Expression and clinical significance of B7S1 in gastric cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

MAN Zhongsong ^1,2 , ZHAO Xin ¹ , LUAN Lipeng ¹ , ZHANG Zhe ¹ , SUN Mingbing ¹ , ZHANG Haitao ¹ ,  CHEN Bingxin ³

1. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P. R. China;
2. The Center of Hepatobiliary Pancreatic Disease, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, P. R. China;
3. Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P. R. China;

Corresponding author：

CHEN Bingxin, Email: ice_girl_1@163.com

Keywords：

gastric cancer; B7 superfamily member 1; tumor immunity; prognosis

DOI：

10.7507/1007-9424.201908019

Video：

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Objective To analyze the difference of expression of B7 superfamily member 1 (B7S1) in gastric cancer and adjacent cancer tissues, and to explore the relationship between B7S1 expression and the clinicopathological characteristics and the prognosis of gastric cancer patients.Methods Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were performed to investigate the expression of B7S1 in 78 cases of gastric cancer tissues and adjacent tissues. The correlation of B7S1 expressions with the clinicopathological characteristics and prognosis of the patients was analyzed.Results The results showed that cancer tissues relative expression of B7S1 mRNA was higher than that of adjacent tissues, and the difference was statistically significant (P<0.05). The results showed that positive rate of B7S1 protein expression in gastric cancer tissues was significantly higher than that of adjacent tissues, 74.36% and 11.54%, the difference was statistically significant (P=0.001). Chi-square analysis showed that the expression of B7S1 protein was associated with tumor diameter (P=0.006), pathological-stage (P=0.002), T-stage (P=0.011), and lymph node metastasis (P=0.001). There were no relationship with gender, age, tumor site, and M-stage (P>0.05). B7S1 protein expression was correlated with the overall survival rate for gastric cancer patients. Both univariate and Cox multivariate survival analysis suggested that B7S1 positive expression was a risk factor for poor prognosis in patients with gastric cancer.Conclusions The relative expression level of B7S1 mRNA and the positive rate of protein expression in gastric cancer tissues are higher than those in adjacent tissues. The positive expression of B7S1 is correlated with the poor clinicopathological characteristics and prognosis. We speculate that B7S1 may be involved in the malignant progression of gastric cancer.

