IPO-38 is identified as a novel serum biomarker of gastric cancer based on clinical proteomics technology

Department of Surgery of Ruijin Hospital, Shanghai Institute of Digestive Surgery, Shanghai Jiaotong University, 197 Ruijin second Road, Shanghai, 200025, P.R. China.
Journal of Proteome Research (Impact Factor: 5). 10/2008; 7(9):3668-77. DOI: 10.1021/pr700638k
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: To identify potential biomarkers of primary gallbladder cancer (PGC). Fresh PGC, cholecystitis and normal gallbladder tissue specimens collected from 10 patients, respectively, were subjected to comparative proteomic analysis. The proteomic patterns of PGC were compared with those of cholecystitis and normal gallbladder tissues using two-dimensional gel electrophoresis (2-DE). The differentially expressed proteins were then identified using a MALDI-TOF mass spectrometer (MS) and database searches. To further validate these proteins, 20 samples of PGC tissues and normal tumor-adjacent tissues were collected for Western blot, quantitative real-time PCR, and immunohistochemical staining assay. Seven differentially expressed protein spots were detected by 2-ED analysis by comparing the average maps of PGC, cholecystitis and normal gallbladder tissues. Six of the seven differentially expressed proteins were identified using MALDI-TOF MS, with three overexpressed and three underexpressed in PGC tissue. Protein levels of annexin A4 (ANXA4) were significantly elevated, and heat shock protein 90-beta (Hsp90β) and dynein cytoplasmic 1 heavy chain 1 (Dync1h1) were decreased in PGC tissues relative to the normal tumor-adjacent tissues as shown by Western blot analysis. However, levels of actin, aortic smooth muscle and gamma-actin were unchanged. In addition, the mRNA levels of all 5 proteins showed similar changes to those of the protein levels (P < 0.01). Further validation by immunohistochemical analysis showed the upregulated expression of ANXA4 and decreased expression of Hsp90β and Dync1h1 in the cytoplasm of PGC tissues relative to the normal tumor-adjacent tissues. Three proteins are identified as potential biomarkers of PGC using proteomic analysis. The functions of these proteins in the carcinogenesis of PGC remain to be studied.
    World Journal of Gastroenterology 05/2014; 20(18):5511-8. DOI:10.3748/wjg.v20.i18.5511 · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cancer has been always in a great attention in the field of molecular biology. By applying large-scale tools such as advanced proteomics, cancer diagnosis and treatment have been improved greatly since. Cancers of esophagus, gastric, and colon accounted for major health problem globally. Biomarker panel could bring out the accuracy for cancer evaluation tests as it can suggest a group of candidate molecules specified to particular malignancy in a way that distinguishing malignant tumors from benign, differentiating from other diseases, and identifying each stages with high specificity and sensitivity. In this review, a systematic search of unique protein markers reported by several proteomic literatures are classified in their specific cancer type group as novel panels for feasible accurate malignancy diagnosis and treatment. About thousands of proteins were studied; however, a little number of them was belonged to a specific kind of malignancy. In conclusion, despite the fact that combinatorial biomarkers appear to be hopeful, more evaluation of them is crucial to achieve the most relevant risk markers panel to the disease to provide precise clinical test
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phosphatase of regenerating liver-3 (PRL-3) is believed to be associated with cell motility, invasion, and metastasis. Our previous work found that PRL-3 is highly overexpressed in gastric cancer (GC) tissue with peritoneal metastasis and directly involved in the pathogenesis of GC peritoneal metastasis. Moreover, we further found that the down-regulation of endogenous miR-495 expression plays a causative role in over expression of PRL-3 in GC peritoneal metastasis. However, the molecular regulation mechanisms by which endogenous miR-495 expression is down-regulated and PRL-3 promotes GC peritoneal metastasis remain to be clearly elucidated. Some studies have shown that the promoter methylation is closely related to the miRNA gene expression. Therefore, in present study, based on our previous findings, we will analysis whether DNA methylation is a major cause of the down-expression of endogenous miR-495, which results in PRL-3 overexpression in GC peritoneal metastasis. Methylation specific PCR (MSP) and sodium bisulfite sequencing method (BSP) detected miR-495 gene promoter methylation status. We treated GC cell lines with 5-Aza-2'-deoxycytidine (5-Aza-dC) to make the gene promoter methylation inactivation. By treating with 5-Aza-dC the migration and invasion of GC cells were significantly inhibited. And the miR-495 was overexpressing, corresponds to the mRNA and protein levels of PRL-3 were reduced, the ability of invasion and metastasis was inhibited. This study suggest that miR-495 have tumor suppressor properties and are partially silenced by DNA hypermethylation in GC, will provide new strategies for prevention and treatment of GC peritoneal metastasis. Copyright © 2014. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 12/2014; 456(1). DOI:10.1016/j.bbrc.2014.11.083 · 2.28 Impact Factor