Research Article| Volume 42, ISSUE 12, P1897-1903, August 2006

Prediction of peritoneal metastasis in advanced gastric cancer by gene expression profiling of the primary site


      Peritoneal metastasis is the most common cause of tumour progression in advanced gastric cancer. Clinicopathological findings including cytologic examination of peritoneal lavage have been applied to assess the risk of peritoneal metastasis, but are sometimes inadequate for predicting peritoneal metastasis in individuals. Hence, we tried to construct a new prediction system for peritoneal metastasis by using a PCR-based high throughput array with 2304 genes. The prediction system, constructed from the learning set comprised of 30 patients with the most informative 18 genes, classified each case into a ‘good signature group’ or ‘poor signature group’. Then, we confirmed the predictive performance in an additional validation set comprised of 24 patients, and the prediction accuracy for peritoneal metastasis was 75%. Kaplan–Meier analysis with peritoneal metastasis revealed significant difference between these two groups (P = 0.0225). By combining our system with conventional clinicopathological factors, we can identify high risk cases for peritoneal metastasis more accurately.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Parkin D.M.
        • Piasani P.
        • Ferlay J.
        Estimates of the worldwide incidence of 25 major cancers in 1990.
        Int J Cancer. 1999; 80: 827-841
        • Benevolo M.
        • Mottolese M.
        • Cosimelli M.
        • et al.
        Diagnostic and prognostic value of peritoneal immunocytology in gastric cancer.
        J Clin Oncol. 1998; 16: 3406-3411
        • Yoo C.H.
        • Noh S.H.
        • Shin D.W.
        • Choi S.H.
        • Min J.S.
        Recurrence following curative resection for gastric carcinoma.
        Br J Surg. 2000; 87: 236-242
        • Yokozaki H.
        • Yasui W.
        • Tahara E.
        Genetic and epigenetic changes in stomach cancer.
        Int Rev Cytol. 2001; 204: 49-95
        • Ponder B.A.J.
        Cancer genetics.
        Nature. 2001; 411: 336-341
        • Taniguchi K.
        • Yonemura Y.
        • Nojima N.
        • et al.
        The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor.
        Cancer. 1998; 82: 2112-2122
        • van ’t Veer L.J.
        • Dai H.
        • van de Vijver M.J.
        • et al.
        Gene expression profiling predicts clinical outcome of breast cancer.
        Nature. 2002; 415: 530-536
        • Beer D.G.
        • Kardia S.L.
        • Huang C.C.
        • et al.
        Gene-expression profiles predict survival of patients with lung adenocarcinoma.
        Nature Med. 2002; 8: 816-824
        • Wang Y.
        • Jatkoe T.
        • Zhang Y.
        • et al.
        Gene expression profiles and molecular markers to predict recurrence of Dukes’ B colon cancer.
        J Clin Oncol. 2004; 22: 1564-1571
        • Kato K.
        Adaptor-tagged competitive PCR: a novel method for measuring relative gene expression.
        Nucleic Acids Res. 1997; 25: 4694-4696
        • Motoori M.
        • Takemasa I.
        • Yano M.
        • et al.
        Prediction of recurrence in advanced gastric cancer patients after curative resection by gene expression profiling.
        Int J Cancer. 2005; 114: 963-968
        • Muro S.
        • Takemasa I.
        • Oba S.
        • et al.
        Identification of expressed genes linked to malignancy of human colorectal carcinoma by parametric clustering of quantitative expression data.
        Genome Biol. 2003; 4: R21
        • Kurokawa Y.
        • Matoba R.
        • Takemasa I.
        • et al.
        Molecular-based prediction of early recurrence in hepatocellular carcinoma.
        J Hepatol. 2004; 41: 284-291
        • Iwao-Koizumi K.
        • Matoba R.
        • Ueno N.
        • et al.
        Prediction of docetaxel response in human breast cancer by gene expression profiling.
        J Clin Oncol. 2005; 23: 422-431
        • Japanese Gastric Cancer Association
        Japanese classification of gastric carcinoma.
        Gastric Cancer. 1998; 1: 10-24
        • Matoba R.
        • Kato K.
        • Saito S.
        • et al.
        Gene expression in mouse cerebellum during its development.
        Gene. 2000; 241: 125-131
        • Oba S.
        • Sato M.
        • Takemasa I.
        A Bayesian missing value estimation method for gene expression profile data.
        Bioinformatics. 2003; 19: 2088-2096
        • Golub T.R.
        • Slonim D.K.
        • Tamayo P.
        • et al.
        Molecular classification of cancer: class discovery and class prediction by gene expression monitoring.
        Science. 1999; 286: 531-537
        • Abe S.
        • Yoshimura H.
        • Tabara H.
        • et al.
        Curative resection of gastric cancer: limitation of peritoneal lavage cytology in predicting the outcome.
        J Surg Oncol. 1995; 59: 226-229
        • Adachi Y.
        • Oshiro T.
        • Mori M.
        • Maehara Y.
        • Sugimachi K.
        Prediction of early and late recurrence after curative resection for gastric carcinoma.
        Cancer. 1996; 77: 2445-2448
        • Kodera Y.
        • Nakanishi H.
        • Ito S.
        • et al.
        Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time reverse transcriptase-polymerase chain reaction.
        Ann Surg. 2002; 4: 499-506
        • Sakakura C.
        • Hagiwara A.
        • Nakanishi M.
        • et al.
        Differential gene expression profiles of gastric cancer cells established from primary tumour and malignant ascites.
        Br J Cancer. 2002; 87: 1153-1161
        • Mori K.
        • Aoyagi K.
        • Ueda T.
        • et al.
        Highly specific marker genes for detecting minimal gastric cancer cells in cytology negative peritoneal washings.
        Biochem Biophys Res Commun. 2004; 313: 931-937
        • Tanaka T.
        • Kumagai K.
        • Shimizu K.
        • Masuo K.
        • Yamagata K.
        Peritoneal metastasis in gastric cancer with particular reference to lymphatic advancement; extra nodal invasion is a significant risk factor for peritoneal metastasis.
        J Surg Oncol. 2000; 75: 165-171
        • Maehara Y.
        • Tomisaki S.
        • Oda S.
        • et al.
        Lymphatic advancement to peritoneal dissemination and liver metastasis in gastric cancer patients.
        Anticancer Res. 1994; 14: 2755-2757
        • Ramaswamy S.
        • Ross K.N.
        • Lander E.S.
        • Golub T.R.
        A molecular signature of metastasis in primary solid tumors.
        Nat Genet. 2003; 33: 49-54
        • Wong B.C.
        • Wang W.P.
        • Cho C.H.
        • et al.
        12-Lipoxygenase inhibition induced apoptosis in human gastric cancer cells.
        Carcinogenesis. 2001; 22: 1349-1354
      1. Isomoto H, Oka M, Yano Y, et al. Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer. Cancer Lett 198:219–28.

        • Kristiansen G.
        • Schluns K.
        • Yongwei Y.
        • et al.
        CD24 is an independent prognostic marker of survival in nonsmall cell lung cancer patients.
        Br J Cancer. 2003; 88: 231-236
        • Earle C.C.
        • Maroun J.A.
        Adjuvant chemotherapy after curative resection for gastric cancer in non-Asian patients: Revisiting a meta-analysis of randomized trials.
        Eur J Cancer. 1999; 35: 1059-1064