Shen Lingwei, Qian Yun, Wu Weigen, Weng Tianhao, Wang Frederick X C, Hong Bo, Wu Zhigang, Wang Qi, Sang Yiwen, Zhang Hong, Zhou Xinhui, Yao Hangping
Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
Hum Pathol. 2017 Aug;66:79-85. doi: 10.1016/j.humpath.2017.05.023. Epub 2017 Jun 23.
B7-H4 belongs to the immune costimulatory B7 family and is thought to negatively regulate T-cell-mediated immunity, and may contribute an important role in tumor immune evasion. Although the expression of B7-H4 has been observed in human pancreatic cancer, the prognostic significance of this expression is poorly understood. This present study explored the prognostic value of B7-H4 in pancreatic cancer. Patients with pancreatic cancer and healthy controls were recruited at the Second Affiliated Hospital to Zhejiang University from January 2011 to December 2014. Expression of B7-H4 was assessed by immunohistochemistry. Immunohistochemical analysis indicated that B7-H4 was expressed in 100% (188/188) of the pancreatic cancer tumor tissue samples, while only in 68% (17/25) of normal pancreatic tissue samples. Furthermore, the expression levels of B7-H4 in pancreatic cancer patients were significantly higher than in controls (P<.01). A significant difference in B7-H4 expression was observed between patients with late tumor-node-metastasis (TNM) stage (III and IV) and early TNM stage (I and II) (P<.01). The expression of B7-H4 was associated with distant metastasis (P<.01) and differentiation (P<.01). In addition, B7-H4 expression (P<.01), distant metastasis (P<.01), TNM stage (P<.01), differentiation (P<.01) and chemotherapy treatment (P<.05) were indicators of poor overall survival time. Multivariate survival analysis indicated that B7-H4 expression, distant metastasis, and chemotherapy treatment (P<.05) were independent prognostic indicators of poor overall survival. In conclusion, B7-H4 is highly expressed in pancreatic cancer, and is an independent predictor of poor prognosis in patients with pancreatic cancer. B7-H4 may represent an immunotherapeutic target in pancreatic cancer.
B7-H4属于免疫共刺激B7家族，被认为对T细胞介导的免疫起负调节作用，可能在肿瘤免疫逃逸中发挥重要作用。尽管在人类胰腺癌中已观察到B7-H4的表达，但其表达的预后意义仍知之甚少。本研究探讨了B7-H4在胰腺癌中的预后价值。2011年1月至2014年12月，在浙江大学医学院附属第二医院招募了胰腺癌患者和健康对照。通过免疫组织化学评估B7-H4的表达。免疫组织化学分析表明，B7-H4在100%（188/188）的胰腺癌肿瘤组织样本中表达，而仅在68%（17/25）的正常胰腺组织样本中表达。此外，胰腺癌患者中B7-H4的表达水平显著高于对照组（P<0.01）。在肿瘤-淋巴结-转移（TNM）晚期（III期和IV期）和早期TNM期（I期和II期）患者之间观察到B7-H4表达存在显著差异（P<0.01）。B7-H4的表达与远处转移（P<0.01）和分化（P<0.01）相关。此外，B7-H4表达（P<0.01）、远处转移（P<0.01）、TNM分期（P<0.01）、分化（P<0.01）和化疗治疗（P<0.05）是总体生存时间较差的指标。多因素生存分析表明B7-H4表达、远处转移和化疗治疗（P<0.05）是总体生存较差的独立预后指标。总之，B7-H4在胰腺癌中高表达，是胰腺癌患者预后不良的独立预测指标。B7-H4可能代表胰腺癌中的一个免疫治疗靶点。
