IPO-38 is identified as a novel serum biomarker of gastric cancer based on clinical proteomics technology.
ABSTRACT Gastric cancer is one of the most common malignancies in China. So far, there are few reliable serum biomarkers for diagnosis. The available biomarkers of CEA, CA19-9 and CA72-4 are not sufficiently sensitive and specific for gastric cancer. In this study, a high density antibody microarray was used for identifying new biomarkers from serum samples of gastric cancer. Serum samples from colorectal cancer, pancreatic cancer, hepatocellular cancer, and breast cancer were also screened for comparative study. As result, some candidate biomarkers were identified. IPO-38, an up-regulated serum protein in gastric cancer was selected for subsequent validation including serum IPO-38 expression by ELISA and IPO-38 protein expression by immunohistochemistry. The immunoprecipitation by IPO-38 for gastric cancer cell line and MALDI-TOF/TOF mass spectrometer suggested that pull-down of IPO-38 belongs to H2B histone, which was supported by co-localization study of laser scanning confocal microscope. A follow-up study showed that the survival rate of IPO-38 negative group was better than that in IPO-38 positive group. The study first clarified the property of IPO-38 proliferating marker, and proposed that IPO-38 protein is a promising biomarker both for diagnosis and for predicting prognosis of gastric cancer.
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ABSTRACT: The IRX1 tumor suppressor gene is located on 5p15.33, a cancer susceptibility locus. Loss of heterozygosity of 5p15.33 in gastric cancer was identified in our previous work. In this study, we analyzed the molecular features and function of IRX1. We found that IRX1 expression was lost or reduced in gastric cancer. However, no mutations were identified in IRX1-encoding regions. IRX1 transcription was suppressed by hypermethylation, and the expression of IRX1 mRNA was partially restored in gastric cancer cells after 5-Aza-dC treatment. Restoring IRX1 expression in SGC-7901 and NCI-N87 gastric cancer cells inhibited growth, invasion and tumorigenesis in vitro and in vivo. We identified a number of target genes by global microarray analysis after IRX1 transfection combined with real-time PCR and chromatin immunoprecipitation assay. BDKRB2, an angiogenesis-related gene, HIST2H2BE and FGF7, cell proliferation and invasion-related genes, were identified as direct IRX1 target genes. The hypermethylation of IRX1 was not only detected in primary gastric cancer tissues but also in the peripheral blood of gastric cancer patients, suggesting IRX1 could potentially serve as a biomarker for gastric cancer.Oncogene 05/2010; 29(27):3908-20. · 8.56 Impact Factor
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ABSTRACT: Gastric cancer is the second most common cause of cancer deaths worldwide and due to its poor prognosis, it is important that specific biomarkers are identified to enable its early detection. Through 2-D gel electrophoresis and MALDI-TOF-TOF-based proteomics approaches, we found that 14-3-3β, which was one of the proteins that were differentially expressed by 5-fluorouracil-treated gastric cancer SC-M1 cells, was upregulated in gastric cancer cells. 14-3-3β levels in tissues and serum were further validated in gastric cancer patients and controls. The results showed that 14-3-3β levels were elevated in tumor tissues (n=40) in comparison to normal tissues (n=40; p<0.01), and serum 14-3-3β levels in cancer patients (n=145) were also significantly higher than those in controls (n=63; p<0.0001). Elevated serum 14-3-3β levels highly correlated with the number of lymph node metastases, tumor size and a reduced survival rate. Moreover, overexpression of 14-3-3β enhanced the growth, invasiveness and migratory activities of tumor cells. Twenty-eight proteins involved in anti-apoptosis and tumor progression were also found to be differentially expressed in 14-3-3β-overexpressing gastric cancer cells. Overall, these results highlight the significance of 14-3-3β in gastric cancer cell progression and suggest that it has the potential to be used as a diagnostic and prognostic biomarker in gastric cancer.Proteomics 06/2011; 11(12):2423-39. · 4.43 Impact Factor
- American Journal of Cancer Science. 01/2013;