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

• We describe here an assay for the detection of loss of heterozygosity at this locus using two dinucleotide repeat polymorphisms identified in WFDC1 introns, with a combined informativity of 86% [9].
• WFDC1 is a recently isolated human gene identified as a tumour suppressor gene candidate [9].
• The WFDC1 gene maps in human chromosome 16q24, an area of frequent loss of heterozygosity (LOH) in several tumour types, in particular in hepatocellular carcinoma (HCC) [9].
• We, therefore, propose that WFDC1/ps20 may not be a classical tumor suppressor gene, but might play a role in the maintenance of the normal extra cellular matrix milieu in the prostate [8].
• Quantitative RT-PCR demonstrated significant down regulation of WFDC1/ps20 in prostate tumors [8].

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].

References