Citation： MAN Zhongsong, ZHAO Xin, LUAN Lipeng, ZHANG Zhe, SUN Mingbing, ZHANG Haitao, CHEN Bingxin. Expression and clinical significance of B7S1 in gastric cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2020, 27(3): 284-290. doi: 10.7507/1007-9424.201908019 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol, 2005, 23: 515-548.
3.	Zang X, Allison JP. The B7 family and cancer therapy: costimulation and coinhibition. Clin Cancer Res, 2007, 13(18 Pt 1): 5271-5279.
4.	Welten SP, Redeker A, Franken KL, et al. The viral context instructs the redundancy of costimulatory pathways in driving CD8⁺ T cell expansion. Elife, 2015: 4.
5.	Ricciardi M, Zanotto M, Malpeli G, et al. Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells. Br J Cancer, 2015, 112(6): 1067-1075.
6.	Bronkhorst IH, Ly LV, Jordanova ES, et al. Detection of M2-macrophages in uveal melanoma and relation with survival. Invest Ophthalmol Vis Sci, 2011, 52(2): 643-650.
7.	Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med, 2012, 366(26): 2455-2465.
8.	Shen L, Qian Y, Wu W, et al. B7-H4 is a prognostic biomarker for poor survival in patients with pancreatic cancer. Hum Pathol, 2017, 66: 79-85.
9.	Zheng X, Li XD, Wu CP, et al. Expression of costimulatory molecule B7-H4 in human malignant tumors. Onkologie, 2012, 35(11): 700-705.
10.	Jiang J, Zhu Y, Wu C, et al. Tumor expression of B7-H4 predicts poor survival of patients suffering from gastric cancer. Cancer Immunol Immunother, 2010, 59(11): 1707-1714.
11.	Zhang C, Li Y, Wang Y. Diagnostic value of serum B7-H4 for hepatocellular carcinoma. J Surg Res, 2015, 197(2): 301-306.
12.	Shi H, Ji M, Wu J, et al. Serum B7-H4 expression is a significant prognostic indicator for patients with gastric cancer. World J Surg Oncol, 2014, 12: 188.
13.	American Joint committee on Cancer. Chapter 17. Stiamch//AJCC Cancer Staging Manual. 8th ed. New York: Springer, 2016: 203-220.
14.	De Ruysscher D, Niedermann G, Burnet NG, et al. Radiotherapy toxicity. Nat Rev Dis Primers, 2019, 5(1): 13.
15.	Podojil JR, Miller SD. Potential targeting of B7-H4 for the treatment of cancer. Immunol Rev, 2017, 276(1): 40-51.
16.	Zang X, Loke P, Kim J, et al. B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci U S A, 2003, 100(18): 10388-10392.
17.	Yao Y, Ye H, Qi Z, et al. B7-H4(B7x)-mediated cross-talk between glioma-initiating cells and macrophages via the IL6/JAK/STAT3 pathway lead to poor prognosis in glioma patients. Clin Cancer Res, 2016, 22(11): 2778-2790.
18.	Sica GL, Choi IH, Zhu G, et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity, 2003, 18(6): 849-861.
19.	Prasad DV, Richards S, Mai XM, et al. B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity, 2003, 18(6): 863-873.
20.	Choi IH, Zhu G, Sica GL, et al. Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol, 2003, 171(9): 4650-4654.
21.	Anderson HA, Hiltb EM, Roche PA. Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation. Nat Immunol, 2000, 1(2): 156-162.
22.	Guo L, Liu Z, Zhang Y, et al. Association of increased B7 protein expression by infiltrating immune cells with progression of gastric carcinogenesis. Medicine (Baltimore), 2019, 98(8): e14663.
23.	Zhou D, Zhou Y, Li C, et al. Silencing of B7-H4 suppresses the tumorigenicity of the MGC-803 human gastric cancer cell line and promotes cell apoptosis via the mitochondrial signaling pathway. Int J Oncol, 2018, 52(4): 1267-1276.
24.	Chen X, Tao L, Yuan C, et al. The prognostic value of B7-H4 in pancreatic cancer: Systematic review and meta-analysis. Medicine, 2018, 97(12): e0088.
25.	Wang P, Li C, Zhang F, et al. Clinical value of combined determination of serum B7-H4 with carcinoembryonic antigen, osteopontin, or tissue polypeptide-specific antigen for the diagnosis of colorectal cancer. Dis Markers, 2018, 2018: 4310790.
