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Article

B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer

  • Authors:
    • Hong Xu
    • Xiaoling Chen
    • Min Tao
    • Kai Chen
    • Chen Chen
    • Gang Xu
    • Wei Li
    • Suxu Yuan
    • Yixiang Mao
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215007, P.R. China, Department of Gastroenterology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China
  • Pages: 1841-1846
    |
    Published online on: January 19, 2016
       https://doi.org/10.3892/ol.2016.4128
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Abstract

B7-H3 and B7-H4 belong to the peripheral membrane protein B7 family and are hypothesized to regulate immunity. These proteins are expressed in human pancreatic cancer (PC), but their prognostic significance is poorly understood. The present study examined the association between B7‑H3 and B7‑H4 expression and the overall survival time in patients with PC that underwent surgery at the Second Affiliated Hospital to Zhengzhou University between April 2000 and January 2009. Immunohistochemical analysis demonstrated that B7‑H3 and B7‑H4 were expressed in 35 (88%) and 30 (75%) tumor tissue samples, respectively, which were obtained from 40 patients with PC. Statistical analysis revealed that B7‑H3 expression was associated with an early tumor‑node‑metastasis stage (stage I and II; P<0.01), and B7‑H4 expression was associated with tumors located in the body and tail of the pancreas (P<0.01) and lymph node metastasis (P=0.02). In addition, using Spearman's rank correlation coefficient, the present study demonstrated a positive correlation between B7‑H3 expression and B7‑H4 expression (r=0.37; P=0.02) in tumor samples. B7‑H4 expression (P=0.01), tumors located in the pancreatic body and tail (P<0.01), lymph node metastasis (P=0.02) and combined B7‑H3 and B7‑H4 expression (P<0.01) were indicators of a poor overall survival time. However, solitary B7‑H4 expression (P=0.03) and combined B7‑H3 and B7‑H4 expression (P=0.04) remained significant prognostic factors following adjustment for other prognostic factors in a multivariate Cox's proportional hazards regression model. Therefore, the present results indicate that solitary B7‑H4 expression and a combination of B7‑H3 and B7‑H4 expression are independent predictors of a poor prognosis in patients with PC.
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1 

Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, Vauthey JN, Abdalla EK, Crane CH, Wolff RA, et al: Borderline resectable pancreatic cancer: The importance of this emerging stage of disease. J Am Coll Surg. 206:833–846. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Geer RJ and Brennan MF: Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 165:68–72. 1993. View Article : Google Scholar : PubMed/NCBI

4 

Nagaraj S, Gupta K, Pisarev V, Kinarsky L, Sherman S, Kang L, Herber DL, Schneck J and Gabrilovich DI: Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med. 13:828–835. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Zou W: Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 5:263–274. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Greenwald RJ, Freeman GJ and Sharpe AH: The B7 family revisited. Annu Rev Immunol. 23:515–548. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Subudhi SK, Alegre ML and Fu YX: The balance of immune responses: Costimulation verse coinhibition. J Mol Med Berl. 83:193–202. 2005. View Article : Google Scholar : PubMed/NCBI

8 

Driessens G, Kline J and Gajewski TF: Costimulatory and coinhibitory receptors in anti-tumor immunity. Immunol Rev. 229:126–144. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Chapoval AI, Ni J, Lau JS, Wilcox RA, Flies DB, Liu D, Dong H, Sica GL, Zhu G, Tamada K and Chen L: B7-H3: A costimulatory molecule for T cell activation and IFN-gamma production. Nat Immunol. 2:269–274. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Prasad DV, Nguyen T, Li Z, Yang Y, Duong J, Wang Y and Dong C: Murine B7-H3 is a negative regulator of T cells. J Immunol. 173:2500–2506. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Suh WK, Gajewska BU, Okada H, Gronski MA, Bertram EM, Dawicki W, Duncan GS, Bukczynski J, Plyte S, Elia A, et al: The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses. Nat Immunol. 4:899–906. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Wu CP, Jiang JT, Tan M, Zhu YB, Ji M, Xu KF, Zhao JM, Zhang GB and Zhang XG: Relationship between co-stimulatory molecule B7-H3 expression and gastric carcinoma histology and prognosis. World J Gastroenterol. 12:457–459. 2006.PubMed/NCBI

13 

Sun Y, Wang Y, Zhao J, Gu M, Giscombe R, Lefvert AK and Wang X: B7-H3 and B7-H4 expression in non-small-cell lung cancer. Lung Cancer. 53:143–151. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Crispen PL, Sheinin Y, Roth TJ, Lohse CM, Kuntz SM, Frigola X, Thompson RH, Boorjian SA, Dong H, Leibovich BC, et al: Tumor cell and tumor vasculature expression of B7-H3 predict survival in clear cell renal cell carcinoma. Clin Cancer Res. 14:5150–5157. 2008. View Article : Google Scholar : PubMed/NCBI

