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

Study Overview
=================
Brief Summary
-----------------
Determination of serum expression level of HOTTIP and EIF4EBP1(Eukaryotic translation initiation factor 4E-binding protein 1) . Investigation of the SNP HOTTIP rs1859168 and it's association with CRC susceptibility. Determination of serum level of Interleukin -6 and its relation to other studied genes. 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.

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

Conditions
-----------------
Colo-rectal Cancer

Intervention / Treatment
-----------------
* Diagnostic Test: serum HOTTIP ,EIF4EBP1 and serum SNP HOTTIP rs1859168


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| colorectal cancer patients<br>Colorectal cancer patients( n = 74 ) from stage I-III with the following criteria:- a. Inclusion criteria: No sex predilection. Age (25-65 yr). Colorectal carcinoma confirmed by histopathological examination | Diagnostic Test: serum HOTTIP ,EIF4EBP1 and serum SNP HOTTIP rs1859168<br>* 5 ml fresh blood sample<br>|
| Healthy controls ( n = 74)<br>matched as regarding age and sex as much as possible with cases. | Diagnostic Test: serum HOTTIP ,EIF4EBP1 and serum SNP HOTTIP rs1859168<br>* 5 ml fresh blood sample<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HOTTIP gene expression | Estimation of expression level of HOTTIP in peripheral blood mononuclear cells aiming to use as possible less invasive prognostic markers for colorectal cancer. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EIF4EBP | Estimation of expression level of EIF4EBP in peripheral blood mononuclear cells | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Colorectal cancer, HOTTIP