Integrated Proteomic Analysis of Human Cancer Cells and Plasma from Tumor Bearing Mice for Ovarian Cancer Biomarker Discovery

Abstract

BackgroundThe complexity of the human plasma proteome represents a substantial challenge for biomarker discovery. Proteomic analysis of genetically engineered mouse models of cancer and isolated cancer cells and cell lines provide alternative methods for identification of potential cancer markers that would be detectable in human blood using sensitive assays. The goal of this work is to evaluate the utility of an integrative strategy using these two approaches for biomarker discovery.Methodology/Principal FindingsWe investigated a strategy that combined quantitative plasma proteomics of an ovarian cancer mouse model with analysis of proteins secreted or shed by human ovarian cancer cells. Of 106 plasma proteins identified with increased levels in tumor bearing mice, 58 were also secreted or shed from ovarian cancer cells. The remainder consisted primarily of host-response proteins. Of 25 proteins identified in the study that were assayed, 8 mostly secreted proteins common to mouse plasma and human cancer cells were significantly upregulated in a set of plasmas from ovarian cancer patients. Five of the eight proteins were confirmed to be upregulated in a second independent set of ovarian cancer plasmas, including in early stage disease.Conclusions/SignificanceIntegrated proteomic analysis of cancer mouse models and human cancer cell populations provides an effective approach to identify potential circulating protein biomarkers.

Imaging a functional tumorigenic biomarker in the transformed epithelium

“…Quantitative in-depth proteomic profiling by liquid chromatography-mass spectrometry (LC-MS)/ MS was applied to the eight cancer cells lines to measure the levels of matriptase and HAI-1 on the cell surface using a MS2 spectral counting method ( Fig. 2A) (28)(29)(30). Using this approach, the three cell lines that demonstrated probe localization were found to have the highest matriptase protein expression with HT29 possessing the most.…”

Novel automated three‐dimensional genome scanning based on the nuclear architecture of telomeres

“…Other predictors are PSA (prostate cancer) or EGFR (colon cancer). In recent years the focus has shifted toward molecular markers in genetics, epigenetics, the analysis of gene-expression patterns (22), and proteomics (23)(24)(25). The molecular cancer diagnostic is looking at changes on genetic and epigenetic levels (26), translocations (SKY), and variation in copy numbers (array CGH).…”

Proteomics and the search for biomarkers of female reproductive diseases

“…Isotopic labelling was used to quantitate the presence of human-derived peptides, which could only have been produced by the implanted ovarian tumour. From 106 proteins of interest identified, 58 were secreted or shed from tumour cells; five of these were confirmed by independent means at increased levels in an independent set of plasma samples (Pitteri et al 2009). This is one of the most exciting studies in the field to date, and this demonstrates the power of quantitative proteomics for the identification of biomarkers of ovarian cancer.…”

“…In a more recent study, immunodepleted plasma from a mouse xenograft model was assessed for the presence of circulating human peptides (Pitteri et al 2009). Isotopic labelling was used to quantitate the presence of human-derived peptides, which could only have been produced by the implanted ovarian tumour.…”