WFDC2 (HE4): A potential role in the innate immunity of the oral cavity and respiratory tract and the development of adenocarcinomas of the lung

Abstract

Background: The Whey Acidic Protein domain is an evolutionarily conserved motif found in a number of proteins, the best studied of which are antiproteinases involved in the innate immune defence of multiple epithelia. We recently characterised the WFDC2 gene which encodes a two WAP domain-containing protein, initially suggested as a marker for epididymis, and showed that it is highly expressed in the lung and salivary gland. The precise location of WFDC2 protein in these sites has not been described.

Characterisation and expression of SPLUNC2, the human orthologue of rodent parotid secretory protein

“…It is interesting that these two related proteins, which presumably share common functional activities, should be expressed in this manner. This observation is not unique for members of the PLUNC family however, as we have previously shown a similar discordant localisation of two other putative innate immune molecules, secretory leukocyte proteinase inhibitor (SLPI) and HE4 (Bingle et al 2006). These are members of the WFDC-domain containing protein (Bingle & Vayarkarnam 2008).…”

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

“…HE4 protein is detected in upper airway epithelial cells as well as in mucous cells and ducts of submucosal glands. Intense immunohistochemical staining is observed in major salivary glands and in minor glands of the nose, sinuses, posterior tongue, and tonsil [78].…”

“…An increase of average HE4 levels in patents with lung cancers was reported [78,80]. HE4 expression has been demonstrated in several lung cancer cell lines [9,79].…”

“…An increasing number of HE4-secreting cells were found in the chronically inflamed lungs [78]. Liu et al measured the serum HE4 level of 114 patients with pulmonary tuberculosis (PTB) and 24 patients with pneumonia [79].…”

Serum Human Epididymis Protein 4 (HE4) As A Diagnostic And Follow-Up Biomarker in Patients With Non-Small Cell Lung Cancer

“…Indeed, WFDC2 is strongly expressed in a wide range of normal human tissues, including trachea, salivary glands, lung, prostate, pituitary gland, thyroid and kidney. 6,9,10 In this study, we aimed to evaluate both the diagnostic performance and the post-resection progress of serum HE4 in patients with NSCLC.…”