Assessment of Glypican 3 as Apredictive Marker in Colorectal Cancer Patients

Assessment of Glypican 3 as a Predictive Marker in Colorectal Cancer Patients

• Evaluation Of Glypican 3 in serum of colorectal cancer patients .
• Correlation between Glypican 3 and clinicopathological characteristics of colorectal cancer .

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Diagnostic test: glypican 3

Detailed Description

Colorectal cancer (CRC) is the third most common malignancy and the fourth most prominent cause of cancer-related deaths worldwide. Also it is the 7th commonest cancer in Egypt, representing 3.47% of male cancers and 3% of female cancers.The Glypicans , a family of proteins classified as HSPGs (heparan sulfate proteoglycan) , have been shown to interact with a number of growth factors and modulate growth factor activity and are linked to the xtracellular side of cell membrane by a glycosylphosphatidylinositol (GPI) anchor . Members of this large family of transmembrane proteins have been identified in both mammals and drosophila: 6 glypicans (GPC-1 through GPC-6) in mammals, and two others in the fly .Glypican-3 (GPC3) as one of this family is a protein of about 70 kD . It has multiple sugar chains and heparan sulfate modification sites . These proteins (Glypicans) participate in organ development by modulating extracellular growth signals and morphogen gradient formation, and are involved in human overgrowth and skeletal dysplasia problems .In some cancers, they are highly expressed, associated with tumorigenesis, and regulating angiogenesis for cancer progression and invasion . Abnormal expression of glypicans has been noted in multiple types of cancer. For examples, GPC-1 expression was found to be increased in breast cancer tissues and ovarian malignant tumors .GPC-2 is associated with neuroblastoma .Expression of GPC-3 was found in high-grade urothelial carcinoma and also reported in some non-CNS tumors of the brain.There have been several reports about the clinical usefulness of the N-terminal form of GPC3. Enzyme-linked immunosorbent assay methods capable of detecting the N-terminal form of GPC3 . A study of colorectal cancer tissue speciment shows a correlation between expression of GPC3 with the clinicopathologic variables such as the level of differentiation, GPC3 was found to be expressed in ( 42.8% ) of the well-differentiated tumors, and (50%) of the moderately differentiated tumors, (75%) of the moderately and poorly differentiated tumors .Therefore, it was found that the expression of GPC3 was correlated with the pathological grade of the tumors .

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Reham Hany Mohammed; Phone Number: 01118441744; Email: rehamhany809@gmail.com
• Study Contact Backup: Name: Hosney Badrawy Hamed; Phone Number: 01060664976; Email: BadranH@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with colorectal cancer and admitted to south egypt cancer institute .

Exclusion Criteria:

• Other malignant diseases .
• Patients received chemotherapy for colorectal cancer .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: patients with colorecta cancer	Diagnostic test: glypican 3; Assessment of glypican 3 presence in colorectal cancer patients using ELISA
No Intervention: healthy individuals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Glypican 3 role as a predictive and diagnostic marker of colorectal marker .	measurment of GLYPICAN 3 level in serum of colorectal patients using ELISA method	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Addition of Glypican 3 to the routine markers of colorectal cancer . - Correlatin of this marker with the disease pathology and management procedures .	measurment of GLYPICAN 3 level in serum of colorectal patients using ELISA method	3 years

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• Terzic J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010 Jun;138(6):2101-2114.e5. doi: 10.1053/j.gastro.2010.01.058.
• Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H. Cancer incidence in egypt: results of the national population-based cancer registry program. J Cancer Epidemiol. 2014;2014:437971. doi: 10.1155/2014/437971. Epub 2014 Sep 21.
• Ijaz B, Formentin E, Ronci B, Locato V, Barizza E, Hyder MZ, Lo Schiavo F, Yasmin T. Salt tolerance in indica rice cell cultures depends on a fine tuning of ROS signalling and homeostasis. PLoS One. 2019 Apr 30;14(4):e0213986. doi: 10.1371/journal.pone.0213986. eCollection 2019.
• Filmus J, Selleck SB. Glypicans: proteoglycans with a surprise. J Clin Invest. 2001 Aug;108(4):497-501. doi: 10.1172/JCI13712. No abstract available.
• Shirakawa H, Kuronuma T, Nishimura Y, Hasebe T, Nakano M, Gotohda N, Takahashi S, Nakagohri T, Konishi M, Kobayashi N, Kinoshita T, Nakatsura T. Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer. Int J Oncol. 2009 Mar;34(3):649-56. doi: 10.3892/ijo_00000190.
• Sarrazin S, Lamanna WC, Esko JD. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol. 2011 Jul 1;3(7):a004952. doi: 10.1101/cshperspect.a004952.
• Fico A, Maina F, Dono R. Fine-tuning of cell signaling by glypicans. Cell Mol Life Sci. 2011 Mar;68(6):923-9. doi: 10.1007/s00018-007-7471-6. Epub 2011 Feb 22.
• Matsuda K, Maruyama H, Guo F, Kleeff J, Itakura J, Matsumoto Y, Lander AD, Korc M. Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells. Cancer Res. 2001 Jul 15;61(14):5562-9.
• Davies EJ, Blackhall FH, Shanks JH, David G, McGown AT, Swindell R, Slade RJ, Martin-Hirsch P, Gallagher JT, Jayson GC. Distribution and clinical significance of heparan sulfate proteoglycans in ovarian cancer. Clin Cancer Res. 2004 Aug 1;10(15):5178-86. doi: 10.1158/1078-0432.CCR-03-0103.
• Bosse KR, Raman P, Zhu Z, Lane M, Martinez D, Heitzeneder S, Rathi KS, Kendsersky NM, Randall M, Donovan L, Morrissy S, Sussman RT, Zhelev DV, Feng Y, Wang Y, Hwang J, Lopez G, Harenza JL, Wei JS, Pawel B, Bhatti T, Santi M, Ganguly A, Khan J, Marra MA, Taylor MD, Dimitrov DS, Mackall CL, Maris JM. Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma. Cancer Cell. 2017 Sep 11;32(3):295-309.e12. doi: 10.1016/j.ccell.2017.08.003.
• Aleksikova RIa. [On the morbidity of school-children in senior classes of Leningrad boarding schools]. Zdravookhr Ross Fed. 1965 Nov;9(11):11-3. No abstract available. Russian.
• Chan ES, Pawel BR, Corao DA, Venneti S, Russo P, Santi M, Sullivan LM. Immunohistochemical expression of glypican-3 in pediatric tumors: an analysis of 414 cases. Pediatr Dev Pathol. 2013 Jul-Aug;16(4):272-7. doi: 10.2350/12-06-1216-OA.1. Epub 2013 Mar 26.
• Haruyama Y, Yorita K, Yamaguchi T, Kitajima S, Amano J, Ohtomo T, Ohno A, Kondo K, Kataoka H. High preoperative levels of serum glypican-3 containing N-terminal subunit are associated with poor prognosis in patients with hepatocellular carcinoma after partial hepatectomy. Int J Cancer. 2015 Oct 1;137(7):1643-51. doi: 10.1002/ijc.29518. Epub 2015 Apr 6.

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: September 13, 2020
• First Submitted That Met QC Criteria: January 23, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): January 13, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: glypican 3
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: Colorectal Cancer

Plan for Individual participant data (IPD)

Study Data/Documents

1. Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No