26.	Zhang SA, Wu ZX, Zhang X, et al. Circulating B7-H4 in serum predicts prognosis in patients with hepatocellular carcinoma. Genet Mol Res, 2015, 14(4): 13041-13048.
27.	Li J, Lee Y, Li Y, et al. Co-inhibitory molecule B7 superfamily member 1 expressed by tumor-infiltrating myeloid cells induces dysfunction of anti-tumor CD8+ T cells. Immunity, 2018, 48(4): 773-786.
28.	Chen LJ, Sun J, Wu HY, et al. B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma. Cancer Immunol Immunother, 2011, 60(7): 1047-1055.
29.	Xu H, Chen X, Tao M, et al. B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer. Oncol Lett, 2016, 11(3): 1841-1846.
30.	Goode EF, Smyth EC. Immunotherapy for gastroesophageal cancer. J Clin Med, 2016, 5(10): pii: E84.
31.	Mugler KC, Singh M, Tringler B, et al. B7-h4 expression in a range of breast pathology: correlation with tumor T-cell infiltration. Appl Immunohistochem Mol Morphol, 2007, 15(4): 363-370.
32.	Ye Y, Wang JJ, Li SL, et al. Does B7-H4 expression correlate with clinicopathologic characteristics and survival in ovarian cancer?: A systematic review and PRISMA-compliant meta-analysis. Medicine (Baltimore), 2018, 97(32): e11821.
33.	Carvajal-Hausdorf D, Altan M, Velcheti V, et al. Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC). J Immunother Cancer, 2019, 7(1): 65.
34.	梁克, 谢锐, 张万青, 等. B7-H4 和细胞分裂周期蛋白 42 在非小细胞肺癌组织中的表达及其临床意义. 中华实验外科杂志, 2016, 33(8): 1903-1905.
35.	Azuma T, Sato Y, Ohno T, et al. Serum soluble B7-H4 is a prognostic marker for patients with non-metastatic clear cell renal cell carcinoma. PLoS One, 2018, 13(7): e0199719.
36.	Ribas A, Hamid O, Daud A, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA, 2016, 315(15): 1600-1609.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol, 2005, 23: 515-548.
3. Zang X, Allison JP. The B7 family and cancer therapy: costimulation and coinhibition. Clin Cancer Res, 2007, 13(18 Pt 1): 5271-5279.
4. Welten SP, Redeker A, Franken KL, et al. The viral context instructs the redundancy of costimulatory pathways in driving CD8⁺ T cell expansion. Elife, 2015: 4.
5. Ricciardi M, Zanotto M, Malpeli G, et al. Epithelial-to-mesenchymal transition (EMT) induced by inflammatory priming elicits mesenchymal stromal cell-like immune-modulatory properties in cancer cells. Br J Cancer, 2015, 112(6): 1067-1075.
6. Bronkhorst IH, Ly LV, Jordanova ES, et al. Detection of M2-macrophages in uveal melanoma and relation with survival. Invest Ophthalmol Vis Sci, 2011, 52(2): 643-650.
7. Brahmer JR, Tykodi SS, Chow LQ, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med, 2012, 366(26): 2455-2465.
8. Shen L, Qian Y, Wu W, et al. B7-H4 is a prognostic biomarker for poor survival in patients with pancreatic cancer. Hum Pathol, 2017, 66: 79-85.
9. Zheng X, Li XD, Wu CP, et al. Expression of costimulatory molecule B7-H4 in human malignant tumors. Onkologie, 2012, 35(11): 700-705.
10. Jiang J, Zhu Y, Wu C, et al. Tumor expression of B7-H4 predicts poor survival of patients suffering from gastric cancer. Cancer Immunol Immunother, 2010, 59(11): 1707-1714.
11. Zhang C, Li Y, Wang Y. Diagnostic value of serum B7-H4 for hepatocellular carcinoma. J Surg Res, 2015, 197(2): 301-306.
12. Shi H, Ji M, Wu J, et al. Serum B7-H4 expression is a significant prognostic indicator for patients with gastric cancer. World J Surg Oncol, 2014, 12: 188.
13. American Joint committee on Cancer. Chapter 17. Stiamch//AJCC Cancer Staging Manual. 8th ed. New York: Springer, 2016: 203-220.
14. De Ruysscher D, Niedermann G, Burnet NG, et al. Radiotherapy toxicity. Nat Rev Dis Primers, 2019, 5(1): 13.
15. Podojil JR, Miller SD. Potential targeting of B7-H4 for the treatment of cancer. Immunol Rev, 2017, 276(1): 40-51.
