Serum levels of an isoform of Apolipoprotein-AII as a potential marker for prostate cancer

Department of Microbiology and Molecular Cell Biology, Virginia Prostate Center, Eastern Virginia Medical School, 700 West Olney Road, Norfolk, VA 23501, USA.
Clinical Cancer Research (Impact Factor: 8.19). 03/2005; 11(3):1073-85.
Source: PubMed

ABSTRACT We recently showed that protein expression profiling of serum using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) has potential as a diagnostic approach for detection of prostate cancer. As a parallel effort, we have been pursuing the identification of the protein(s) comprising the individual discriminatory "peaks" and evaluating their utility as potential biomarkers for prostate disease.
We employed liquid chromatography, gel electrophoresis and tandem mass spectroscopy to isolate and identify a protein that correlates with observed SELDI-TOF MS mass/charge (m/z) values. Immunodepletion, immunoassay, and Western analysis were used to verify that the identified protein generated the observed SELDI peak. Subsequent immunohistochemistry was used to examine the expression of the proteins in prostate tumors.
An 8,946 m/z SELDI-TOF MS peak was found to retain discriminatory value in each of two separate data sets with an increased expression in the diseased state. Sequence identification by liquid chromatography-MS/MS and subsequent immunoassays verified that an isoform of apolipoprotein A-II (ApoA-II) is the observed 8,946 m/z SELDI peak. Immunohistochemistry revealed that ApoA-II is overexpressed in prostate tumors. SELDI-based immunoassay revealed that an 8.9-kDa isoform of ApoA-II is specifically overexpressed in serum from individuals with prostate cancer. ApoA-II was also overexpressed in the serum of individuals with prostate cancer who have normal prostate-specific antigen (0-4.0 ng/mL).
We have identified an isoform of ApoA-II giving rise to an 8.9K m/z SELDI "peak" that is specifically overexpressed in prostate disease. The ability of ApoA-II to detect disease in patients with normal prostate-specific antigen suggests potential utility of the marker in identifying indolent disease.

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    • "In addition, the abnormal expression of liver enrichment genes in tissues other than liver may be an important disease phenotype signature. For instance, apoA-II has been shown to be over-expressed in the serum of individuals with prostate cancer [20]. Under normal conditions the expression of this gene is low in all tissues except liver and spleen. "
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    • "It is simple, rapid, high-throughput, and needs small amount of samples, and particularly, it can capture proteins of small molecular weight and low abundance more effectively (Issaq et al., 2002). It has been extensively applied to the researches about tumor markers (Conrad et al., 2004; Petricoin and Liotta, 2004), such as prostate cancer (Walsh, 2003; Malik et al., 2005), breast carcinoma (Zeidan and Townsend, 2008), bladder cancer (Langbein et al., 2006), hepatocellular carcinoma (Paradis et al., 2005), nasopharyngeal cancer (Cho et al., 2004) and so on (Kozak et al., 2003). The relative molecular weight of the representative specific proteins (m/z 5907, 11673, 867 and 13725) found in patients with gastric cancer in our experiment; using SELDI technology, is all small. "
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