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Gene Review

WFDC1  -  WAP four-disulfide core domain 1

Homo sapiens

Synonyms: PS20, Prostate stromal protein ps20, WAP four-disulfide core domain protein 1, ps20 growth inhibitor
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Disease relevance of WFDC1

  • Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival [1].
  • The WFDC1 gene was mapped by FISH analysis to human Chromosome (Chr) 16q24, an area of frequent loss of heterozygosity (LOH) previously identified in multiple cancers including prostate, breast, hepatocellular, and Wilms' tumor [2].
  • However, the intensity of dyspnea caused by histamine-induced bronchoconstriction was lower than that caused by asthma exacerbation (PS20: 1.6 +/- 1.1 vs 2.8 +/- 2.5, respectively, P = .004; deltaBorg/deltaFEV1: 0.08 +/- 0.05 vs 0.21 +/- 0.28, respectively, P = .001) [3].

High impact information on WFDC1

  • Cadherin 13 (CDH13), CBFA2T3, and WFDC1, which are candidate suppressors in other tumor entities with 16q24 loss, did not show loss of expression [4].
  • Our laboratory isolated and identified previously the ps20 protein (WFDC1 gene) as a prostate stromal cell secreted protein [5].
  • Breathlessness perception was evaluated by Borg's scale during methacholine (M) challenge, and PS20 (the perception score obtained when FEV1 fell by 20%) was recorded [6].
  • RESULTS: When pressure support was reduced from PS20 to PS10 the respiratory rate (f) and the rapid shallow breathing index (f/VT) significantly increased and tidal volume (VT) significantly decreased [7].
  • METHODS: DNA from 21 prostate cancer patients and 5 prostate cancer cell lines was screened for mutations in the WFDC1/ps20 gene by sequencing PCR products of each exon [8].

Biological context of WFDC1


Associations of WFDC1 with chemical compounds

  • 4. 4. The PS20 was increased by labetalol 400 mg (P < 0.05) [10].
  • 2. The doses of phenylephrine required to increase systolic BP by 20 mm Hg (PS20) were calculated using a quadratic fit to the individual dose-response curves [11].
  • The dose ratios for PS20 (means +/- s.d.) were: dilevalol 200 mg 1.1 +/- 0.1, labetalol 400 mg 2.2 +/- 0 [12].
  • 9. 6. The PS20 and PD20 of angiotensin II were unchanged by any of the drugs [12].
  • Short- and long-term use of salmeterol did not change significantly the PS20 compared with placebo (p>0.05) in either group (with or without corticosteroid) [13].

Other interactions of WFDC1

  • Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma [9].
  • Responders and nonresponders could be separated by the response of VO2, VT and F to a change in PS 10 to PS 20 cmH2O [14].
  • Increased levels of cystatin C and beta-2-microglobulin in conditioned media from p21-expressing cells was confirmed by antibody capture experiments using anticystatin C and anti-beta-2-microglobulin antibodies on preactivated PS-20 arrays [15].

Analytical, diagnostic and therapeutic context of WFDC1

  • Quantitative RT-PCR analysis of WFDC1/ps20 was performed in a separate cohort of matched tumor/benign tissues [8].
  • Decreased stromal WFDC1/ps20 expression correlated with higher radical prostatectomy Gleason scores, positive surgical margins, extracapsular extension, higher clinical stage, and higher preoperative prostate specific antigen levels [1].
  • Expression of WFDC1/ps20 in different tissue types was examined by Northern blot and by PCR across a multi-tissue cDNA panel [8].
  • The expression of C3a in HCC sera was further validated by PS20 chip immunoassay and Western blotting [16].


