Skip to main content
Top
Published in: Cancer Immunology, Immunotherapy 11/2010

01-11-2010 | Original Article

Tumor expression of B7-H4 predicts poor survival of patients suffering from gastric cancer

Authors: Jingting Jiang, Yibei Zhu, Changping Wu, Yueping Shen, Wenxiang Wei, Lujun Chen, Xiao Zheng, Jing Sun, Binfeng Lu, Xueguang Zhang

Published in: Cancer Immunology, Immunotherapy | Issue 11/2010

Login to get access

Abstract

To establish the prognostic value of B7-H4 expression by tumor cells in gastric cancer patients, we evaluated the association of B7-H4 expression with clinicopathologic factors and overall survival of gastric cancer patients. A retrospective cohort study including 156 gastric cancer patients was performed in the present report. Immunohistochemical assay was used to evaluate the expression of B7-H4 in the surgical specimens of gastric cancer tissues. Multi-univariate COX model was then used to evaluate the association of B7-H4 expression with the patients’ survival and clinicopathological parameters. B7-H4 expression in the gastric cancer cells was observed in about 44.9% gastric cancer specimens. Univariate analysis demonstrated that there was no correlation between B7-H4 expression and sex, age, histological type, pathological grade or tumor size. In contrast, B7-H4 expression correlated positively with cancer invasiveness and lymph node metastasis. In addition, the median overall survival time of patients with lower B7-H4 expression was 13 months longer than that of patients with higher expression (χ2 = 12.38, P < 0.0001), and the median disease-free survival time of patients with lower B7-H4 expression was significantly longer than that of patients with higher expression (33 vs. 16 months, χ2 = 14.977, P < 0.0001). After adjustment for other confounding factors, the COX model analysis indicated that the death risk was significantly higher in patients with higher B7-H4 expression than those with lower expression (RR = 1.85, 95% CI = 1.15–2.96). The present study demonstrated that higher B7-H4 expression in cancer cells was associated with poor prognosis of gastric cancer patients. This is consistent with the idea that B7-H4 promotes cancer progression, likely via inhibition of anti-tumor immune responses.
Literature
1.
go back to reference Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ (2009) Gastric cancer. Lancet 374:477–490 (PubMed:19625077)CrossRefPubMed Hartgrink HH, Jansen EP, van Grieken NC, van de Velde CJ (2009) Gastric cancer. Lancet 374:477–490 (PubMed:19625077)CrossRefPubMed
2.
go back to reference Yeh JM, Kuntz KM, Ezzati M, Goldie SJ (2009) Exploring the cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer in China in anticipation of clinical trial results. Int J Cancer 124:157–166 (PubMed:18823009)CrossRefPubMed Yeh JM, Kuntz KM, Ezzati M, Goldie SJ (2009) Exploring the cost-effectiveness of Helicobacter pylori screening to prevent gastric cancer in China in anticipation of clinical trial results. Int J Cancer 124:157–166 (PubMed:18823009)CrossRefPubMed
3.
go back to reference Lee JH, Ryu KW, Kook MC, Lee JY, Kim CG, Choi IJ, Kim SK, Jang S, Park SR, Kim YW, Nam BH, Bae JM (2008) Feasibility of laparoscopic sentinel basin dissection for limited resection in early gastric cancer. J Surg Oncol 98:331–335 (PubMed:18646047)CrossRefPubMed Lee JH, Ryu KW, Kook MC, Lee JY, Kim CG, Choi IJ, Kim SK, Jang S, Park SR, Kim YW, Nam BH, Bae JM (2008) Feasibility of laparoscopic sentinel basin dissection for limited resection in early gastric cancer. J Surg Oncol 98:331–335 (PubMed:18646047)CrossRefPubMed
4.
