Serum protein signature may improve detection of ductal carcinoma in situ of the breast

Abstract

Ductal carcinoma in situ (DCIS) of the breast is part of a spectrum of preinvasive lesions that originate within normal breast tissue and progress to invasive breast cancer. The detection of DCIS is important for the reduction of mortality from breast cancer, but the diagnosis of preinvasive breast tumors is hampered by the lack of an adequate detection method. To identify the changes in protein expression during the initial stage of tumorigenesis and to identify the presence of new DCIS markers, we analysed serum from 60 patients with breast cancer and 60 normal controls using mass spectrometry. A 23-protein index was generated that correctly distinguishes the DCIS and control groups with sensitivities and specificities in excess of 80% in two independent cohorts. Two candidate peptides were purified and identified as platelet factor 4 (PF-4) and complement C3a desArg anaphylatoxin (C3a desArg ) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In an independent serum set of 165 patients, PF-4 and C3a desArg were significantly upregulated in DCIS compared with non-cancerous controls, as validated using western blot and enzyme-linked immunosorbent assay. We conclude that our serum protein-based test, used in conjunction with image-based screening practices, could improve the sensitivity and specificity of breast cancer detection.

International Union of Basic and Clinical Pharmacology. LXXXVII. Complement Peptide C5a, C4a, and C3a Receptors

“…Examples are the increased serum levels of C3a that indicate the presence of colorectal tumors (Habermann et al, 2006), hepatitis C virus-related hepatocellular carcinoma (Lee et al, 2006a;Kanmura et al, 2010), benign prostatic hyperplasia (Xie et al, 2011), and ductal carcinoma in situ of the breast (Solassol et al, 2010). C4a has recently been shown to be elevated in patients with chronic hepatitis C infection and active disease but is even higher in infected but asymptomatic individuals (Imakiire et al, 2012).…”

Identification of Potential Markers Related to Neoadjuvant Chemotherapy Sensitivity of Breast Cancer by SELDI-TOF MS

“…[23] Moreover, there were similar peaks between our results and what reported previously on serum samples (approximate registered m/z values 2,742, 3,992, 5,877, 6,489,8,888,8,931,8,942, and 8,973 Da). [24] Notably, protein peak at 8.9 kDa has been reported in numerous previous studies, [17,18,[20][21][22][23][24][25] indicating its potential values in the diagnosis of breast cancer and the evaluation of treatments and NACT.…”

“…[17,18]. Briefly, proteins were extracted from the tumor samples and separated on 16% Tris-glycine sodium dodecyl sulfate-polyacrylamide gels electrophoresis (SDS-PAGE), and subsequently transferred onto polyvinylidene fluoride membranes.…”

Early diagnostic protein biomarkers for breast cancer: how far have we come?

“…C3a des-arginine anaphylatoxin Levels of C3a desArg (molecular weight: 8,938 Da) were higher in breast cancer cases compared to healthy controls in six studies [19][20][21][22][23][24], while in two other studies lower levels were found in breast cancer cases [25,26]. These two studies investigated the same group of breast cancer cases and healthy controls [25,26], which was extended with about 100 cases and 80 controls in the most recent study [25].…”