Cho Hanbyoul, Chung Joon-Yong, Kim Sunghoon, Braunschweig Till, Kang Tae Heung, Kim Jennie, Chung Eun Joo, Hewitt Stephen M, Kim Jae-Hoon
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, 146-92 Dogok-Dong, Gangnam-Gu, Seoul 135-720, Korea.
BMC Cancer. 2014 Dec 15;14:957. doi: 10.1186/1471-2407-14-957.
NKG2D (natural killer group 2, member D) is thought to play an important role in mediating the activation of anticancer immune response. Expression of NKG2D ligands (NKG2DLs) is pronounced in malignancies and the heterogeneity of NKG2DL expression remains unclear. Here, we investigate the expression and clinical significance of NKG2DLs in cervical cancer.
Immunohistochemical analyses of MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G were performed using tissue microarray analysis of 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues and compared the data with clinicopathologic variables, including the survival of cervical cancer patients.
MICA/B, ULBP1, and RAET1E expression was higher in cervical cancer than in low-grade CIN (p<0.001, p=0.012, p=0.013, respectively) and normal cervix (all p<0.001). Among these markers, expression of ULBP1 was significantly different depending on patient tumor stage (p=0.010) and tumor size (p=0.045). ULBP1 expression was correlated with MICA/B (p<0.001) and ULBP2 (p=0.002) expression in cervical cancer. While MICA/B+ or ULBP1+ patients had improved disease-free survival time (p=0.027 and p=0.009, respectively) relative to that of the low expression group, RAET1E+ or RAET1G+ was correlated with shorter survival time (p=0.018 and p=0.029, respectively). However, in terms of overall survival, the ULBP1+ group had significantly longer survival time than the low expression group (p=0.009). Multivariate analysis indicated that MICA/B+/ULBP1+ (HR=0.16, p=0.015) and ULBP1+ (HR=0.31, p=0.024) are independent prognostic factors of disease-free survival in cervical cancer.
High expression of either ULBP1 or MICA/B and ULBP1 combined is an indicator of good prognosis in cervical cancer, suggesting their potential utility as prognostic tests in clinical assessment.
自然杀伤细胞2族成员D（NKG2D）被认为在介导抗癌免疫反应激活中起重要作用。NKG2D配体（NKG2DLs）在恶性肿瘤中表达明显，但其表达的异质性仍不清楚。在此，我们研究NKG2DLs在宫颈癌中的表达及临床意义。
采用组织芯片分析对200例宫颈癌、327例高级别宫颈上皮内瘤变（CIN）、99例低级别CIN以及541例配对的非相邻正常宫颈上皮组织进行MICA/B、ULBP1、ULBP2、ULBP3、RAET1E和RAET1G的免疫组化分析，并将数据与临床病理变量进行比较，包括宫颈癌患者的生存率。
MICA/B、ULBP1和RAET1E在宫颈癌中的表达高于低级别CIN（分别为p<0.001、p=0.012、p=0.013）和正常宫颈（均p<0.001）。在这些标志物中，ULBP1的表达根据患者肿瘤分期（p=0.010）和肿瘤大小（p=0.045）有显著差异。在宫颈癌中，ULBP1表达与MICA/B（p<0.001）和ULBP2（p=0.002）表达相关。与低表达组相比，MICA/B+或ULBP1+患者的无病生存时间有所改善（分别为p=0.027和p=0.009），而RAET1E+或RAET1G+与较短的生存时间相关（分别为p=0.018和p=0.029）。然而，就总生存而言，ULBP1+组的生存时间明显长于低表达组（p=0.009）。多因素分析表明，MICA/B+/ULBP1+（HR=0.16，p=0.015）和ULBP1+（HR=0.31，p=0.024）是宫颈癌无病生存的独立预后因素。
ULBP1或MICA/B以及ULBP1联合高表达是宫颈癌预后良好的指标，表明它们在临床评估中作为预后检测的潜在效用。
