Verification of Endometrial Tissue Biomarkers Previously Discovered Using Mass Spectrometry-Based Proteomics by Means of Immunohistochemistry in a Tissue Microarray Format

Abstract

Verification of candidate protein biomarkers is a necessary step in moving from the initial discovery to application. Here, we report results of a verification exercise involving six candidate endometrial cancer biomarkers previously discovered using mass-tagging and multidimensional liquid chromatography/tandem mass spectrometry (DeSouza L., et al. J. Proteome Res. 2005, 4, 377-386) on a cohort of 148 patient samples by means of immunohistochemistry on a tissue microarray format. A panel of the three best-performing biomarkers, chaperonin 10, pyruvate kinase M2, and alpha-1-antitrypsin, achieved a sensitivity of 0.85, specificity of 0.93, predictive value of 0.90, and positive predictive value of 0.88 in discriminating malignant from benign endometrium. The ruggedness of this panel of biomarkers was verified in a 2/3-training-set-1/3-test-set cross-validation analysis by randomly splitting the cohort in 10 ways. The roles of chaperonin 10 and pyruvate kinase M2 in tumorigenesis confirm them as credible cancer biomarkers.

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

“…18 AAT has been found to be associated with a number of cancers, including lymphoma and cancers of the liver, lung, stomach, bladder, gall-bladder, 54,55 and endometrium. [18][19][20] MIF has been found to be overexpressed in a number of cancers, including endometrial, 18 hepatocellular, 56 non-small-cell lung, 57 and brain. 58,59 In addition to the above, a number of proteins that have been linked to other cancers have also been identified in this study.…”

Identification of transgelin as a potential novel biomarker for gastric adenocarcinoma based on proteomics technology

“…This complicated interplay of factors leading to neoplastic progression is ultimately reXected in the protein expression proWles of cells. Thus, study of these proWles can reveal speciWc biomarkers for cancer (Roeßler et al 2005;Melle et al 2005;Xing et al 2006;Rosty et al 2002;Dube et al 2007). Biomarkers are the speciWc protein products of active genes, which represent the molecular characteristic or signature of cells (Aung et al 2006;Srinivas et al 2001).…”

Proteomics-Based Approach Identified Differentially Expressed Proteins With Potential Roles in Endometrial Carcinoma

“…To date, only a few proteomic studies on EC have been reported; however, some of the findings seem to be noteworthy and have been verified by immunohistochemical assays. 2,3 These studies reported slightly different findings and conclusions, which might be due to ethnic differences among patients or technical problems such as varying ability of mass spectrometry (MS) identification.…”