Association of Two CD44 Polymorphisms with Clinical Outcomes of Gastric Cancer Patients

Overview

Journal Asian Pac J Cancer Prev

Specialty Oncology

Date 2018 May 27

PMID 29802692

Citations 4

Authors

Seyed Mohammadreza Bitaraf

Reihaneh Alsadat Mahmoudian

Mohammadreza Abbaszadegan

Anahita Mohseni Meybodi

Negin Taghehchian

Atena Mansouri

Mohammad Mahdi Forghanifard

Bahram Memar

Mehran Gholamin

Affiliations

Soon will be listed here.

Abstract

Objective: CD44 is an important cell adhesion molecule that plays a key role in growth, invasion, proliferation and metastasis of cancer cells. CD44 protein over-expression is associated with a poor prognosis of gastric cancer (GC) and previous studies have shown that CD44 gene polymorphisms could affect survival and recurrence. In this study, we tested the hypothesis that polymorphisms impacting on the CD44 signaling pathway may predict clinical outcomes in patients with GC. Materials and Methods: DNA was extracted from blood of 150 healthy individuals and formalin-fixed paraffin-embedded (FFPE) tumor tissue of 150 patients. The two polymorphisms rs187116 and rs7116432 were studied by RFLP-PCR and sequencing techniques. Results: There was a strong significant correlation between single nucleotide polymorphisms (SNPs) in the CD44 gene, tumor recurrence, and overall survival (p <0.0001). The existence of a significant relationship between tumor recurrence and overall survival was proved in this study, with at least one allele G for the polymorphism rs187116 and at least one allele A for polymorphism rs7116432. Conclusion: These results provide evidence of a relationship between CD44 gene polymorphisms and clinical outcomes in our GC patients. This result could help identify individuals with GC who have a high risk of tumor recurrence.

Citing Articles

Common Variants in Osteopontin and Genes as Predictors of Treatment Outcome in Radiotherapy and Chemoradiotherapy for Non-Small Cell Lung Cancer.

Galecki S, Gdowicz-Klosok A, Deja R, Maslyk B, Giglok M, Suwinski R Cells. 2023; 12(23).

PMID: 38067149 PMC: 10706014. DOI: 10.3390/cells12232721.

CD44 as a tumor biomarker and therapeutic target.

Xu H, Niu M, Yuan X, Wu K, Liu A Exp Hematol Oncol. 2020; 9(1):36.

PMID: 33303029 PMC: 7727191. DOI: 10.1186/s40164-020-00192-0.

The Role of Cancer Stem Cells in Radiation Resistance.

Arnold C, Mangesius J, Skvortsova I, Ganswindt U Front Oncol. 2020; 10:164.

PMID: 32154167 PMC: 7044409. DOI: 10.3389/fonc.2020.00164.

Gene Combination of CD44 rs187116, CD133 rs2240688, NF-κB1 rs28362491 and GSTM1 Deletion as a Potential Biomarker in Risk Prediction of Breast Cancer in Lower Northern Thailand.

Sapcharoen K, Sanguansermsri P, Yasothornsrikul S, Muisuk K, Srikummool M Asian Pac J Cancer Prev. 2019; 20(8):2493-2502.

PMID: 31450925 PMC: 6852831. DOI: 10.31557/APJCP.2019.20.8.2493.

References

Pagani F, Baralle F . Genomic variants in exons and introns: identifying the splicing spoilers. Nat Rev Genet. 2004; 5(5):389-96. DOI: 10.1038/nrg1327. View

Malekzadeh R, Derakhshan M, Malekzadeh Z . Gastric cancer in Iran: epidemiology and risk factors. Arch Iran Med. 2009; 12(6):576-83. View

Bourguignon L, Zhu H, Chu A, Iida N, Zhang L, Hung M . Interaction between the adhesion receptor, CD44, and the oncogene product, p185HER2, promotes human ovarian tumor cell activation. J Biol Chem. 1997; 272(44):27913-8. DOI: 10.1074/jbc.272.44.27913. View

Lin Y . The osteopontin-CD44 survival signal involves activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. J Biol Chem. 2001; 276(49):46024-30. DOI: 10.1074/jbc.M105132200. View

