Defensin Alpha 6 (DEFA 6) Overexpression Threshold of over 60 Fold Can Distinguish Between Adenoma and Fully Blown Colon Carcinoma in Individual Patients

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2010 Oct 29

PMID 20979654

Citations 8

Authors

Mariya Y Radeva

Franziska Jahns

Anne Wilhelm

Michael Glei

Utz Settmacher

Karl Otto Greulich

Henning Mothes

Affiliations

Soon will be listed here.

Abstract

Background: It is known that alpha-defensin expression is enhanced in colon cancer. However, the expression of human alpha defensin 6 (DEFA 6) in earlier stages, such as adenoma, has so far not yet been studied in a patient resolved manner.

Methods: By using quantitative Real Time-PCR, the gene expression pattern of DEFA 1-3 and DEFA 6 was analyzed in tissue of different stages of carcinogenesis, derived from colorectal cancer patients. In addition to paired normal and tumor tissue, matched normal near tumor and adenoma tissue samples were examined.

Results: The median gene expression of human defensin alpha 6 (DEFA 6) has been found to be moderately increased (~ 5 fold) in tumor samples derived from individuals with colorectal cancer (CRC) when compared to their normal counterparts. However, when the data were analyzed in a patient-wise manner, a large expression variation among individual patients is found, making the use of DEFA 6 for individual diagnosis of fully blown colon carcinoma difficult. Surprisingly, in adenoma the gene expression analysis revealed a 100 fold increased median expression of DEFA 6 relative to normal colon tissue. 13/18 samples had an individual overexpression of more than 60 fold in adenoma but only 3/17 in carcinoma. In each of the individual patients, at least either the adenoma or the carcinoma showed strong DEFA 6 overexpression.

Conclusions: We suggest that the expression of DEFA 6 preferably can be used as a potential diagnostic marker for adenoma and not as a marker for fully blown carcinoma. This is supported by the fact that DEFA 6 is a downstream target of the Wnt pathway, which is mutational active during the earliest stage of cancer development.

Citing Articles

Comprehensive analysis of alfa defensin expression and prognosis in human colorectal cancer.

Zhao X, Lu M, Liu Z, Zhang M, Yuan H, Dan Z Front Oncol. 2023; 12:974654.

PMID: 36703795 PMC: 9872005. DOI: 10.3389/fonc.2022.974654.

Human α-defensin 6 (HD6) suppresses CRC proliferation and metastasis through abolished EGF/EGFR signaling pathway.

Wei P, Lin J, Hung C, Makondi P, Batzorig U, Chang T Int J Med Sci. 2022; 19(1):34-46.

PMID: 34975297 PMC: 8692109. DOI: 10.7150/ijms.64850.

Gene Expression Changes Accompanying the Duodenal Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis.

Thiruvengadam S, OMalley M, LaGuardia L, Lopez R, Wang Z, Shadrach B Clin Transl Gastroenterol. 2019; 10(6):e00053.

PMID: 31211760 PMC: 6613862. DOI: 10.14309/ctg.0000000000000053.

Multifaceted immune functions of human defensins and underlying mechanisms.

Fruitwala S, El-Naccache D, Chang T Semin Cell Dev Biol. 2018; 88:163-172.

PMID: 29501617 PMC: 6485945. DOI: 10.1016/j.semcdb.2018.02.023.

Expression of Antimicrobial Peptides by Uveal and Cutaneous Melanoma Cells and Investigation of Their Role in Tumor Cell Migration and Vasculogenic Mimicry.

Manarang J, Otteson D, McDermott A Curr Eye Res. 2017; 42(11):1474-1481.

PMID: 28910167 PMC: 6141659. DOI: 10.1080/02713683.2017.1339806.

References

Radeva M, Hofmann T, Altenberg B, Mothes H, Richter K, Pool-Zobel B . The database dbEST correctly predicts gene expression in colon cancer patients. Curr Pharm Biotechnol. 2008; 9(6):510-5. DOI: 10.2174/138920108786786330. View

Zou H, Harrington J, Sugumar A, Klatt K, Smyrk T, Ahlquist D . Detection of colorectal disease by stool defensin assay: an exploratory study. Clin Gastroenterol Hepatol. 2007; 5(7):865-8. DOI: 10.1016/j.cgh.2007.03.013. View

Cunliffe R, Kamal M, Rose F, James P, Mahida Y . Expression of antimicrobial neutrophil defensins in epithelial cells of active inflammatory bowel disease mucosa. J Clin Pathol. 2002; 55(4):298-304. PMC: 1769631. DOI: 10.1136/jcp.55.4.298. View

