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

Abstract

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 identifi ed 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 specifi city, respectively. The cluster also showed very high sensitivity (100%) and specifi city (97%) for SCCP patients that died due to the disease. Furthermore, patients with lymph node involvement presented sensitivity and specifi city of 80% and 97%, respectively. These two peptides were identifi ed 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.

Complement anaphylatoxins as immune regulators in cancer

“…In contrast to Corrales et al., who demonstrated elevated levels of circulating C5a, Ornellas et al. demonstrated that C3 and C4a/b fragments were downregulated in the plasma of patients with penile squamous cell carcinoma. These biomarkers had a very high sensitivity and specificity for lymphatic spread and mortality, indicating a close correlation between these fragments and disease progression.…”

A1BG and C3 are overexpressed in patients with cervical intraepithelial neoplasia III

“…Elevated concentrations of complement proteins have been found in the serum of patients with ovarian cancer (43), hepatitis C-associated hepatocellular cancer (44), pancreatic cancer (45), small cell renal carcinoma (46) and SCC (24). In 1980, through simple immunodiffusion assays, Pulay et al (47) demonstrated that the average level of C3 increases with the progression of cervical cancer lesions up to stage III, but diminishes by stage IV (48). In contrast to these previous findings, fragments of C3 and C4 A/B have been reported to be reduced in the plasma of patients with SCC of the penis, and this reduction was found to become more evident as the disease progressed, suggesting that these fragments may be good candidates for prognostic tools (48).…”

“…In 1980, through simple immunodiffusion assays, Pulay et al (47) demonstrated that the average level of C3 increases with the progression of cervical cancer lesions up to stage III, but diminishes by stage IV (48). In contrast to these previous findings, fragments of C3 and C4 A/B have been reported to be reduced in the plasma of patients with SCC of the penis, and this reduction was found to become more evident as the disease progressed, suggesting that these fragments may be good candidates for prognostic tools (48). The cause of this reduction is unknown; however, it may be the result of infection with HPV or the Epstein Barr virus, which are prevalent in this type of cancer in males (49), and whose proteins may be attacking the immune system (50,51).…”

Penis cancer: a case report

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45di sigaretta, le terapie radianti, la balanite xerotica obliterante e la predisposizione genetica [1]. Inoltre c'è una forte evidenza che HPV16 e 18 siano associati all'insorgenza di tumore in oltre il 50% dei casi [2,3].

In Europa e in America la fascia d'età più colpita è quella compresa fra 40 e 70 anni, con un massimo intorno a 55 anni.

INTRODUZIONE

Fra le varie lesioni maligne del pene, quella di gran lunga più frequente è il carcinoma squamoso; tale neoplasia origina preferibilmente, in ordine decrescente di frequenza, in corrispondenza del glande, della superficie interna del prepuzio, del solco balano-prepuziale e, più raramente, del corpo del pene.

Anche se i fattori cancerogeni precisi non sono stati individuati, è stato appurato che le persone circoncise precocemente risultano protette dall'insorgenza del carcinoma; è stato altresì riscontrato che l'incidenza aumenta nel caso di condizioni socio-economiche molto disagiate e, di conseguenza, anche di cattive condizioni igieniche.

…”

“…di sigaretta, le terapie radianti, la balanite xerotica obliterante e la predisposizione genetica [1]. Inoltre c'è una forte evidenza che HPV16 e 18 siano associati all'insorgenza di tumore in oltre il 50% dei casi [2,3].…”