go back to reference Valentini V, Cellini F, Minsky BD, Mattiucci GC, Balducci M, D’Agostino G, D’Angelo E, Dinapoli N, Nicolotti N, Valentini C, La Torre G (2009) Survival after radiotherapy in gastric cancer: systematic review and meta-analysis. Radiother Oncol 92:176–183 (PubMed:19586672)CrossRefPubMed Valentini V, Cellini F, Minsky BD, Mattiucci GC, Balducci M, D’Agostino G, D’Angelo E, Dinapoli N, Nicolotti N, Valentini C, La Torre G (2009) Survival after radiotherapy in gastric cancer: systematic review and meta-analysis. Radiother Oncol 92:176–183 (PubMed:19586672)CrossRefPubMed
5.
go back to reference Sun P, Xiang JB, Chen ZY (2009) Meta-analysis of adjuvant chemotherapy after radical surgery for advanced gastric cancer. Br J Surg 96:26–33 (PubMed:19016271)CrossRefPubMed Sun P, Xiang JB, Chen ZY (2009) Meta-analysis of adjuvant chemotherapy after radical surgery for advanced gastric cancer. Br J Surg 96:26–33 (PubMed:19016271)CrossRefPubMed
6.
go back to reference Jiang J, Xu N, Wu C, Deng H, Lu M, Li M, Xu B, Wu J, Wang R, Xu J, Nilsson-Ehle P (2006) Treatment of advanced gastric cancer by chemotherapy combined with autologous cytokine-induced killer cells. Anticancer Res 26:2237–2242 (PubMed:16821594)PubMed Jiang J, Xu N, Wu C, Deng H, Lu M, Li M, Xu B, Wu J, Wang R, Xu J, Nilsson-Ehle P (2006) Treatment of advanced gastric cancer by chemotherapy combined with autologous cytokine-induced killer cells. Anticancer Res 26:2237–2242 (PubMed:16821594)PubMed
7.
go back to reference Morabito A, Carillio G, Longo R (2009) Systemic treatment of gastric cancer. Crit Rev Oncol Hematol 70:216–234 (PubMed:18829344)CrossRefPubMed Morabito A, Carillio G, Longo R (2009) Systemic treatment of gastric cancer. Crit Rev Oncol Hematol 70:216–234 (PubMed:18829344)CrossRefPubMed
8.
go back to reference Varadhachary G, Ajani JA (2005) Gastric cancer. Clin Adv Hematol Oncol 3:118–124 (PubMed:16166979)PubMed Varadhachary G, Ajani JA (2005) Gastric cancer. Clin Adv Hematol Oncol 3:118–124 (PubMed:16166979)PubMed
9.
go back to reference Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8:467–477 (PubMed:18500231)CrossRefPubMed Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8:467–477 (PubMed:18500231)CrossRefPubMed
10.
go back to reference Aunoble B, Sanches R, Didier E, Bignon YJ (2000) Major oncogenes and tumor suppressor genes involved in epithelial ovarian cancer (review). Int J Oncol 16:567–576 (PubMed:10675491)PubMed Aunoble B, Sanches R, Didier E, Bignon YJ (2000) Major oncogenes and tumor suppressor genes involved in epithelial ovarian cancer (review). Int J Oncol 16:567–576 (PubMed:10675491)PubMed
11.
go back to reference Nicosia SV, Bai W, Cheng JQ, Coppola D, Kruk PA (2003) Oncogenic pathways implicated in ovarian epithelial cancer. Hematol Oncol Clin North Am 17:927–943 (PubMed:12959183)CrossRefPubMed Nicosia SV, Bai W, Cheng JQ, Coppola D, Kruk PA (2003) Oncogenic pathways implicated in ovarian epithelial cancer. Hematol Oncol Clin North Am 17:927–943 (PubMed:12959183)CrossRefPubMed
12.
go back to reference Carreno BM, Collins M (2003) BTLA: a new inhibitory receptor with a B7-like ligand. Trends Immunol 24:524–527 (PubMed:14552835)CrossRefPubMed Carreno BM, Collins M (2003) BTLA: a new inhibitory receptor with a B7-like ligand. Trends Immunol 24:524–527 (PubMed:14552835)CrossRefPubMed
13.
go back to reference Wang S, Chen L (2004) Co-signaling molecules of the B7-CD28 family in positive and negative regulation of T lymphocyte responses. Microbes Infect 6:759–766 (PubMed:15207823)CrossRefPubMed Wang S, Chen L (2004) Co-signaling molecules of the B7-CD28 family in positive and negative regulation of T lymphocyte responses. Microbes Infect 6:759–766 (PubMed:15207823)CrossRefPubMed
14.