Narla G, DiFeo A, Reeves H, Schaid D, Hirshfeld J, Hod E . A germline DNA polymorphism enhances alternative splicing of the KLF6 tumor suppressor gene and is associated with increased prostate cancer risk. Cancer Res. 2005; 65(4):1213-22. DOI: 10.1158/0008-5472.CAN-04-4249. View

Tijink B, Buter J, de Bree R, Giaccone G, Lang M, Staab A . A phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res. 2006; 12(20 Pt 1):6064-72. DOI: 10.1158/1078-0432.CCR-06-0910. View

LAUREN P . THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. Acta Pathol Microbiol Scand. 1965; 64:31-49. DOI: 10.1111/apm.1965.64.1.31. View

Ghaffarzadehgan K, Jafarzadeh M, Raziee H, Sima H, Esmaili-Shandiz E, Hosseinnezhad H . Expression of cell adhesion molecule CD44 in gastric adenocarcinoma and its prognostic importance. World J Gastroenterol. 2008; 14(41):6376-81. PMC: 2766121. DOI: 10.3748/wjg.14.6376. View

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

10.

Qiu Y, Hu Y, Zhang Z, Ye L, Xu F, Schneider M . Genetic association of osteopontin (OPN) and its receptor CD44 genes with susceptibility to Chinese gastric cancer patients. J Cancer Res Clin Oncol. 2014; 140(12):2143-56. DOI: 10.1007/s00432-014-1761-9. View

11.

Klingbeil P, Marhaba R, Jung T, Kirmse R, Ludwig T, Zoller M . CD44 variant isoforms promote metastasis formation by a tumor cell-matrix cross-talk that supports adhesion and apoptosis resistance. Mol Cancer Res. 2009; 7(2):168-79. DOI: 10.1158/1541-7786.MCR-08-0207. View

12.

Huh J, Kim H, Kim Y, Lee J, Park Y, Cho S . Expression of standard CD44 in human colorectal carcinoma: association with prognosis. Pathol Int. 2009; 59(4):241-6. DOI: 10.1111/j.1440-1827.2009.02357.x. View

13.

Rupp U, Schoendorf-Holland E, Eichbaum M, Schuetz F, Lauschner I, Schmidt P . Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: final results of a phase I study. Anticancer Drugs. 2007; 18(4):477-85. DOI: 10.1097/CAD.0b013e32801403f4. View

14.

Takaishi S, Okumura T, Tu S, Wang S, Shibata W, Vigneshwaran R . Identification of gastric cancer stem cells using the cell surface marker CD44. Stem Cells. 2009; 27(5):1006-20. PMC: 2746367. DOI: 10.1002/stem.30. View

15.

Gunthert U, Hofmann M, Rudy W, Reber S, Zoller M, Haussmann I . A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991; 65(1):13-24. DOI: 10.1016/0092-8674(91)90403-l. View

16.

DAngelica M, Gonen M, Brennan M, Turnbull A, Bains M, Karpeh M . Patterns of initial recurrence in completely resected gastric adenocarcinoma. Ann Surg. 2004; 240(5):808-16. PMC: 1356486. DOI: 10.1097/01.sla.0000143245.28656.15. View

17.

Barbour A, Reeder J, Walsh M, Fawcett J, Antalis T, Gotley D . Expression of the CD44v2-10 isoform confers a metastatic phenotype: importance of the heparan sulfate attachment site CD44v3. Cancer Res. 2003; 63(4):887-92. View

18.

Lesley J, English N, Gal I, Mikecz K, Day A, Hyman R . Hyaluronan binding properties of a CD44 chimera containing the link module of TSG-6. J Biol Chem. 2002; 277(29):26600-8. DOI: 10.1074/jbc.M201068200. View

19.

Shukla S, Duan S, Wu X, Badner J, Kasza K, Dolan M . Whole-genome approach implicates CD44 in cellular resistance to carboplatin. Hum Genomics. 2009; 3(2):128-42. PMC: 2683878. DOI: 10.1186/1479-7364-3-2-128. View

20.

Wielenga V, Heider K, Offerhaus G, Adolf G, van den Berg F, Ponta H . Expression of CD44 variant proteins in human colorectal cancer is related to tumor progression. Cancer Res. 1993; 53(20):4754-6. View