Zhou Yi, Xu Yun, Chen Lujun, Xu Bin, Wu Changping, Jiang Jingting
Department of Tumor Biological Treatment, The Third Affiliated Hospital Soochow University Changzhou 213003, Jiangsu, China ; Jiangsu Engineering Research Center for Tumor Immunotherapy, 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 ; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital Soochow University Changzhou 213003, Jiangsu, China ; Department of Gynecology, The Third Affiliated Hospital Soochow University Changzhou 213003, Jiangsu, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9428-33. eCollection 2015.
B7-H6, a newly identified B7 family member molecule, binds to its receptor on NK cells, NKp30, and then triggers the anti-tumor NK cell cytotoxicity and leads to the cytokine secretion. As of now, numerous studies have demonstrated that the higher B7-H6 expression could be found in certain human cancers and have important clinical significance. In our present study, we carried out the tissue microarray and the immunohistochemistry assay to investigate the clinical significance of B7-H6 expression in human ovarian cancer. Our results showed that the positive B7-H6 staining was predominantly observed on the membrane and in the cytoplasm of the ovarian cancer cells. In order to further investigate the correlation between clinical parameters and the B7-H6 protein levels in the ovarian tissues, we categorized all the 110 patients into two major subgroups according to the intensity of B7-H6 immunohistochemical staining, i.e., the lower B7-H6 expression group, 34 cases (0 ≤ H-score < 100), and the higher B7-H6 expression group, 76 cases (H-score ≥ 100), and we found that B7-H6 expression in the ovarian cancer tissues is significantly correlated with distant metastasis status (P = 0.028) and FIGO stage (P = 0.031), whereas it is not correlated with patient's age, tumor size, tumor location, pathological stage or nodal metastasis. The survival analysis demonstrated that the overall survival rate of the subgroup with lower B7-H6 expression is significantly better than that of the subgroup with higher B7-H6 expression (P = 0.0456, Hazard Ratio: 1.707, 95% CI, 1.010-2.885). Thus, our present data revealed that higher B7-H6 expression in ovarian cancer tissues was positively correlated with tumor metastasis and cancer progression, and supports the notion that B7-H6 expression is involved in the progression of human ovarian cancer, the detailed mechanism merits further investigation.
B7-H6是一种新发现的B7家族成员分子,它与自然杀伤细胞(NK细胞)上的受体NKp30结合,进而触发抗肿瘤NK细胞的细胞毒性并导致细胞因子分泌。截至目前,大量研究表明,在某些人类癌症中可发现较高的B7-H6表达,且具有重要的临床意义。在我们目前的研究中,我们进行了组织芯片和免疫组化分析,以探讨B7-H6表达在人类卵巢癌中的临床意义。我们的结果显示,B7-H6阳性染色主要见于卵巢癌细胞的细胞膜和细胞质。为了进一步研究临床参数与卵巢组织中B7-H6蛋白水平之间的相关性,我们根据B7-H6免疫组化染色强度将110例患者分为两个主要亚组,即B7-H6低表达组,34例(0≤H评分<100),和B7-H6高表达组,76例(H评分≥100),我们发现卵巢癌组织中的B7-H6表达与远处转移状态(P = 0.028)和国际妇产科联盟(FIGO)分期(P = 0.031)显著相关,而与患者年龄、肿瘤大小、肿瘤位置、病理分期或淋巴结转移无关。生存分析表明,B7-H6低表达亚组的总生存率显著优于B7-H6高表达亚组(P = 0.0456,风险比:1.707,95%置信区间,1.010 - 2.885)。因此,我们目前的数据显示,卵巢癌组织中较高的B7-H6表达与肿瘤转移和癌症进展呈正相关,并支持B7-H6表达参与人类卵巢癌进展这一观点,其详细机制值得进一步研究。