16. Zang X, Loke P, Kim J, et al. B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci U S A, 2003, 100(18): 10388-10392.
17. Yao Y, Ye H, Qi Z, et al. B7-H4(B7x)-mediated cross-talk between glioma-initiating cells and macrophages via the IL6/JAK/STAT3 pathway lead to poor prognosis in glioma patients. Clin Cancer Res, 2016, 22(11): 2778-2790.
18. Sica GL, Choi IH, Zhu G, et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity, 2003, 18(6): 849-861.
19. Prasad DV, Richards S, Mai XM, et al. B7S1, a novel B7 family member that negatively regulates T cell activation. Immunity, 2003, 18(6): 863-873.
20. Choi IH, Zhu G, Sica GL, et al. Genomic organization and expression analysis of B7-H4, an immune inhibitory molecule of the B7 family. J Immunol, 2003, 171(9): 4650-4654.
21. Anderson HA, Hiltb EM, Roche PA. Concentration of MHC class II molecules in lipid rafts facilitates antigen presentation. Nat Immunol, 2000, 1(2): 156-162.
22. Guo L, Liu Z, Zhang Y, et al. Association of increased B7 protein expression by infiltrating immune cells with progression of gastric carcinogenesis. Medicine (Baltimore), 2019, 98(8): e14663.
23. Zhou D, Zhou Y, Li C, et al. Silencing of B7-H4 suppresses the tumorigenicity of the MGC-803 human gastric cancer cell line and promotes cell apoptosis via the mitochondrial signaling pathway. Int J Oncol, 2018, 52(4): 1267-1276.
24. Chen X, Tao L, Yuan C, et al. The prognostic value of B7-H4 in pancreatic cancer: Systematic review and meta-analysis. Medicine, 2018, 97(12): e0088.
25. Wang P, Li C, Zhang F, et al. Clinical value of combined determination of serum B7-H4 with carcinoembryonic antigen, osteopontin, or tissue polypeptide-specific antigen for the diagnosis of colorectal cancer. Dis Markers, 2018, 2018: 4310790.
26. Zhang SA, Wu ZX, Zhang X, et al. Circulating B7-H4 in serum predicts prognosis in patients with hepatocellular carcinoma. Genet Mol Res, 2015, 14(4): 13041-13048.
27. Li J, Lee Y, Li Y, et al. Co-inhibitory molecule B7 superfamily member 1 expressed by tumor-infiltrating myeloid cells induces dysfunction of anti-tumor CD8+ T cells. Immunity, 2018, 48(4): 773-786.
28. Chen LJ, Sun J, Wu HY, et al. B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma. Cancer Immunol Immunother, 2011, 60(7): 1047-1055.
29. Xu H, Chen X, Tao M, et al. B7-H3 and B7-H4 are independent predictors of a poor prognosis in patients with pancreatic cancer. Oncol Lett, 2016, 11(3): 1841-1846.
30. Goode EF, Smyth EC. Immunotherapy for gastroesophageal cancer. J Clin Med, 2016, 5(10): pii: E84.
31. Mugler KC, Singh M, Tringler B, et al. B7-h4 expression in a range of breast pathology: correlation with tumor T-cell infiltration. Appl Immunohistochem Mol Morphol, 2007, 15(4): 363-370.
32. Ye Y, Wang JJ, Li SL, et al. Does B7-H4 expression correlate with clinicopathologic characteristics and survival in ovarian cancer?: A systematic review and PRISMA-compliant meta-analysis. Medicine (Baltimore), 2018, 97(32): e11821.
33. Carvajal-Hausdorf D, Altan M, Velcheti V, et al. Expression and clinical significance of PD-L1, B7-H3, B7-H4 and TILs in human small cell lung Cancer (SCLC). J Immunother Cancer, 2019, 7(1): 65.
34. 梁克, 谢锐, 张万青, 等. B7-H4 和细胞分裂周期蛋白 42 在非小细胞肺癌组织中的表达及其临床意义. 中华实验外科杂志, 2016, 33(8): 1903-1905.
35. Azuma T, Sato Y, Ohno T, et al. Serum soluble B7-H4 is a prognostic marker for patients with non-metastatic clear cell renal cell carcinoma. PLoS One, 2018, 13(7): e0199719.
36. Ribas A, Hamid O, Daud A, et al. Association of pembrolizumab with tumor response and survival among patients with advanced melanoma. JAMA, 2016, 315(15): 1600-1609.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression and clinical significance of B7S1 in gastric cancer

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