Abstract
The prognostic value of immunosuppressive acidic protein (IAP), which is known to suppress various immune responses in cancer patients, was studied in a prospective randomized trial of advanced gastric cancer patients, designed to evaluate the effect of PSK, a kind of biological response modifier with protein-bound polysaccharides. Preoperative serum IAP levels were determined in 228 patients who received radical gastric resection and tests conducted in one laboratory by the single radial immunodiffusion (SRID) method. All patients were followed up for 24 months or more. There was an overall significant difference in disease-free survival time in favour of the PSK-treated group compared with the control group. Preoperative IAP values were strongly associated with disease-free survival time. The statistical analysis to define an appropriate cut-off level for IAP was performed using Cox's proportional hazards model. The most significant difference was observed at the threshold value of 580 μg/ml, the hazard ratio being 2.13 with a 95% confidence interval [1.17, 3.88] (P=0.013). Patients in the PSK-treated group with a preoperative IAP of lower than 580 μg/ml showed improved disease-free survival (P=0.029), however, no significant difference was seen between the two groups when the preoperative IAP exceeded the threshold level. From these results, 580 μg/ml is postulated to be the most appropriate threshold value for predicting the prognosis of advanced gastric cancer patients, and it is suggested that PSK would be most effective in patients whose preoperative IAP level is lower than the threshold level.
Similar content being viewed by others
References
Tamura K, Shibata Y, Matsuda Y, Ishida N (1981) Isolation and characterization of an immunosuppressive acidic protein from ascitic fluids of cancer patients. Cancer Res 41:3244–3252
Shibata Y, Tamura K, Ishida N (1983) In vivo analysis of the suppressive effects of immunosuppressive acidic protein, a type of alfa-1 acid glycoprotein, in connection with its high level in tumor-bearing mice. Cancer Res 43:2889–2896
Chandrasekaran EV, Davila M, Nixon D, Mendicino J (1984) Structures of the oligosaccharide chains of two forms of alfa-1 acid glycoprotein purified from liver metastasis of lung, colon and breast tumors. Cancer Res 44:1557–1567
Yamanaka N, Harabuchi Y, Himi T, Kataura A (1988) Immunosuppressive substance in the sera of head and neck cancer patients. Cancer 62:1293–1298
Sawada M, Okudaira Y, Matsui Y, Shimizu Y (1983) Immunosuppressive acidic protein in patients with ovarian cancer. Cancer 52:2081–2085
Sakita M, Torii T, Imaki S, Kasuga M, Tamai M, Suzuki G, Kano M, Fujita Y, Majima S (1984) Immunosuppressive activity of sera from gastric cancer patients. Jpn J Surg 14(2):127–134
Mancini G, Garbonara AO, Hermans JF (1965) Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2:235–254
Saji S, Yokoyama Y, Niwa H, Takao H, Kida H, Kawata R, Tanemura H, Sakata K (1986) Clinical studies on serum immunosuppressive acidic protein (IAP) and ferritin in gastric cancer patients: With special reference to preoperative value and influence of surgical stress. J Surg Oncol 33:215–222
Kohgo Y, Sakamaki S, Niitsu Y (1989) Nonspecific humoral immunosuppressive factors with special reference to immunosuppressive acidic protein (IAP) and immunosuppressive substance (IS). Biotherapy 3(2):469–477
Akiyama J, Kawamura T, Gotohda E, Yamada Y, Hosokawa M, Kodama T, Kobayashi H (1977) Immunochemotherapy of transplanted KMT-17 tumor in WKA Ra by combination of cyclophosphamide and immunostimulatory protein-bound polysaccharide isolated from Basidiomycetes. Cancer Res 37:3042–3045