  1. Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival. McAlhany, S.J., Ayala, G.E., Frolov, A., Ressler, S.J., Wheeler, T.M., Watson, J.E., Collins, C., Rowley, D.R. Prostate (2004) [Pubmed]
  2. The WFDC1 gene encoding ps20 localizes to 16q24, a region of LOH in multiple cancers. Larsen, M., Ressler, S.J., Gerdes, M.J., Lu, B., Byron, M., Lawrence, J.B., Rowley, D.R. Mamm. Genome (2000) [Pubmed]
  3. Perception of dyspnea during exacerbation and histamine-related bronchoconstriction in patients with asthma. Ekici, M., Ekici, A., Kara, T., Keles, H., Karlidag, A., Altunkaya, V., Bulcun, E. Ann. Allergy Asthma Immunol. (2006) [Pubmed]
  4. Allelic loss in a minimal region on chromosome 16q24 is associated with vitreous seeding of retinoblastoma. Gratias, S., Rieder, H., Ullmann, R., Klein-Hitpass, L., Schneider, S., B??l??ni, R., Kappler, M., Lohmann, D.R. Cancer Res. (2007) [Pubmed]
  5. Promotion of angiogenesis by ps20 in the differential reactive stroma prostate cancer xenograft model. McAlhany, S.J., Ressler, S.J., Larsen, M., Tuxhorn, J.A., Yang, F., Dang, T.D., Rowley, D.R. Cancer Res. (2003) [Pubmed]
  6. Personality profiles and breathlessness perception in outpatients with different gradings of asthma. Chetta, A., Gerra, G., Foresi, A., Zaimovic, A., Del Donno, M., Chittolini, B., Malorgio, R., Castagnaro, A., Olivieri, D. Am. J. Respir. Crit. Care Med. (1998) [Pubmed]
  7. Changes in occlusion pressure (P0.1) and breathing pattern during pressure support ventilation. Perrigault, P.F., Pouzeratte, Y.H., Jaber, S., Capdevila, X.J., Hayot, M., Boccara, G., Ramonatxo, M., Colson, P. Thorax (1999) [Pubmed]
  8. Molecular analysis of WFDC1/ps20 gene in prostate cancer. Watson, J.E., Kamkar, S., James, K., Kowbel, D., Andaya, A., Paris, P.L., Simko, J., Carroll, P., McAlhany, S., Rowley, D., Collins, C. Prostate (2004) [Pubmed]
  9. Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma. Saffroy, R., Riou, P., Soler, G., Azoulay, D., Emile, J.F., Debuire, B., Lemoine, A. Eur. J. Hum. Genet. (2002) [Pubmed]
  10. The dose dependency of the alpha- and beta-adrenoceptor antagonist activity of carvedilol in man. Tham, T.C., Guy, S., McDermott, B.J., Shanks, R.G., Riddell, J.G. British journal of clinical pharmacology. (1995) [Pubmed]
  11. Dose-dependent alpha 1-adrenoceptor antagonist activity of the anti-arrhythmic drug, abanoquil (UK-52,046), without reduction in blood pressure in man. Tham, T.C., Guy, S., Shanks, R.G., Harron, D.W. British journal of clinical pharmacology. (1992) [Pubmed]
  12. The dose dependency of the alpha-adrenoceptor antagonist and beta-adrenoceptor partial agonist activity of dilevalol and labetalol in man. Tham, T.C., McKaigue, J.P., Guy, S., Shanks, R.G., Riddell, J.G. British journal of clinical pharmacology. (1993) [Pubmed]
  13. Influence of beclomethasone and salmeterol on the perception of methacholine-induced bronchoconstriction. Boulet, L.P., Turcotte, H., Cartier, A., Milot, J., Côté, J., Malo, J.L., Laviolette, M. Chest (1998) [Pubmed]
  14. Tidal volume, breathing frequency, and oxygen consumption at different pressure support levels in the early stage of weaning in patients without chronic obstructive pulmonary disease. Hörmann, C., Baum, M., Luz, G., Putensen, C., Putz, G. Intensive care medicine. (1992) [Pubmed]
  15. Proteomic analysis of factors released from p21-overexpressing tumour cells. Currid, C.A., O'Connor, D.P., Chang, B.D., Gebus, C., Harris, N., Dawson, K.A., Dunn, M.J., Pennington, S.R., Roninson, I.B., Gallagher, W.M. Proteomics (2006) [Pubmed]
  16. Identification of complement C3a as a candidate biomarker in human chronic hepatitis C and HCV-related hepatocellular carcinoma using a proteomics approach. Lee, I.N., Chen, C.H., Sheu, J.C., Lee, H.S., Huang, G.T., Chen, D.S., Yu, C.Y., Wen, C.L., Lu, F.J., Chow, L.P. Proteomics (2006) [Pubmed]
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