Kuwano K, Tanaka N, Shimizu T, Kida Y . Antimicrobial activity of inducible human beta defensin-2 against Mycoplasma pneumoniae. Curr Microbiol. 2006; 52(6):435-8. DOI: 10.1007/s00284-005-0215-7. View

Cunliffe R, Mahida Y . Expression and regulation of antimicrobial peptides in the gastrointestinal tract. J Leukoc Biol. 2003; 75(1):49-58. DOI: 10.1189/jlb.0503249. View

Daher K, Lehrer R, Ganz T, Kronenberg M . Isolation and characterization of human defensin cDNA clones. Proc Natl Acad Sci U S A. 1988; 85(19):7327-31. PMC: 282179. DOI: 10.1073/pnas.85.19.7327. View

Albrethsen J, Bogebo R, Gammeltoft S, Olsen J, Winther B, Raskov H . Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours: a biomarker study. BMC Cancer. 2005; 5:8. PMC: 548152. DOI: 10.1186/1471-2407-5-8. View

Hiyama T, Yokozaki H, Kitadai Y, Tahara H, Ide T, Haruma K . In situ mRNA hybridization technique for analysis of human telomerase RNA in gastric precancerous and cancerous lesions. Jpn J Cancer Res. 1999; 89(11):1187-94. PMC: 5921710. DOI: 10.1111/j.1349-7006.1998.tb00514.x. View

Lundy F, Orr D, Gallagher J, Maxwell P, Shaw C, Napier S . Identification and overexpression of human neutrophil alpha-defensins (human neutrophil peptides 1, 2 and 3) in squamous cell carcinomas of the human tongue. Oral Oncol. 2003; 40(2):139-44. DOI: 10.1016/s1368-8375(03)00142-8. View

10.

Melle C, Ernst G, Schimmel B, Bleul A, Thieme H, Kaufmann R . Discovery and identification of alpha-defensins as low abundant, tumor-derived serum markers in colorectal cancer. Gastroenterology. 2005; 129(1):66-73. DOI: 10.1053/j.gastro.2005.05.014. View

11.

Zhang K, Lu Q, Zhang Q, Hu X . Regulation of activities of NK cells and CD4 expression in T cells by human HNP-1, -2, and -3. Biochem Biophys Res Commun. 2004; 323(2):437-44. DOI: 10.1016/j.bbrc.2004.08.111. View

12.

Hill C, Yee J, Selsted M, Eisenberg D . Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilization. Science. 1991; 251(5000):1481-5. DOI: 10.1126/science.2006422. View

13.

Arango D, Mariadason J, Wilson A, Yang W, Corner G, Nicholas C . c-Myc overexpression sensitises colon cancer cells to camptothecin-induced apoptosis. Br J Cancer. 2003; 89(9):1757-65. PMC: 2394410. DOI: 10.1038/sj.bjc.6601338. View

14.

Muller C, Markovic-Lipkovski J, Klatt T, Gamper J, Schwarz G, Beck H . Human alpha-defensins HNPs-1, -2, and -3 in renal cell carcinoma: influences on tumor cell proliferation. Am J Pathol. 2002; 160(4):1311-24. PMC: 1867209. DOI: 10.1016/s0002-9440(10)62558-8. View

15.

Nam M, Kee M, Kuick R, Hanash S . Identification of defensin alpha6 as a potential biomarker in colon adenocarcinoma. J Biol Chem. 2004; 280(9):8260-5. DOI: 10.1074/jbc.M410054200. View

16.

Menendez A, Finlay B . Defensins in the immunology of bacterial infections. Curr Opin Immunol. 2007; 19(4):385-91. DOI: 10.1016/j.coi.2007.06.008. View

17.

Andreu P, Colnot S, Godard C, Gad S, Chafey P, Niwa-Kawakita M . Crypt-restricted proliferation and commitment to the Paneth cell lineage following Apc loss in the mouse intestine. Development. 2005; 132(6):1443-51. DOI: 10.1242/dev.01700. View

18.

Albrethsen J, Moller C, Olsen J, Raskov H, Gammeltoft S . Human neutrophil peptides 1, 2 and 3 are biochemical markers for metastatic colorectal cancer. Eur J Cancer. 2006; 42(17):3057-64. DOI: 10.1016/j.ejca.2006.05.039. View

19.

Holterman D, Diaz J, Blackmore P, Davis J, Schellhammer P, Corica A . Overexpression of alpha-defensin is associated with bladder cancer invasiveness. Urol Oncol. 2006; 24(2):97-108. DOI: 10.1016/j.urolonc.2005.07.010. View