Toge T, Yamaguchi Y, Kegoya Y, Baba N, Yanagawa E, Hattori T (1989) Blocking of lymphocyte surface binding sites for the soluble suppressor factor by protein-bound polysaccharide, PSK. Int J Immunopharmacol 11:9–12
Hermanek P, Sobin LH (eds) (1987) International Union Against Cancer: TNM classification of malignant tumors, 4th edn. Springer Tokyo, pp 43–46
Nakazato H, Koike A, Ichihashi H, Saji S, Danno M, Ogawa N (1989) An effect of adjuvant immunochemotherapy using Krestin and 5-FU on gastric cancer patients with radical surgery — A randomized controlled trial by the cooperative study group. Jpn J Cancer Chemother 16(8):2563–2576. (In Japanese)
Cox DR (1972) Regression models and life-tables. J R Stat Soc (B) 34:187–220
Kalbfleisch JD, Prentice RL (1980) The statistical analysis of failure time data. Wiley and Sons, New York
Miwa K, The Japanese Research Society for Gastric Cancer (1984) Evaluation of the TNM Classification of stomach cancer and proposal for its rational stage-grouping. Jpn J Clin Oncol 14(3):385–410
Young FW, Takane Y, Leeuw J (1978) The principal components of mixed measurement level multivariate data — An alternating least square method with optimal scaling features. Psychometrika 43:279–281
Beutler B, Cerami A (1986) Cachectin and tumor necrosis factors as two sides of the same biological coin. Nature 320:584–588
Toh H, Hayashida H, Kikuno R, Yasunaga T, Miyata T (1985) Sequence similarity between EGF receptor and α-1 acid glycoprotein. Nature 314:199–200
Schmidt K, Kaufmann H, Isemura S, Bauer F, Emura J, Motoyama T, Ishiguro M, Nanno S (1973) Structure of α-1 acid glycoprotein. The complete amino acid sequence, multiple amino acid substitutions, and homology with the immunoglobulins. Biochemistry 12:2711–2724
Chu C, Lai L TY, Pokala HP (1982) Value of plasma alfa-1 acid glycoprotein assay in the detection of human colorectal cancer — Comparison with carcinoembryonic antigen. JNCI 68:75–79
Yamashita K, Hayashi H, Mure K, Ishikawa M, Shimizu T (1986) Serum immunosuppressive substance in patients with gynecologic malignancies and in pregnant women. Cancer 57:69–74
Gahmberg CG, Andersson LC (1987) Leucocyte surface origin of human α-1 acid glycoprotein (Orosomucoid). J Exp Med 148(2):507–521
Aozasa K, Ueda T, Ayata M, Tsujimoto M, Fujita M, Yamamura T, Tsujimura T (1987) Immunohistochemical determination of immunosuppressive acid protein in reactive and neoplastic disease of macrophage. Cancer 60:2424–2427
Urushizaki I, Ishitani K, Nagai T, Gocho Y, Koyama R (1977) Immunosuppressive factors in serum of patients with gastric carcinoma. Gann 68:413–421
Kondo T, Sakamoto J, Ichihashi H, Kamei H (1981) Effect of alternating administration of PSK and Carbazilquinone in tumor-bearing mice. Gann 72:293–299
Yoshikumi C, Nomoto K, Matsunaga K, Fujii T, Takeya K (1975) Mouse strain difference in the expression of antitumor activity of PS-K. Gann 66:649–654
Nomoto K, Yoshikumi C, Matsunaga K, Fujii T, Takeya K (1975) Restoration of antibody-forming capacities by PS-K in tumor-bearing mice. Gann 66:365–374
Fujii M, Fujii T, Saito K, Takahashi N, Yoshikumi C, Kakuchi J, Kawai Y (1987) Tumor growth promoting activity of an immunosuppressive substance and its modulation by protein-bound polysaccharide PSK. Immunol Lett 1987; 15:347–351
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Sakamoto, J., Koike, A., Saji, S. et al. Preoperative serum immunosuppressive acidic protein (IAP) test for the prognosis of gastric cancer: A statistical study of the threshold level and evaluation of the effect of the biological response modifier PSK. Surg Today 22, 530–536 (1992). https://doi.org/10.1007/BF00308899
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00308899