTTIP rs1859168 and it's association with CRC susceptibility.

3. Correlation of the expression of these genes with various stages of CRC to determine the prognostic value of each of them.

Detailed Description

Colorectal cancer (CRC) is a common digestive tract tumor 1.It is the third leading cause of death in the world. Overall 5-year survival rate is less than 40%, and the occurrence is rising 2. However, the prognosis and therapy have not been significantly improved. Therefore, a proper selection of patients for aggressive treatment is necessary, new therapeutic and prognostic strategies are urgently needed 3.

Autophagy is a pathway for self-digestion, in which unwanted cytoplasmic components are recycled 4.In normal conditions, autophagy is essential for cellular homeostasis 5. Autophagy has dual roles in cancer cells, stimulation or suppression , with effects on progression and oncogenesis 6.Recent research established that autophagy is important target for controlling cancer depending on stage and type of tumor 7.Diverse molecular mechanisms contribute to cancer cells resistance to treatment 8.Among these mechanisms , autophagy appears to be critical 9.

EIF4EBP1 (Eukaryotic translation initiation factor 4E-binding protein 1) is encoded by EIF4EBP1 gene.It acts as an effector in mTOR (mammilian target of rapamycin) pathway which on activation ,EIF4EBP1 is phosphorylated promoting cell proliferation 10. Studies have suggested that EIF4EBP1 promotes carcinogenesis as in hepatocellular carcinoma .However, its role in CRC have not been elucidated 10.

Long non-coding RNAs (lncRNAs) are group of RNA , 200 nucleotides in length 11,. Expression of lncRNAs has been discovered in multiple tumors, acting as oncogenes. 'HOXA(hydrogenase transcriptional regulatory protein) transcript at the distal tip' (HOTTIP) has received attention lately.It is up-regulated in CRC tissue, regulating genes via epigenetic modification. Therefore, it might be a candidate for cancerization and therapy of CRC 12.

Expression of lncRNAs could be affected by single nucleotide polymorphisms (SNPs), the most common genetic variation in human genomes13. rs1859168 was reported as a potential functional polymorphism on HOTTIP that alters its expression level 14.. Also, it was recently reported that HOTTIP enhances interleukin 6 expression, which potentiates immune escape of cancer cells 15.

Study Timeline

• Study First Submitted: 2021-01-24
• Study First Submitted QC: 2021-01-27
• Study First Posted: 2021-01-29
• Study Start: 2022-04-15
• Primary Completion: 2023-05-20
• Study Completion: 2024-09-20
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-27
• Last Update Posted: 2025-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• No sex predilection.
• Age (25-65 yr).
• Colorectal carcinoma confirmed by histopathological examination

Exclusion Criteria

• -patients who received any treatment.
• Cases with other organ cancers.
• History of chemotherapy and radiotherapy.
• Systemic diseases such as renal failure, diabetes mellitus, and hypertension.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Healthy controls ( n = 30)	PBMCs and Tissue expression of HOTTIP ,EIF4EBP1 and serum SNP HOTTIP rs1859168	matched as regarding age and sex as much as possible with cases.
colorectal cancer patients	PBMCs and Tissue expression of HOTTIP ,EIF4EBP1 and serum SNP HOTTIP rs1859168	Colorectal cancer patients( n = 30 ) from stage I-III with the following criteria:- a. Inclusion criteria: * No sex predilection. * Age (25-65 yr). * Colorectal carcinoma confirmed by histopathological examination

Primary Outcome Measures

Name	Time	Method
HOTTIP gene expression	2 years	Estimation of expression level of HOTTIP in peripheral blood mononuclear cells and tissue aiming to use as possible less invasive prognostic markers for colorectal cancer.

Secondary Outcome Measures

Name	Time	Method
EIF4EBP	2 years	Estimation of expression level of EIF4EBP in peripheral blood mononuclear cells and tissue

Trial Locations

Locations (1)

Assiut University; 🇪🇬 Assiut, Egypt