B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma
B7-H4 expression associates with cancer progression and predicts patient's survival in human esophageal squamous cell carcinoma
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DOI：
10.1007/s00262-011-1017-3
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发表时间：
2011-07-01
影响因子：
5.8
通讯作者：
Zhang, Xue-guang
中科院分区：
文献类型：
--
作者：
Chen, Lu-jun;Sun, Jing;Zhang, Xue-guang
为探讨B7-H4在食管鳞状细胞癌（ESCC）中的表达及其与患者临床病理参数和生存期的关系，对112例ESCC患者进行了回顾性队列研究。采用免疫组化方法检测食管鳞癌手术标本中肿瘤细胞B7-H4表达水平和肿瘤浸润淋巴细胞（TIL）密度。进行单因素和多因素分析以评估肿瘤切片中B7-H4表达水平和TIL密度的预后价值。112例食管鳞癌组织切片中107例（95.5%）B7-H4免疫染色阳性。我们进一步将所有患者分为两个主要亚组，B7-H4低表达组46例，B7-H4高表达组66例。B7-H4表达水平与患者性别（P = 0.0288）、远处转移（P = 0.0500）、TNM分期（P = 0.0258）相关。肿瘤细胞B7-H4表达与肿瘤巢中CD 3 + T细胞密度（P = 0.0424）和肿瘤间质中CD 8 + T细胞密度（P = 0.0229）呈负相关。B7-H4高表达患者的总生存率显著低于B7-H4低表达患者（P = 0.0105，HazardRatio：1.854，95%CI：1.152-2.902）。细胞介导的免疫反应标志物（例如CD 3、CD 8和T-bet）与更好的患者生存相关。目前的研究表明，B7-H4在人ESCC中的表达与癌症进展、肿瘤免疫监视降低和患者预后不良相关。B7-H4可作为一种新的预测人食管鳞癌预后的指标，并可作为免疫治疗的潜在靶点。
A retrospective cohort study including 112 patients suffering from esophageal squamous cell carcinoma (ESCC) was performed to investigate the expression of B7-H4 in ESCC and determine its association with patient's clinicopathological parameters and survival. Expression levels of B7-H4 on tumor cells and densities of tumor infiltrating lymphocytes (TILs) in the surgical specimens of ESCC tissues were characterized using immunohistochemical assays. Uni- and multivariate analyses were performed to evaluate the prognostic value of B7-H4 expression levels and densities of TILs in tumor sections. Positive B7-H4 immunostaining was observed in 107 of 112 (95.5%) of ESCC tissue sections. We further divided all patients into two major subgroups, a lower B7-H4 expression group with 46 patients and a higher B7-H4 expression group with 66 patients. We found that expression levels of B7-H4 on tumor cells were significantly correlated with patient's gender (P = 0.0288), distant metastasis (P = 0.0500), and TNM stage (P = 0.0258). Moreover, tumor cell B7-H4 expression was inversely correlated with densities of CD3(+) T cells in tumor nest (P = 0.0424) and CD8(+) T cells in tumor stroma (P = 0.0229). The overall survival rate of the patients with higher B7-H4 expression was significantly worse than that of the patients with lower B7-H4 expression (P = 0.0105, Hazard Ratio: 1.854, 95%CI:1.152-2.902). Markers of cell-mediated immune responses such as CD3, CD8, and T-bet were associated with better patient survival. The present study demonstrated that B7-H4 expression in human ESCC is associated with cancer progression, reduced tumor immunosurveillance and worse patient outcomes. B7-H4 can serve as a novel prognostic predictor for human ESCC and a potential target for the immune therapy against this malignancy.