go back to reference Tringler B, Zhuo S, Pilkington G, Torkko KC, Singh M, Lucia MS, Heinz DE, Papkoff J, Shroyer KR (2005) B7-H4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res 11:1842–1848 (PubMed:15756008)CrossRefPubMed Tringler B, Zhuo S, Pilkington G, Torkko KC, Singh M, Lucia MS, Heinz DE, Papkoff J, Shroyer KR (2005) B7-H4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res 11:1842–1848 (PubMed:15756008)CrossRefPubMed
15.
go back to reference Choi IH, Zhu G, Sica GL, Strome SE, Cheville JC, Lau JS, Zhu Y, Flies DB, Tamada K, Chen L (2003) Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol 171:4650–4654 (PubMed:14568939)PubMed Choi IH, Zhu G, Sica GL, Strome SE, Cheville JC, Lau JS, Zhu Y, Flies DB, Tamada K, Chen L (2003) Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol 171:4650–4654 (PubMed:14568939)PubMed
16.
go back to reference Sun Y, Wang Y, Zhao J, Gu M, Giscombe R, Lefvert AK, Wang X (2006) B7-H3 and B7-H4 expression in non-small cell lung cancer. Lung Cancer 53:143–151 (PubMed:16782226)CrossRefPubMed Sun Y, Wang Y, Zhao J, Gu M, Giscombe R, Lefvert AK, Wang X (2006) B7-H3 and B7-H4 expression in non-small cell lung cancer. Lung Cancer 53:143–151 (PubMed:16782226)CrossRefPubMed
17.
go back to reference Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P, Brumlik M, Cheng P, Curiel T, Myers L, Lackner A, Alvarez X, Ochoa A, Chen L, Zou W (2006) B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 203:871–881 (PubMed:16606666)CrossRefPubMed Kryczek I, Zou L, Rodriguez P, Zhu G, Wei S, Mottram P, Brumlik M, Cheng P, Curiel T, Myers L, Lackner A, Alvarez X, Ochoa A, Chen L, Zou W (2006) B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 203:871–881 (PubMed:16606666)CrossRefPubMed
18.
go back to reference Kryczek I, Wei S, Zhu G, Myers L, Mottram P, Cheng P, Chen L, Coukos G, Zou W (2007) Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res 67:8900–8905 (PubMed:17875732)CrossRefPubMed Kryczek I, Wei S, Zhu G, Myers L, Mottram P, Cheng P, Chen L, Coukos G, Zou W (2007) Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res 67:8900–8905 (PubMed:17875732)CrossRefPubMed
19.
go back to reference Xue Q, Luan XY, Gu YZ, Wu HY, Zhang GB, Yu GH, Zhu HT, Wang M, Dong W, Geng YJ, Zhang XG (2010) The negative co-signaling molecule B7-H4 is expressed by human bone marrow-derived mesenchymal stem cells and mediates its T-cell modulatory activity. Stem Cells Dev 19:27–38 (PubMed:19788399) Xue Q, Luan XY, Gu YZ, Wu HY, Zhang GB, Yu GH, Zhu HT, Wang M, Dong W, Geng YJ, Zhang XG (2010) The negative co-signaling molecule B7-H4 is expressed by human bone marrow-derived mesenchymal stem cells and mediates its T-cell modulatory activity. Stem Cells Dev 19:27–38 (PubMed:19788399)
20.
go back to reference Yuan CL, Xu JF, Tong J, Yang H, He FR, Gong Q, Xiong P, Duan L, Fang M, Tan Z, Xu Y, Chen YF, Zheng F, Gong FL (2009) B7-H4 transfection prolongs beta-cell graft survival. Transpl Immunol 21:143–149 (PubMed:19361556)CrossRefPubMed Yuan CL, Xu JF, Tong J, Yang H, He FR, Gong Q, Xiong P, Duan L, Fang M, Tan Z, Xu Y, Chen YF, Zheng F, Gong FL (2009) B7-H4 transfection prolongs beta-cell graft survival. Transpl Immunol 21:143–149 (PubMed:19361556)CrossRefPubMed
21.
go back to reference Sun Y, Liu J, Cui X (2006) Clinical significance of expression of B7-H4 in colon and rectal cancer tissues. J Shandong Univ (Health Sci) 44:590–592 Sun Y, Liu J, Cui X (2006) Clinical significance of expression of B7-H4 in colon and rectal cancer tissues. J Shandong Univ (Health Sci) 44:590–592
22.
