Evaluation of Serum Amyloid A as a Biomarker for Gastric Cancer

BackgroundSerum amyloid A (SAA) is a useful biomarker for gastric cancer in an animal model. We investigated the potential of SAA as a biomarker for gastric cancer in humans.MethodsSerum levels of SAA from 96 gastric cancer patients were measured before and after curative gastrectomy; 32 patients with gastric ulcers and 52 healthy subjects were the control groups. The immunohistochemical study was performed to evaluate the protein expression over gastric cancer tissue slides.ResultsThe mean SAA concentration was higher in gastric cancer patients (88.54 ± 50.44 mg/l) than in healthy subjects (3.36 ± 2.29 mg/l) and gastric ulcer patients (10.48 ± 8.97 mg/l) (P < .05). The SAA concentration was associated with tumor stage (P = .0244) and location (P = .0016) but not with Lauren’s histological type (P = .839). In the multivariate analysis, SAA level was correlated with tumor location (P < .0001) and lymph node status (P < .05). During follow-up, the mean SAA concentration increased significantly in 24 patients with tumor recurrence (P < .05) but did not change in 77 patients without recurrence. In the survival analysis, patients with SAA levels > 97 mg/l had a nearly fourfold increase in risk of death. Immunoreactivity was most prominent in blood vessel regions but not within cancer cells.ConclusionsThese data not only demonstrated SAA was useful in predicting survival of patients with gastric cancer, but they also showed that SAA was a valuable tool for postoperative follow-up.

[1]  G. Friedman,et al.  Helicobacter pylori infection and the risk of gastric carcinoma. , 1991, The New England journal of medicine.

[2]  E. Martinelli,et al.  Interleukin-6 serum level correlates with survival in advanced gastrointestinal cancer patients but is not an independent prognostic indicator. , 2001, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[3]  K. Hioki,et al.  Correlation of preoperative carcinoembryonic antigen levels and prognosis of gastric cancer patients , 1994, Cancer.

[4]  M. Cormican,et al.  The acute phase response in breast carcinoma. , 2002, Anticancer research.

[5]  Alter Mj,et al.  Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation. , 1991, BMJ.

[6]  H. Sasano,et al.  Interleukin 6-producing gastric carcinoma with fever, hypergammaglobulinemia, and plasmacytosis in bone marrow. , 1994, Gastroenterology.

[7]  M. Pras,et al.  Serum amyloid A (SAA) variations in patients with cancer: correlation with disease activity, stage, primary site, and prognosis. , 1986, Journal of clinical pathology.

[8]  R. Hamazoe,et al.  Carcinoembryonic antigen in gastric cancer patients. , 1987, Oncology.

[9]  J. Söltoft Immunoglobulin-containing cells in normal jejunal mucosa and in ulcerative colitis and regional enteritis. , 1969, Scandinavian journal of gastroenterology.

[10]  I. Glojnarić,et al.  Serum Amyloid A Protein (SAA) in Colorectal Carcinoma , 2001, Clinical chemistry and laboratory medicine.

[11]  F. Roviello,et al.  Prognostic Significance of CEA, CA 19-9 and CA 72-4 Preoperative Serum Levels in Gastric Carcinoma , 1999, Oncology.

[12]  K. Hagihara,et al.  IL-6 plays a critical role in the synergistic induction of human serum amyloid A (SAA) gene when stimulated with proinflammatory cytokines as analyzed with an SAA isoform real-time quantitative RT-PCR assay system. , 2004, Biochemical and biophysical research communications.

[13]  C. Chi,et al.  Serum interleukin-6 levels reflect disease status of gastric cancer. , 1996, The American journal of gastroenterology.

[14]  J. Kaneti,et al.  Importance of serum amyloid A (SAA) level in monitoring disease activity and response to therapy in patients with prostate cancer , 2004, Urological Research.

[15]  P. Laurén,et al.  THE TWO HISTOLOGICAL MAIN TYPES OF GASTRIC CARCINOMA: DIFFUSE AND SO-CALLED INTESTINAL-TYPE CARCINOMA. AN ATTEMPT AT A HISTO-CLINICAL CLASSIFICATION. , 1965, Acta pathologica et microbiologica Scandinavica.

[16]  M. Kuo,et al.  IL-6 inhibits apoptosis and retains oxidative DNA lesions in human gastric cancer AGS cells through up-regulation of anti-apoptotic gene mcl-1. , 2001, Carcinogenesis.

[17]  W. Lee,et al.  Epstein-Barr virus LMP1 modulates the malignant potential of gastric carcinoma cells involving apoptosis. , 1998, The American journal of pathology.

[18]  Y. Tomita,et al.  Significance of serum amyloid a on the prognosis in patients with renal cell carcinoma , 2001, Cancer.

[19]  G. De Backer,et al.  Discriminative value of serum amyloid A and other acute-phase proteins for coronary heart disease. , 2002, Atherosclerosis.

[20]  T. Yamada,et al.  Serum Amyloid A (SAA): a Concise Review of Biology, Assay Methods and Clinical Usefulness , 1999, Clinical chemistry and laboratory medicine.

[21]  S. Vollset,et al.  Helicobacter pylori infection and risk of cardia cancer and non-cardia gastric cancer. A nested case-control study. , 1999, Scandinavian journal of gastroenterology.

[22]  D. Chan,et al.  Identification of tumor‐associated plasma biomarkers using proteomic techniques: From mouse to human , 2004, Proteomics.

[23]  C. Stadtländer,et al.  Molecular epidemiology, pathogenesis and prevention of gastric cancer. , 1999, Carcinogenesis.

[24]  F. Safi,et al.  Comparison of CA 72-4, CA 19-9 and CEA in the diagnosis and monitoring of gastric cancer , 1995, The International journal of biological markers.

[25]  H. Egami,et al.  Comparative effectiveness of the tumour diagnostics, CA 19-9, CA 125 and carcinoembryonic antigen in patients with diseases of the digestive system. , 1987, Gut.

[26]  G. Daar,et al.  Serum levels of interleukin-1, interleukin-6 and tumour necrosis factor-alpha in patients with gastric carcinoma. , 1995, Cancer letters.

[27]  T. Yip,et al.  Identification of Serum Amyloid A Protein As a Potentially Useful Biomarker to Monitor Relapse of Nasopharyngeal Cancer by Serum Proteomic Profiling , 2004, Clinical Cancer Research.

[28]  G. M. D'eril,et al.  Biological variation of serum amyloid A in healthy subjects. , 2001, Clinical chemistry.

[29]  K. Inokuchi,et al.  The clinical usefulness of preoperative CEA determination in gastric cancer , 1987, The Japanese journal of surgery.

[30]  C. Cho,et al.  Regulation of interleukin 6 production in a human gastric epithelial cell line MKN-28. , 2000, Cytokine.

[31]  L. Sullivan,et al.  Serum amyloid A to monitor cancer dissemination. , 1979, Annals of internal medicine.

[32]  J. Mabrut,et al.  Skeletonizing en-bloc gastrectomy for adenocarcinoma in Caucasian patients , 2003, Gastric Cancer.

[33]  D. Graham,et al.  Relation between Cytokines and Helicobacter pylori in Gastric Cancer , 2001, Helicobacter.

[34]  Hsueh-Fen Juan,et al.  Biomic study of human myeloid leukemia cells differentiation to macrophages using DNA array, proteomic, and bioinformatic analytical methods , 2002, Electrophoresis.

[35]  G. Catalano,et al.  Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome. , 2002, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.