Identification of Peptide Tumor Markers in a Tumor Graft Model in Immunodeficient Mice

Abstract

The medical demand for useful biomarkers is large and still increasing. This is especially true for cancer, because for this disease adequate diagnostic markers with high specificity and sensitivity are still lacking. Despite advances in imaging technologies for early detection of cancer, peptidomic multiplex techniques evolved in recent years will provide new opportunities for detection of low molecular weight (LMW) proteome biomarker (peptides) by mass spectrometry. Improvements in peptidomics research were made based on separation of peptides and/or proteins by their physico-chemical properties in combination with mass spectrometric detection, respectively identification, and sophisticated bioinformatic tools for data analysis. To evaluate the potential of serological tumor marker detection by differential peptide display (DPD) we analyzed plasma samples from a tumor graft model. After subcutaneous injection of HCT-116 cells in immunodeficient mice and their growth to a palpable tumor, plasma samples were analyzed by DPD. The comparison of obtained mass spectrometric data allows discovery of tumor specific peptides which fit well into the biological context of cancer pathogenesis and show a strong correlation to tumor growth. The identified peptides indicate events associated with hyper-proliferation and dedifferentiation of cells from an epithelial origin, which are typical characteristics of human carcinomas. We conclude that these findings are a "proof of principle" to detect differentially expressed, tumor-related peptides in plasma of tumor-bearing mice.

Increased Plasma Concentrations of Cytoskeletal and Ca2+-Binding Proteins and Their Peptides in Psoriasis Patients

“…(A), Thb4 concentrations in plasma of psoriasis patients and healthy controls as assessed by an ELISA specific for the N terminus of Thb4 (amino acid residues [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and by an ELISA developed in-house that is specific for full-length Thb4 (residues 1-43). (B), Relative concentrations of calgranulin A and calgranulin B (spectral counts) and concentrations of calprotectin (ELISA measurements).…”

“…In recent years, proteomic analysis has led to the identification of candidate biomarkers for a variety of physiological and pathologic conditions (5)(6)(7). In our study, we used a combination of 2 proteomic methods to analyze both the protein content and low molecular weight (LMW) 3 peptide content of plasma samples from psoriasis patients and healthy donors.…”

Use of proteomic methods in the analysis of human body fluids in Alzheimer research

“…Depending on the mass accuracy of the mass spectrometer being used, peptides and small proteins up to 10–20 kDa can often be recognized. Top‐down strategies have been exploited using CE‐MS , LC‐MS and SELDI‐TOF‐MS systems. Absolute identification of proteins is more difficult with top‐down approaches than with bottom‐up approaches ( m/z ratios are often reported rather than protein identifications).…”

Peptidomic analysis of breast cancer reveals a putative surrogate marker for estrogen receptor-negative carcinomas

“…In addition, peptides usually have higher permeability between tissue compartments and therefore the chance of detecting peptides apart from the tissue itself (eg in blood) is higher compared to proteins and nucleic acids. Data from previous studies 27 suggest that truncated forms of PTa are capable of migrating from cells into the peripheral blood compartment. Therefore, we are currently conducting studies to determine whether THYA is detectable at different levels in plasma of breast cancer patients in correlation to the ER state.…”