Complement C3f serum levels may predict breast cancer risk in women with gross cystic disease of the breast

Mangerini, Rosa; Rubagotti, Alessandra; Romano, Paolo; Damonte, Gianluca; Guglielmini, Pamela; Facchiano, Angelo; Ferri, F.; Ricci, Francesco; Rocco, Mattia; Boccardo, Francesco

doi:10.1016/j.jprot.2013.04.029

Cited by 19 publications

(21 citation statements)

References 27 publications

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“…Perhaps most striking, the peptide species C3f_R 1310 -L 1319 , C3f_R 1309 -L 1319 , C3f_R 1308 -L 1319 , C3f_R 1305 -L 1319 , and C3f_R 1304 -L 1319 presented prominently in samples of BC-I and BC-II, compared to the healthy cohort ( p < 0.001) (Fig. 6), consistent with the report by Profumo et al (13). Overall, the patterns of these CPN-catalyzed products in the clinical samples from breast cancer patients matched strongly with our observations in the breast cancer mouse model.…”

Section: Resultssupporting

confidence: 91%

“…An additional advantage of scouring blood samples for this type of information is its accessibility, while being less prone to selection bias compared to tissue samples. Indeed, several studies have presented comprehensive qualitative and quantitative profiling of circulating peptides, demonstrating their enormous potential use as a rapid, cost-effective, and accurate platform for cancer diagnosis and therapeutic evaluation, even despite the complexity cancer pathophysiology landscape (9–13). However, only a few of them have shown a direct correlation between the presence (and/or quantity) of these circulating peptides, the proteases/peptidases that generate them, or the roles these play in cancer progression (12, 14–16).…”

Section: Introductionmentioning

confidence: 99%

“…C3f_S 1304 -R 1320 has also been reported as a substrate of CPN in an in-vitro study (22). Villanuva and Profumo have both attributed several daughter fragments of C3f_S 1304 -R 1320 and BK 9 to human bladder cancer, prostate cancer and breast cancer (12, 13). Given these results, the only that we could identify that attempts to draw a relationship between CPN and cancer is study conducted decades ago in 1983, where the investigators showed that increased CPN activity was observed in the sera of lung cancer patients (23).…”

Section: Introductionmentioning

confidence: 99%

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Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

Chen

et al. 2014

Clinical Chemistry

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Background Carboxypeptidase N (CPN) plays an important role in regulating vasoactive peptide hormones, growth factors, and cytokines by specifically cleaving their C-terminal basic residues. Herein we demonstrated that the circulating peptides specifically cleaved by CPN in the tumor microenvironment can indeed be stage-specific indicators of breast cancer. Methods The activity of CPN was evaluated using an ex-vivo peptide cleavage assay, in which synthesized C3f peptide (His6-C3f_S1304-R1320-His6) is incubated in interstitial fluids of breast tumor and adjacent normal breast tissues in mice with orthotopic implantation of the human cell line MDA-MB-231. Fragment profiling, by an approach combining nanopore fractionation and mass spectrometry, revealed the nature and extent of cleavage by CPN. These results correlated with the level of CPN-catalyzed peptides in blood specimens taken from the tumor-bearing mice, healthy women and breast cancer patients. CPN expression in the same set of samples was further examined by immunohistochemistry and immunoblotting. Results We showed that generation of C3f_R1310-L1319 specifically correlated with the CPN expression level. In both the mouse and clinical patient samples, the amount of CPN was clearly increased in tumor tissues compared to that seen in normal breast tissue, while its counterpart in blood remained constant. The amount of 6 CPN-catalyzed peptides predominantly increased in sera taken from the mice (n=8) at 2 weeks after orthotropic implantation. Six homologous peptides displayed the significantly higher expression in the patients’ plasma as early as the first pathologic stage of breast cancer. Conclusions The amount of circulating CPN-catalyzed peptides reported here reflects the extent of this enzyme’s activity in tumors, and our results clearly indicate their strong potential as biomarkers for non-invasive and early diagnosis of breast cancer.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

Chen

et al. 2014

Clinical Chemistry

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“…C3f was found over-expressed in several cancers [26][27][28][29], but it has never been associated to the onset of the PCa. The identified C3f fragment is generated by an alteration of the C3-guided complement system and, specifically, by an altered C3b inactivation pathway, which bears to protein fragmentation.…”

Section: Discussionmentioning

confidence: 99%

A PSA-guided approach for a better diagnosis of prostatic adenocarcinoma based on MALDI profiling and peptide identification

Fania¹,

Sogno²,

Vasso³

et al. 2015

Clinica Chimica Acta

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“…Specifically, our results indicate that complement C3f and Fibrinopeptide A (FPA) are potentially noninvasive biomarkers for identifying patients with NAFLD. Though complement C3f and FPA have been found to be associated with some diseases, such as cognitive dysfunction in elderly patients and breast cancer[42], [43], and complement C3f has been reported to be associated with HCC[44], the association between these two complements and the risk for incidental NAFLD have not yet been reported. Without data concerning the severity (in terms of inflammation and fibrosis) of NAFLD in our patients, the possible role of complement C3f and FPA cannot be completely documented.…”

Section: Discussionmentioning

confidence: 99%

Serum Complement C3f and Fibrinopeptide A Are Potential Novel Diagnostic Biomarkers for Non-Alcoholic Fatty Liver Disease: A Study in Qingdao Twins

et al. 2014

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AimsTo compare the different serum peptidome patterns between twins with and without non-alcoholic fatty liver disease (NAFLD) in order to help understand the pathogenesis of NAFLD and to identify potential diagnostic and therapeutic targets.MethodsThe peptidomics patterns of 63 cases with NAFLD were compared with their twin healthy controls in Qingdao, China. Peptides between 800Da and 3500Da were captured and concentrated using C18 reversed-phase columns, followed by MALDI-TOF mass spectrometry. The sequences of peptides associated with NAFLD were further identified by MALDI-TOF-TOF. Further validation studies were conducted. One hundred additional serum samples were detected by commercially available ELISA kits to calculate the concentrations of complement C3f and fibrinopeptide A, respectively. The differences of these two peptides in the NAFLD and control groups were compared using SPSS 17.0, respectively.ResultsCompared with healthy controls, eleven peaks (861.1, 877.07, 904.5, 1206.57, 1350.64, 1518.7, 1690.9, 1777.94, 2931.29, 3190.4, 3261.4) were up-regulated and 7 peaks (942.44, 1020.47, 1060.06, 1211.7, 1263.63, 1449.76, 2768.3) were down-regulated in the NAFLD group. Two peptides derived from complement C3f and fibrinopeptide A, respectively, had the highest ROC values indistinguishing NAFLD cases from their normal controls. In the validation group, the concentrations of complement C3f and fibrinopeptide A (1466.929±78.306 pg/ml, 4.189±0.326 ng/ml, respevtively) in NAFLD group was higher than in control group (complement C3f 1159.357±99.624 pg/ml, FPA 3.039±0.483 ng/ml; P<0.05).ConclusionsIn this study, we established apeptidomics pattern that could help distinguish NAFLD patients from their twin controls. The differently-regulated peptides identified in our study may be potential diagnostic markers or therapeutic targets for NAFLD.

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Complement C3f serum levels may predict breast cancer risk in women with gross cystic disease of the breast

Cited by 19 publications

References 27 publications

Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer

A PSA-guided approach for a better diagnosis of prostatic adenocarcinoma based on MALDI profiling and peptide identification

Serum Complement C3f and Fibrinopeptide A Are Potential Novel Diagnostic Biomarkers for Non-Alcoholic Fatty Liver Disease: A Study in Qingdao Twins

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