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Discovery of SLC3A2 cell membrane protein as a potential gastric cancer biomarker: implications in molecular imaging.

ABSTRACT: Despite decreasing incidence and mortality, gastric cancer remains the second leading cause of cancer-related deaths in the world. Successful management of gastric cancer is hampered by lack of highly sensitive and specific biomarkers especially for early cancer detection. Cell surface proteins that are aberrantly expressed between normal and cancer cells are potentially useful for cancer imaging and therapy due to easy accessibility of these targets. Combining two-phase partition and isobaric tags for relative and absolute quantification methods, we compared the relative expression levels of membrane proteins between noncancer and gastric cancer cells. About 33% of the data set was found to be plasma membrane and associated proteins using this approach (compared to only 11% in whole cell analysis), several of which have never been previously implicated in gastric cancer. Upregulation of SLC3A2 in gastric cancer cells was validated by immunoblotting of a panel of 13 gastric cancer cell lines and immunohistochemistry on tissue microarrays comprising 85 matched pairs of normal and tumor tissues. Immunofluorescence and immunohistochemistry both confirmed the plasma membrane localization of SLC3A2 in gastric cancer cells. The data supported the notion that SLC3A2 is a potential biomarker that could be exploited for molecular imaging-based detection of gastric cancer.

SUBMITTER: Yang Y

PROVIDER: S-EPMC3749780 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Discovery of SLC3A2 cell membrane protein as a potential gastric cancer biomarker: implications in molecular imaging.

Yang Yixuan Y Toy Weiyi W Choong Lee Yee LY Hou Peiling P Ashktorab Hassan H Smoot Duane T DT Yeoh Khay Guan KG Lim Yoon Pin YP

Journal of proteome research 20121126 12

Despite decreasing incidence and mortality, gastric cancer remains the second leading cause of cancer-related deaths in the world. Successful management of gastric cancer is hampered by lack of highly sensitive and specific biomarkers especially for early cancer detection. Cell surface proteins that are aberrantly expressed between normal and cancer cells are potentially useful for cancer imaging and therapy due to easy accessibility of these targets. Combining two-phase partition and isobaric t ...[more]

PMID: 23116296

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Project description:BackgroundComplex molecular events lead to development and progression of liver cirrhosis to HCC. Differentially expressed nuclear membrane associated proteins are responsible for the functional and structural alteration during the progression from cirrhosis to carcinoma. Although alterations/ post translational modifications in protein expression have been extensively quantified, complementary analysis of nuclear membrane proteome changes have been limited. Deciphering the molecular mechanism that differentiate between normal and disease state may lead to identification of biomarkers for carcinoma.ResultsMany proteins displayed differential expression when nuclear membrane proteome of hepatocellular carcinoma (HCC), fibrotic liver, and HepG2 cell line were assessed using 2-DE and ESI-Q-TOF MS/MS. From the down regulated set in HCC, we have identified for the first time a 15 KDa cytochrome b5A (CYB5A), ATP synthase subunit delta (ATPD) and Hemoglobin subunit beta (HBB) with 11, 5 and 22 peptide matches respectively. Furthermore, nitrosylation studies with S-nitrosocysteine followed by immunoblotting with anti SNO-cysteine demonstrated a novel and biologically relevant post translational modification of thiols of CYB5A in HCC specimens only. Immunofluorescence images demonstrated increased protein S-nitrosylation signals in the tumor cells and fibrotic region of HCC tissues. The two other nuclear membrane proteins which were only found to be nitrosylated in case of HCC were up regulated ATP synthase subunit beta (ATPB) and down regulated HBB. The decrease in expression of CYB5A in HCC suggests their possible role in disease progression. Further insight of the functional association of the identified proteins was obtained through KEGG/ REACTOME pathway analysis databases. String 8.3 interaction network shows strong interactions with proteins at high confidence score, which is helpful in characterization of functional abnormalities that may be a causative factor of liver pathology.ConclusionThese findings may have broader implications for understanding the mechanism of development of carcinoma. However, large scale studies will be required for further verification of their critical role in development and progression of HCC.

Dataset Information

Discovery of SLC3A2 cell membrane protein as a potential gastric cancer biomarker: implications in molecular imaging.

Publications

Discovery of SLC3A2 cell membrane protein as a potential gastric cancer biomarker: implications in molecular imaging.

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