Downregulation of C3 and C4A/B complement factor fragments in plasma from patients with squamous cell carcinoma of the penis

Purpose To investigate the use of ClinProt technique to identify cancer markers in plasma of patients suffering from squamous cell carcinoma of the penis (SCCP). Materials and Methods Plasma of 36 healthy subjects and 25 patients with penile carcinoma who underwent surgical treatment between June 2010 and June 2011 was collected and analyzed by the ClinProt/MALDI/ToF technique. Then the peptides were identified from the C8 MB eluted fraction of patients' and control subjects' plasma by LIFT MS/MS. Results A cluster of 2 peptides (A=m/z 1897.22 ± 9 Da and B=m/z 2021.99 ± 9 Da) was able to discriminate patients from control subjects. Cross validation analysis using the whole casuistic showed 62.5% and 86.76% sensitivity and specificity, respectively. The cluster also showed very high sensitivity (100%) and specificity (97%) for SCCP patients that died due to the disease. Furthermore, patients with lymph node involvement presented sensitivity and specificity of 80% and 97%, respectively. These two peptides were identified by the proteomic approach based on a MALDI-TOF/TOF as fragments of C3 (m/z 1896.17) and C4a/b (m/z 2021.26) complement proteins. Conclusions The results showed that as the disease progresses, the fragments C3 and C4 A/B are less expressed in comparison with healthy subjects. These results may be useful as prognostic tools

Cell-Autonomous and Non-Cell-Autonomous Roles for <em>Irf6</em> during Development of the Tongue

<div><p>Interferon regulatory factor 6 (<i>IRF6</i>) encodes a highly conserved helix-turn-helix DNA binding protein and is a member of the interferon regulatory family of DNA transcription factors. Mutations in <i>IRF6</i> lead to isolated and syndromic forms of cleft lip and palate, most notably Van der Woude syndrome (VWS) and Popliteal Ptyerigium Syndrome (PPS). Mice lacking both copies of <i>Irf6</i> have severe limb, skin, palatal and esophageal abnormalities, due to significantly altered and delayed epithelial development. However, a recent report showed that <i>MCS9.7</i>, an enhancer near <i>Irf6</i>, is active in the tongue, suggesting that <i>Irf6</i> may also be expressed in the tongue. Indeed, we detected Irf6 staining in the mesoderm-derived muscle during development of the tongue. Dual labeling experiments demonstrated that Irf6 was expressed only in the <i>Myf5</i>+ cell lineage, which originates from the segmental paraxial mesoderm and gives rise to the muscles of the tongue. Fate mapping of the segmental paraxial mesoderm cells revealed a cell-autonomous <i>Irf6</i> function with reduced and poorly organized <i>Myf5</i>+ cell lineage in the tongue. Molecular analyses showed that the <i>Irf6</i>−/− embryos had aberrant cytoskeletal formation of the segmental paraxial mesoderm in the tongue. Fate mapping of the cranial neural crest cells revealed non-cell-autonomous <i>Irf6</i> function with the loss of the inter-molar eminence. Loss of <i>Irf6</i> function altered <i>Bmp2</i>, <i>Bmp4</i>, <i>Shh</i>, and <i>Fgf10</i> signaling suggesting that these genes are involved in Irf6 signaling. Based on these data, <i>Irf6</i> plays important cell-autonomous and non-cell-autonomous roles in muscular differentiation and cytoskeletal formation in the tongue.</p> </div