Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Prognostic Significance of Desmoglein 2 and Desmoglein 3 in Esophageal Squamous Cell Carcinoma

  • Fang, Wang-Kai (Department of Biochemistry and Molecular Biology, Shantou University Medical College) ;
  • Gu, Wei (Department of Biochemistry and Molecular Biology, Shantou University Medical College) ;
  • Liao, Lian-Di (Institute of Oncologic Pathology, Shantou University Medical College) ;
  • Chen, Bo (Institute of Oncologic Pathology, Shantou University Medical College) ;
  • Wu, Zhi-Yong (Department of Oncology Surgery, Affiliated Shantou Hospital of Sun Yat-Sen University) ;
  • Wu, Jian-Yi (Department of Biochemistry and Molecular Biology, Shantou University Medical College) ;
  • Shen, Jian (Institute of Oncologic Pathology, Shantou University Medical College) ;
  • Xu, Li-Yan (The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area) ;
  • Li, En-Min (Department of Biochemistry and Molecular Biology, Shantou University Medical College)
  • Published : 2014.01.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: Desmogleins (DSGs) are major members among the desmosomal cadherins critically involved in cell-cell adhesion and the maintenance of normal tissue architecture in epithelia. Reports exploring links of DSG family member expression with cancers are few and vary. The aim of this study was to investigate the ratio of DSG2 and DSG3 mRNA expression in esophageal squamous cell carcinoma (ESCC) tissue to normal tissue (T/N ratio) and evaluate correlations with clinical parameters. Methods: The mRNA expression of DSGs, as well as ${\gamma}$-catenin and desmoplakin, was detected by real-time quantitative RT-PCR in 85 cases of ESCC tissue specimens. Results: The expression level of DSG3 mRNA was significantly higher than that of DSG2 in ESCC specimens (p=0.000). DSG3 mRNA expression highly correlated with histological grade (p=0.009), whereas that of DSG2 did not significantly relate to any clinicopathologic parameter. Kaplan-Meier survival analysis showed that only DSG3 expression had an impact on the survival curve, with negative DSG3 expression indicating worse survival (p=0.038). Multivariate Cox regression analysis demonstrated DSG3 to be an independent prognostic factor for survival. Furthermore, correlation analysis demonstrated the mRNA level of DSG3 to highly correlate with those of ${\gamma}$-catenin and desmoplakin in ESCC samples (p=0.000), implying that the expression of desmosomal components might be regulated by the same upstream regulatory molecules. Conclusions: Our findings suggest that DSG3 may be involved in the progression of ESCC and serve as a prognostic marker, while expression of DSG2 cannot be used as a predictor of ESCC patient outcome.

