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B7-H1表达与人类食管癌的肿瘤侵袭相关,并可预测患者的生存情况。

B7-H1 expression associates with tumor invasion and predicts patient's survival in human esophageal cancer.

作者信息

Chen Lujun, Deng Haifeng, Lu Mingyang, Xu Bin, Wang Qi, Jiang Jingting, Wu Changping

机构信息

Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University Changzhou 213003, Jiangsu, China.

Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University Changzhou 213003, Jiangsu, China ; Department of Oncology, The Third Affiliated Hospital, Soochow University Changzhou 213003, Jiangsu, China.

出版信息

Int J Clin Exp Pathol. 2014 Aug 15;7(9):6015-23. eCollection 2014.

Abstract

B7-H1, an important member of the B7-CD28 super family, has been reported to play an important role in regulation of T-cell mediated anti-tumor response, and also has effect in the biological characteristics of the tumor cells themselves. The bulk of data indicate that cancer immunotherapy targeting the molecule B7-H1 recently has sparked growing interest. We have previously reported that higher expression of B7-H1 in human gastric cancer significantly associated with tumor size, invasion, nodal metastasis, survival and the density of infiltrating Foxp3(+) Tregs. In the present study, we used tissue microarray to further study B7-H1 expression in human esophageal cancer tissues and its clinical significance. We found that positive membranous B7-H1 expression could be found in some human esophageal cancer cell lines, and both membranous/cytoplasm and nuclear staining of B7-H1 could be found in esophageal cancer tissues. We demonstrated that the membranous/cytoplasm B7-H1 expression in human esophageal cancer tissues was significantly correlated with tumor invasion depth (P = 0.0261), whereas it was not correlated with patient's gender, age, tumor size, nodal metastasis, distant metastasis and TNM stage. The survival analysis showed that the overall survival of the patients with positive B7-H1 membrane/cytoplasm expression was significantly poorer than that of the patients with negative B7-H1 membrane/cytoplasm expression (Hazard ratio = 2.157, 95% CI: 1.017-4.577, P = 0.0452). Moreover, we also found that the nuclear B7-H1 expression in human esophageal cancer tissues was significantly correlated with tumor invasion depth (P = 0.0331), whereas it was not correlated with other parameters. The log-rank survival analysis showed that there was no statistically significant difference in prognosis between the patients with positive nuclear B7-H1 staining and the patients with negative nuclear B7-H1 staining (P = 0.6755). Thus, our data showed that B7-H1 can serve as a prognostic predictor for human esophageal cancer, and also could be an important therapeutic target for the immune therapy against this malignancy.

摘要

B7-H1是B7-CD28超家族的重要成员,据报道其在调节T细胞介导的抗肿瘤反应中发挥重要作用,并且对肿瘤细胞自身的生物学特性也有影响。大量数据表明,针对B7-H1分子的癌症免疫疗法最近引发了越来越多的关注。我们之前报道过,人胃癌中B7-H1的高表达与肿瘤大小、侵袭、淋巴结转移、生存率以及浸润性Foxp3(+)调节性T细胞的密度显著相关。在本研究中,我们使用组织芯片进一步研究人食管癌组织中B7-H1的表达及其临床意义。我们发现,在一些人食管癌细胞系中可检测到B7-H1的膜阳性表达,而在食管癌组织中可同时检测到B7-H1的膜/细胞质和细胞核染色。我们证明,人食管癌组织中膜/细胞质B7-H1的表达与肿瘤浸润深度显著相关(P = 0.0261),而与患者的性别、年龄、肿瘤大小、淋巴结转移、远处转移及TNM分期无关。生存分析显示,B7-H1膜/细胞质表达阳性患者的总生存期显著低于B7-H1膜/细胞质表达阴性患者(风险比=2.157,95%可信区间:1.017 - 4.577,P = 0.0452)。此外,我们还发现,人食管癌组织中细胞核B7-H1的表达与肿瘤浸润深度显著相关(P = 0.0331),而与其他参数无关。对数秩生存分析显示,细胞核B7-H1染色阳性患者与阴性患者的预后无统计学显著差异(P = 0.6755)。因此,我们的数据表明,B7-H1可作为人食管癌的预后预测指标,也可能是针对这种恶性肿瘤进行免疫治疗的重要靶点。

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