go back to reference De Vita F, Orditura M, Matano E, Bianco R, Carlomagno C, Infusino S, Damiano V, Simeone E, Diadema MR, Lieto E, Castellano P, Pepe S, De Placido S, Galizia G, Di Martino N, Ciardiello F, Catalano G, Bianco AR (2005) A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients. Br J Cancer 92:1644–1649 (PubMed:15856038)CrossRefPubMed De Vita F, Orditura M, Matano E, Bianco R, Carlomagno C, Infusino S, Damiano V, Simeone E, Diadema MR, Lieto E, Castellano P, Pepe S, De Placido S, Galizia G, Di Martino N, Ciardiello F, Catalano G, Bianco AR (2005) A phase II study of biweekly oxaliplatin plus infusional 5-fluorouracil and folinic acid (FOLFOX-4) as first-line treatment of advanced gastric cancer patients. Br J Cancer 92:1644–1649 (PubMed:15856038)CrossRefPubMed
23.
go back to reference Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KN, Masferrer J, Koki AT (2000) COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89:2637–2645 (PubMed:11135226)CrossRefPubMed Soslow RA, Dannenberg AJ, Rush D, Woerner BM, Khan KN, Masferrer J, Koki AT (2000) COX-2 is expressed in human pulmonary, colonic, and mammary tumors. Cancer 89:2637–2645 (PubMed:11135226)CrossRefPubMed
24.
go back to reference Hao L, Zhang C, Qiu Y, Wang L, Luo Y, Jin M, Zhang Y, Guo TB, Matsushima K, Zhang Y (2007) Recombination of CXCR4, VEGF, and MMP-9 predicting lymph node metastasis in human breast cancer. Cancer Lett 253:34–42 (PubMed:17306924)CrossRefPubMed Hao L, Zhang C, Qiu Y, Wang L, Luo Y, Jin M, Zhang Y, Guo TB, Matsushima K, Zhang Y (2007) Recombination of CXCR4, VEGF, and MMP-9 predicting lymph node metastasis in human breast cancer. Cancer Lett 253:34–42 (PubMed:17306924)CrossRefPubMed
25.
go back to reference Kamimura Y, Kobori H, Piao J, Hashiguchi M, Matsumoto K, Hirose S, Azuma M (2009) Possible involvement of soluble B7-H4 in T cell-mediated inflammatory immune responses. Biochem Biophys Res Commun 389:349–353 (PubMed:19723502)CrossRefPubMed Kamimura Y, Kobori H, Piao J, Hashiguchi M, Matsumoto K, Hirose S, Azuma M (2009) Possible involvement of soluble B7-H4 in T cell-mediated inflammatory immune responses. Biochem Biophys Res Commun 389:349–353 (PubMed:19723502)CrossRefPubMed
26.
go back to reference Aparicio T, Boige V, Sabourin JC, Crenn P, Ducreux M, Le Cesne A, Bonvalot S (2004) Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours. Eur J Surg Oncol 30:1098–1103 (PubMed:15522557)CrossRefPubMed Aparicio T, Boige V, Sabourin JC, Crenn P, Ducreux M, Le Cesne A, Bonvalot S (2004) Prognostic factors after surgery of primary resectable gastrointestinal stromal tumours. Eur J Surg Oncol 30:1098–1103 (PubMed:15522557)CrossRefPubMed
27.
go back to reference Prasad DV, Richards S, Mai XM, Dong C (2003) B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity 18:863–873 (PubMed:12818166)CrossRefPubMed Prasad DV, Richards S, Mai XM, Dong C (2003) B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity 18:863–873 (PubMed:12818166)CrossRefPubMed
28.
go back to reference Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, Chapoval AI, Flies DB, Bajorath J, Chen L (2003) B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity 18:849–861 (PubMed:12818165)CrossRefPubMed Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, Chapoval AI, Flies DB, Bajorath J, Chen L (2003) B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity 18:849–861 (PubMed:12818165)CrossRefPubMed
29.
go back to reference Zang X, Loke P, Kim J, Murphy K, Waitz R, Allison JP (2003) B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci USA 100:10388–10392 (PubMed:12920180)CrossRefPubMed Zang X, Loke P, Kim J, Murphy K, Waitz R, Allison JP (2003) B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci USA 100:10388–10392 (PubMed:12920180)CrossRefPubMed
30.
