Serum levels of an isoform of Apolipoprotein-AII as a potential marker for prostate cancer
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.
- SourceAvailable from: Yao Yu
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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 . Under normal conditions the expression of this gene is low in all tissues except liver and spleen. "
ABSTRACT: The human liver plays a vital role in meeting the body's metabolic needs and maintaining homeostasis. To address the molecular mechanisms of liver function, we integrated multiple gene expression datasets from microarray, MPSS, SAGE and EST platforms to generate a transcriptome atlas of the normal human liver. Our results show that 17396 genes are expressed in the human liver. 238 genes were identified as liver enrichment genes, involved in the functions of immune response and metabolic processes, from the MPSS and EST datasets. A comparative analysis of liver transcriptomes was performed in humans, mice and rats with microarray datasets shows that the expression profile of homologous genes remains significantly different between mouse/rat and human, suggesting a functional variance and regulation bias of genes expressed in the livers. The integrated liver transcriptome data should provide a valuable resource for the in-depth understanding of human liver biology and liver disease.Genomics 11/2010; 96(5):281-9. DOI:10.1016/j.ygeno.2010.08.003 · 2.79 Impact Factor
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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. "
ABSTRACT: ObjectiveTo study the serum protein fingerprint of patients with pancreatic cancer and to screen for protein molecules closely related to pancreatic cancer during the onset and progression of the disease using surface-enhanced laser desorption and ionization time of fight mass spectrometry (SELDI-TOF-MS). MethodsSerum samples from 20 pancreatic cancers, 20 healthy volunteers and 18 patients with other pancreatic diseases. WCX magnetic beans and PBSII-C protein chips reader (Ciphergen Biosystems Ins.) were used. The protein fingerprint expression of all the Serum samples and the resulting profiles between cancer and normal were analyzed with Biomarker Wizard system. ResultsA group of proteomic peaks were detected. Four differently expressed potential biomarkers were identified with the relative molecular weights of 5705 Da, 4935 Da, 5318 Da and 3243 Da. Among them, two proteins with m/z5705, 5318Da down-regulated, and two proteins with m/z 4935, 3243 Da were up-regulated in pancreatic cancers. ConclusionSELDI technology can be used to screen significant proteins of differential expression in the serum of pancreatic cancer patients. These different proteins could be specific biomarkers of the patients with pancreatic cancer in the serum and have the potential value of further investigation.Chinese Journal of Cancer Research 09/2008; 20(3):171-176. DOI:10.1007/S11670-008-0171-4 · 0.93 Impact Factor
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ABSTRACT: Serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) appears to be an important diagnostic tool for a whole range of diseases. Sensitivities and specificities obtained with this new technology often seem superior to those obtained with current biomarkers. However, reproducibility and standardization are still problematic. The present review gives an overview of the diagnostic value of protein profiles obtained with SELDI in studies on prostate and ovarian cancer. To identify aspects important for protein profiling, we compare and discuss differences in pre- and post-analytical conditions presented in the literature supplemented with some of our own data. Further progress in protein profiling as a diagnostic tool requires a more comprehensive description of technical details in all future studies.Clinical Chemistry and Laboratory Medicine 02/2005; 43(12):1281-90. DOI:10.1515/CCLM.2005.222 · 2.96 Impact Factor