Protein Expression Profiling of Endometrial Malignancies Reveals a New Tumor Marker:  Chaperonin 10

Abstract

Endometrial carcinoma is a common malignancy in women, being exceeded in incidence only by that of breast, lung, and colorectal cancers. At present, no serum tumor markers are available for the monitoring of endometrial carcinoma patients, and patients with recurrent disease are detected only following the development of symptoms or abnormalities in imaging assessments. Similarly, no screening tools are available for endometrial carcinoma. Protein profiling by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) has proven to be a sensitive and fast method of analysis for small proteins or peptides to yield specific biomarkers. In this study, a variety of normal and malignant endometrial tissue samples were fractionated and analyzed by SELDI-TOF MS (SELDI is a version of MALDI utilizing protein "chips"). A number of proteins displayed differential expression in malignant endometrial tissues. One of the prominent proteins fractionated by weak cation exchange chromatography and displaying enhanced expression in these malignant tissues was identified as chaperonin 10. The increased expression of chaperonin 10 in malignant endometrial tissues was further confirmed by parallel Western blot and immunohistochemistry analyses.

Endometrial Carcinoma Biomarker Discovery and Verification Using Differentially Tagged Clinical Samples with Multidimensional Liquid Chromatography and Tandem Mass Spectrometry

“…Cpn 10, calgizzarin, transgelin, and MIF are all proteins we had detected previously as being differentially expressed in EmCa samples; these have all also been implicated in various other forms of cancer and were discussed previously (3,50). Macrophage capping protein (Cap-G) and leucine aminopeptidase 3 (LAP3) were not identified in a sufficient number of EmCa samples to justify inclusion in the list of differentially expression proteins in this study.…”

Mass spectrometry of peptides and proteins from human blood

“…Immunological measurements, enzyme activities and other evidence indicate that blood proteins discovered by mass spectrometry have biological relevance (Marshall et al, 2003;Yang et al, 2004;Zhang et al, 2004;Malik et al, 2005;Gao et al, 2005a,b;Yokoi et al, 2005;Ogata et al, 2006;Haqqani et al, 2007;Plavina et al, 2007;Sardana, Marshall, & Diamandis, 2007;Qian et al, 2008a). The application of mass spectrometry to study blood proteins and peptides is increasing in importance and has detected many proteins not previously known to exist in blood Schenk et al, 2008).…”

Identification of Candidate Biomarker Proteins Released by Human Endometrial and Cervical Cancer Cells Using Two-Dimensional Liquid Chromatography/Tandem Mass Spectrometry

“…40,41 Our analyses show that extracellular chaperonin 10 carries two post-translational modifications at the N-terminus. 35,42 Extracellular chaperonin 10 probably functions as an immunosuppressant 41 and a growth factor 43 in neoplastic cell proliferation. PK-M2 is expressed selectively in metastatic cells, [44][45][46][47] primarily in its dimeric form.…”