Tumor Biology

, Volume 35, Issue 1, pp 123–127 | Cite as

Abnormal hypermethylation and clinicopathological significance of FBLN1 gene in cutaneous melanoma

  • Bao-Jin Wu
  • Zhao-Ping Zhou
  • Wen-Peng Li
  • Wei Ding
  • Ying-Zhi Wu
  • Zhong-Wen Zhou
  • Rong-Qing Zhang
  • Qing-Feng Liu
  • Hua Jiang
Research Article


Fibulin-1 (FBLN1) is involved in the progression of some types of cancer. However, the role of FBLN1 in cutaneous melanoma (CM) has not been examined. The purpose of this study was to understand the molecular mechanisms and clinical significance of FBLN1 inactivation in CM. The expression of FBLN1 mRNA in CM tissues and adjacent normal skin tissues was analyzed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Methylation-specific polymerase chain reaction was performed to examine the methylation status of the FBLN1 gene promoter. Furthermore, the methylation status of FBLN1 was analyzed with the clinicopathological characteristics and overall survival. qRT-PCR showed FBLN1 mRNA levels in cancerous tissues to be significantly decreased compared with that in adjacent normal skin tissues. The rate of FBLN1 promoter methylation was significantly higher in CM tissues than in adjacent normal skin tissues (P < 0.001). Downregulation of FBLN1 was strongly correlated with promoter methylation (P = 0.021). Promoter hypermethylation of FBLN1 was significantly associated with tumor stage (P = 0.019). In addition, FBLN1 methylation status was associated with significantly shorter survival time and was an independent predictor of overall survival. In conclusion, our results indicated that FBLN1 is a novel candidate of tumor suppressor gene and that promoter hypermethylation of FBLN1 is associated with tumor progression in CM.


FBLN1 Methylation MSP Prognosis 



This work was funded by research grants from the Shanghai Health Bureau (no. 20114211), China.

Conflicts of interest



  1. 1.
    Marks R. Epidemiology of melanoma. Clin Exp Dermatol. 2000;25:459–63.PubMedCrossRefGoogle Scholar
  2. 2.
    Kobayashi N, Kostka G, Garbe JH, Keene DR, Bächinger HP, Hanisch FG, et al. A comparative analysis of the fibulin protein family. Biochemical characterization, binding interactions, and tissue localization. J Biol Chem. 2007;282:11805–16.PubMedCrossRefGoogle Scholar
  3. 3.
    Pupa SM, Giuffré S, Castiglioni F, Bertola L, Cantú M, Bongarzone I, et al. Regulation of breast cancer response to chemotherapy by fibulin-1. Cancer Res. 2007;67:4271–7. doi: 10.1158/0008-5472.CAN-06-4162.PubMedCrossRefGoogle Scholar
  4. 4.
    Morrissey C, True LD, Roudier MP, Coleman IM, Hawley S, Nelson PS, et al. Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases. Clin Exp Metastasis. 2008;25:377–88.PubMedCrossRefGoogle Scholar
  5. 5.
    Moll F, Katsaros D, Lazennec G, Hellio N, Roger P, Giacalone PL, et al. Estrogen induction and overexpression of fibulin-1C mRNA in ovarian cancer cells. Oncogene. 2002;21:1097–107. doi: 10.1038/sj/onc/1205178.PubMedCrossRefGoogle Scholar
  6. 6.
    Cheng YY, Jin H, Liu X, Siu JM, Wong YP, Ng EK, et al. Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer. Br J Cancer. 2008;99:2083–7. doi: 10.1038/sj.bjc.6604760.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Kanda M, Nomoto S, Okamura Y, Hayashi M, Hishida M, Fujii T, et al. Promoter hypermethylation of fibulin 1 gene is associated with tumor progression in hepatocellular carcinoma. Mol Carcinog. 2011;50:571–9. doi: 10.1002/mc.20735.PubMedCrossRefGoogle Scholar
  8. 8.
    Xiao W, Wang J, Li H, Guan W, Xia D, Yu G, et al. Fibulin-1 is down-regulated through promoter hypermethylation and suppresses renal cell carcinoma progression. J Urol. 2013;190:291–301. doi: 10.1016/j.juro.2013.01.098.PubMedCrossRefGoogle Scholar
  9. 9.
    Peng H, Long F, Wu Z, Chu Y, Li J, Kuai R, et al. Downregulation of DLC-1 gene by promoter methylation during primary colorectal cancer progression. Biomed Res Int. 2013;2013:181384. doi: 10.1155/2013/181384.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Shin SH, Park SY, Kang GH. Down-regulation of dual-specificity phosphatase 5 in gastric cancer by promoter CpG island hypermethylation and its potential role in carcinogenesis. Am J Pathol. 2013;182:1275–85. doi: 10.1016/j.ajpath.2013.01.004.PubMedCrossRefGoogle Scholar
  11. 11.
    Yoo TH, Ryu BK, Lee MG, Chi SG. CD81 is a candidate tumor suppressor gene in human gastric cancer. Cell Oncol (Dordr). 2013;36:141–53. doi: 10.1007/s13402-012-0119-z.CrossRefGoogle Scholar
  12. 12.
    Zhong X, Zhu Y, Mao J, Zhang J, Zheng S. Frequent epigenetic silencing of PCDH10 by methylation in human colorectal cancer. J Cancer Res Clin Oncol. 2013;139:485–90. doi: 10.1007/s00432-012-1353-5.PubMedCrossRefGoogle Scholar
  13. 13.
    Timpl R, Sasaki T, Kostka G, Chu ML. Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol. 2003;4:479–89. doi: 10.1038/nrm1130.PubMedCrossRefGoogle Scholar
  14. 14.
    Burstein HJ, Schwartz RS. Molecular origins of cancer. N Engl J Med. 2008;358:527. doi: 10.1056/NEJMe0800065.PubMedCrossRefGoogle Scholar
  15. 15.
    Issa JP. CpG island methylator phenotype in cancer. Nat Rev Cancer. 2004;4:988–93. doi: 10.1038/nrc1507.PubMedCrossRefGoogle Scholar
  16. 16.
    Anglim PP, Alonzo TA, Laird-Offringa IA. DNA methylation-based biomarkers for early detection of non-small cell lung cancer: an update. Mol Cancer. 2008;7:81. doi: 10.1186/1476-4598-7-81.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Bao-Jin Wu
    • 1
  • Zhao-Ping Zhou
    • 1
  • Wen-Peng Li
    • 2
  • Wei Ding
    • 1
  • Ying-Zhi Wu
    • 3
  • Zhong-Wen Zhou
    • 4
  • Rong-Qing Zhang
    • 5
  • Qing-Feng Liu
    • 6
  • Hua Jiang
    • 7
  1. 1.Department of Plastic Surgery, Huashan HospitalFudan UniversityShanghaiChina
  2. 2.Department of Plastic Surgery, the Second Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  3. 3.Department of Dermatology, Huashan HospitalFudan UniversityShanghaiChina
  4. 4.Department of Pathology, Huashan HospitalFudan UniversityShanghaiChina
  5. 5.Fudan University Shanghai Cancer CenterShanghaiChina
  6. 6.Department of Pharmacy, Huashan HospitalFudan UniversityShanghaiChina
  7. 7.Department of Plastic Surgery, Changzheng HospitalSecond Military Medical UniversityShanghaiChina

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