15 

Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA, Scardino PT, Sharma P and Allison JP: 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. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Yamato I, Sho M, Nomi T, Akahori T, Shimada K, Hotta K, Kanehiro H, Konishi N, Yagita H and Nakajima Y: Clinical importance of B7-H3 expression in human pancreatic cancer. Br J Cancer. 101:1709–1716. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Prasad DV, Richards S, Mai XM and Dong C: B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity. 18:863–873. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Tringler B, Zhuo S, Pilkington G, Torkko KC, Singh M, Lucia MS, Heinz DE, Papkoff J and Shroyer KR: B7-H4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res. 11:1842–1848. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Tringler B, Liu W, Corral L, Torkko KC, Enomoto T, Davidson S, Lucia MS, Heinz DE, Papkoff J and Shroyer KR: B7-H4 overexpression in ovarian tumors. Gynecol Oncol. 100:44–52. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Krambeck AE, Thompson RH, Dong H, Lohse CM, Park ES, Kuntz SM, Leibovich BC, Blute ML, Cheville JC and Kwon ED: B7-H4 expression in renal cell carcinoma and tumor vasculature: Associations with cancer progression and survival. Proc Natl Acad Sci USA. 103:10391–10396. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Awadallah NS, Shroyer KR, Langer DA, Torkko KC, Chen YK, Bentz JS, Papkoff J, Liu W, Nash SR and Shah RJ: Detection of B7-H4 and p53 in pancreatic cancer: Potential role as a cytological diagnostic adjunct. Pancreas. 36:200–206. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Greene FL, Page DL, Fleming ID, Fritz AG, Balch CM, Haller DG and Morrow M: Exocrine pancreas. AJCC Cancer Staging Manual (6th). (New York, NY). Springer. 157–164. 2002.

23 

Klöppel G, Hruban RH, Longneck DS, Adler G, Kern SE and Partanen TJ: Tumours of the exocrine pancreas. In: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. Hamilton SR and Aaltonen LA: 2:(Lyon). IARC Press. 219–252. 2000.

24 

Zhou YH, Chen YJ, Ma ZY, Xu L, Wang Q, Zhang GB, Xie F, Ge Y, Wang XF and Zhang XG: 4IgB7-H3 is the major isoform expressed on immunocytes as well as malignant cells. Tissue Antigens. 70:96–104. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Chen LJ, Sun J, Wu HY, Zhou SM, Tan Y, Tan M, Shan BE, Lu BF and Zhang XG: B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma. Cancer Immunol Immunother. 60:1047–1055. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Fauci JM, Straughn JM Jr, Ferrone S and Buchsbaum DJ: A review of B7-H3 and B7-H4 immune molecules and their role in ovarian cancer. Gynecol Oncol. 127:420–425. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Yi KH and Chen L: Fine tuning the immune response through B7-H3 and B7-H4. Immunol Rev. 229:145–151. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Chen XL, Yuan SX, Chen C, Mao YX, Xu G and Wang XY: Expression of B7-H1 protein in human pancreatic carcinoma tissues and its clinical significance. Ai Zheng. 28:1328–1332. 2009.(In Chinese). PubMed/NCBI

29 

Nomi T, Sho M, Akahori T, Hamada K, Kubo A, Kanehiro H, Nakamura S, Enomoto K, Yagita H, Azuma M and Nakajima Y: Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res. 13:2151–2157. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Qian Y, Hong B, Shen L, Wu Z, Yao H and Zhang L: B7-H4 enhances oncogenicity and inhibits apoptosis in pancreatic cancer cells. Cell Tissue Res. 353:139–151. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Roth TJ, Sheinin Y, Lohse CM, Kuntz SM, Frigola X, Inman BA, Krambeck AE, McKenney ME, Karnes RJ, Blute ML, et al: B7-H3 ligand expression by prostate cancer: A novel marker of prognosis and potential target for therapy. Cancer Res. 67:7893–7900. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, Wu C and Zheng L: Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med. 206:1327–1337. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Mugler KC, Singh M, Tringler B, Torkko KC, Liu W, Papkoff J and Shroyer KR: B7-H4 expression in a range of breast pathology: Correlation with tumor T cell infiltration. Appl Immunohistochem Mol Morphol. 15:363–370. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Simon I, Katsaros D, de la Longrais Rigault I, Massobrio M, Scorilas A, Kim NW, Sarno MJ, Wolfert RL and Diamandis EP: B7-H4 is over-expressed in early-stage ovarian cancer and is independent of CA125 expression. Gynecol Oncol. 106:334–341. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Choi IH, Zhu G, Sica GL, Strome SE, Cheville JC, Lau JS, Zhu Y, Flies DB, Tamada K and Chen L: Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol. 171:4650–4654. 2003. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xu H, Chen X, Tao M, Chen K, Chen C, Xu G, Li W, Yuan S and Mao Y: B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer. Oncol Lett 11: 1841-1846, 2016.
APA
Xu, H., Chen, X., Tao, M., Chen, K., Chen, C., Xu, G. ... Mao, Y. (2016). B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer. Oncology Letters, 11, 1841-1846. https://doi.org/10.3892/ol.2016.4128
MLA
Xu, H., Chen, X., Tao, M., Chen, K., Chen, C., Xu, G., Li, W., Yuan, S., Mao, Y."B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer". Oncology Letters 11.3 (2016): 1841-1846.
Chicago
Xu, H., Chen, X., Tao, M., Chen, K., Chen, C., Xu, G., Li, W., Yuan, S., Mao, Y."B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer". Oncology Letters 11, no. 3 (2016): 1841-1846. https://doi.org/10.3892/ol.2016.4128
Copy and paste a formatted citation
x
Spandidos Publications style
Xu H, Chen X, Tao M, Chen K, Chen C, Xu G, Li W, Yuan S and Mao Y: B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer. Oncol Lett 11: 1841-1846, 2016.
APA
Xu, H., Chen, X., Tao, M., Chen, K., Chen, C., Xu, G. ... Mao, Y. (2016). B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer. Oncology Letters, 11, 1841-1846. https://doi.org/10.3892/ol.2016.4128
MLA
Xu, H., Chen, X., Tao, M., Chen, K., Chen, C., Xu, G., Li, W., Yuan, S., Mao, Y."B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer". Oncology Letters 11.3 (2016): 1841-1846.
Chicago
Xu, H., Chen, X., Tao, M., Chen, K., Chen, C., Xu, G., Li, W., Yuan, S., Mao, Y."B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer". Oncology Letters 11, no. 3 (2016): 1841-1846. https://doi.org/10.3892/ol.2016.4128
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