Keywords

References

  1. Brennan D, Mahoney MG (2009). Increased expression of Dsg2 in malignant skin carcinomas: A tissue-microarray based study. Cell Adh Migr, 3, 148-54. https://doi.org/10.4161/cam.3.2.7539
  2. Chambers AF, Groom AC, MacDonald IC (2002). Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer, 2, 563-72. https://doi.org/10.1038/nrc865
  3. Chen YJ, Chang JT, Lee L, et al (2007). DSG3 is overexpressed in head neck cancer and is a potential molecular target for inhibition of oncogenesis. Oncogene, 26, 467-76. https://doi.org/10.1038/sj.onc.1209802
  4. Dusek RL, Attardi LD (2011). Desmosomes: new perpetrators in tumour suppression. Nat Rev Cancer, 11, 317-23. https://doi.org/10.1038/nrc3051
  5. Fang WK, Gu W, Li EM, et al (2010). Reduced membranous and ectopic cytoplasmic expression of DSC2 in esophageal squamous cell carcinoma: an independent prognostic factor. Hum Pathol, 41, 1456-65. https://doi.org/10.1016/j.humpath.2010.04.003
  6. Fang WK, Liao LD, Li LY, et al (2013). Down-regulated desmocollin-2 promotes cell aggressiveness through redistributing adherens junctions and activating beta-catenin signalling in oesophageal squamous cell carcinoma. J Pathol, 231, 257-70. https://doi.org/10.1002/path.4236
  7. Fukuoka J, Dracheva T, Shih JH, et al (2007). Desmoglein 3 as a prognostic factor in lung cancer. Hum Pathol, 38, 276-83. https://doi.org/10.1016/j.humpath.2006.08.006
  8. Garrod D, Chidgey M (2008). Desmosome structure, composition and function. Biochim Biophys Acta, 1778, 572-87. https://doi.org/10.1016/j.bbamem.2007.07.014
  9. Gomez-Morales M, Camara-Pulido M, Miranda-Leon MT, et al (2013). Differential immunohistochemical localization of desmosomal plaque-related proteins in non-small-cell lung cancer. Histopathology, 63, 103-13. https://doi.org/10.1111/his.12126
  10. Gornowicz-Porowska J, Bowszyc-Dmochowska M, Seraszek-Jaros A, et al (2011). Loss of correlation between intensities of desmoglein 2 and desmoglein 3 expression in basal cell carcinomas. Acta Dermatovenerol Croat, 19, 150-5.
  11. Green KJ, Simpson CL (2007). Desmosomes: new perspectives on a classic. J Invest Dermatol, 127, 2499-515. https://doi.org/10.1038/sj.jid.5701015
  12. Hartlieb E, Kempf B, Partilla M, et al (2013). Desmoglein 2 is less important than desmoglein 3 for keratinocyte cohesion. PLoS One, 8, e53739. https://doi.org/10.1371/journal.pone.0053739
  13. Ishii K, Norvell SM, Bannon LJ, et al (2001). Assembly of desmosomal cadherins into desmosomes is isoform dependent. J Invest Dermatol, 117, 26-35. https://doi.org/10.1046/j.0022-202x.2001.01400.x
  14. Jeanes A, Gottardi CJ, Yap AS (2008). Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene, 27, 6920-9. https://doi.org/10.1038/onc.2008.343
  15. Kottke MD, Delva E, Kowalczyk AP (2006). The desmosome: cell science lessons from human diseases. J Cell Sci, 119, 797-806. https://doi.org/10.1242/jcs.02888
  16. Kurzen H, Munzing I, Hartschuh W (2003). Expression of desmosomal proteins in squamous cell carcinomas of the skin. J Cutan Pathol, 30, 621-30. https://doi.org/10.1034/j.1600-0560.2003.00122.x
  17. Kyrodimou M, Andreadis D, Drougou A, et al (2013). Desmoglein-3/$\gamma$-catenin and E-cadherin/$\beta$-catenin differential expression in oral leukoplakia and squamous cell carcinoma. Clin Oral Investig,(in press?).
  18. Mariette C, Balon JM, Piessen G, et al (2003). Pattern of recurrence following complete resection of esophageal carcinoma and factors predictive of recurrent disease. Cancer, 97, 1616-23. https://doi.org/10.1002/cncr.11228
  19. Nei H, Saito T, Tobioka H, et al (1996). Expression of component desmosomal proteins in uterine endometrial carcinoma and their relation to cellular differentiation. Cancer, 78, 461-70. https://doi.org/10.1002/(SICI)1097-0142(19960801)78:3<461::AID-CNCR13>3.0.CO;2-X
  20. Papagerakis S, Shabana AH, Pollock BH, et al (2009). Altered desmoplakin expression at transcriptional and protein levels provides prognostic information in human oropharyngeal cancer. Hum Pathol, 40, 1320-9. https://doi.org/10.1016/j.humpath.2009.02.002
  21. Tada H, Hatoko M, Tanaka A, et al (2000). Expression of desmoglein I and plakoglobin in skin carcinomas. J Cutan Pathol, 27, 24-9. https://doi.org/10.1034/j.1600-0560.2000.027001024.x
  22. Teh MT, Parkinson EK, Thurlow JK, et al (2011). A molecular study of desmosomes identifies a desmoglein isoform switch in head and neck squamous cell carcinoma. J Oral Pathol Med, 40, 67-76. https://doi.org/10.1111/j.1600-0714.2010.00951.x
  23. Wang L, Liu T, Wang Y, et al (2007). Altered expression of desmocollin 3, desmoglein 3, and beta-catenin in oral squamous cell carcinoma: correlation with lymph node metastasis and cell proliferation. Virchows Arch, 451, 959-66. https://doi.org/10.1007/s00428-007-0485-5
  24. Wu H, Stanley JR, Cotsarelis G (2003). Desmoglein isotype expression in the hair follicle and its cysts correlates with type of keratinization and degree of differentiation. J Invest Dermatol, 120, 1052-7. https://doi.org/10.1046/j.1523-1747.2003.12234.x
  25. Yashiro M, Nishioka N, Hirakawa K (2006). Decreased expression of the adhesion molecule desmoglein-2 is associated with diffuse-type gastric carcinoma. Eur J Cancer, 42, 2397-403. https://doi.org/10.1016/j.ejca.2006.03.024

Cited by

  1. Desmoglein 3: A Help or a Hindrance in Cancer Progression? vol.7, pp.1, 2015, https://doi.org/10.3390/cancers7010266
  2. Desmoglein-2 is overexpressed in non-small cell lung cancer tissues and its knockdown suppresses NSCLC growth by regulation of p27 and CDK2 vol.143, pp.1, 2017, https://doi.org/10.1007/s00432-016-2250-0
  3. Loss of desmoglein 2 promotes tumorigenic behavior in pancreatic cancer cells vol.56, pp.8, 2017, https://doi.org/10.1002/mc.22644