go back to reference Tringler B, Liu W, Corral L, Torkko KC, Enomoto T, Davidson S, Lucia MS, Heinz DE, Papkoff J, Shroyer KR (2006) B7-H4 overexpression in ovarian tumors. Gynecol Oncol 100:44–52 (PubMed:16256178)CrossRefPubMed Tringler B, Liu W, Corral L, Torkko KC, Enomoto T, Davidson S, Lucia MS, Heinz DE, Papkoff J, Shroyer KR (2006) B7-H4 overexpression in ovarian tumors. Gynecol Oncol 100:44–52 (PubMed:16256178)CrossRefPubMed
31.
go back to reference Simon I, Liu Y, Krall KL, Urban N, Wolfert RL, Kim NW, McIntosh MW (2007) Evaluation of the novel serum markers B7-H4, Spondin 2, and DcR3 for diagnosis and early detection of ovarian cancer. Gynecol Oncol 106:112–118 (PubMed:17490732)CrossRefPubMed Simon I, Liu Y, Krall KL, Urban N, Wolfert RL, Kim NW, McIntosh MW (2007) Evaluation of the novel serum markers B7-H4, Spondin 2, and DcR3 for diagnosis and early detection of ovarian cancer. Gynecol Oncol 106:112–118 (PubMed:17490732)CrossRefPubMed
32.
go back to reference Thompson RH, Zang X, Lohse CM, Leibovich BC, Slovin SF, Reuter VE, Cheville JC, Blute ML, Russo P, Kwon ED, Allison JP (2008) Serum-soluble B7x is elevated in renal cell carcinoma patients and is associated with advanced stage. Cancer Res 68:6054–6058 (PubMed:18676826)CrossRefPubMed Thompson RH, Zang X, Lohse CM, Leibovich BC, Slovin SF, Reuter VE, Cheville JC, Blute ML, Russo P, Kwon ED, Allison JP (2008) Serum-soluble B7x is elevated in renal cell carcinoma patients and is associated with advanced stage. Cancer Res 68:6054–6058 (PubMed:18676826)CrossRefPubMed
33.
go back to reference Krambeck AE, Thompson RH, Dong H, Lohse CM, Park ES, Kuntz SM, Leibovich BC, Blute ML, Cheville JC, Kwon ED (2006) B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival. Proc Natl Acad Sci USA 103:10391–10396 (PubMed:16798883)CrossRefPubMed Krambeck AE, Thompson RH, Dong H, Lohse CM, Park ES, Kuntz SM, Leibovich BC, Blute ML, Cheville JC, Kwon ED (2006) B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival. Proc Natl Acad Sci USA 103:10391–10396 (PubMed:16798883)CrossRefPubMed
34.
go back to reference Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA, Scardino PT, Sharma P, Allison JP (2007) B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci USA 104:19458–19463 (PubMed:18042703)CrossRefPubMed Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA, Scardino PT, Sharma P, Allison JP (2007) B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci USA 104:19458–19463 (PubMed:18042703)CrossRefPubMed
35.
go back to reference Wu CP, Jiang JT, Tan M, Zhu YB, Ji M, Xu KF, Zhao JM, Zhang GB, Zhang XG (2006) Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis. World J Gastroenterol 12:457–459 (PubMed:16489649)PubMed Wu CP, Jiang JT, Tan M, Zhu YB, Ji M, Xu KF, Zhao JM, Zhang GB, Zhang XG (2006) Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis. World J Gastroenterol 12:457–459 (PubMed:16489649)PubMed
36.
go back to reference Wu C, Zhu Y, Jiang J, Zhao J, Zhang XG, Xu N (2006) Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem 108:19–24 (PubMed:16530813)CrossRefPubMed Wu C, Zhu Y, Jiang J, Zhao J, Zhang XG, Xu N (2006) Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem 108:19–24 (PubMed:16530813)CrossRefPubMed
Metadata
Title
Tumor expression of B7-H4 predicts poor survival of patients suffering from gastric cancer
Authors
Jingting Jiang
Yibei Zhu
Changping Wu
Yueping Shen
Wenxiang Wei
Lujun Chen
Xiao Zheng
Jing Sun
Binfeng Lu
Xueguang Zhang
Publication date
01-11-2010
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 11/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-010-0900-7

Other articles of this Issue 11/2010

Cancer Immunology, Immunotherapy 11/2010 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine