Zhang Xiang, Yan Lei, Jiao Wei, Ren Juchao, Xing Naidong, Zhang Yongzhen, Zang Yuanwei, Wang Jue, Xu Zhonghua
Department of Urology, Qilu Hospital, Shandong University, 107 Wenhua West Road, Jinan, 250012, China.
Central Laboratory, The Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, 250033, China.
Tumour Biol. 2016 Feb;37(2):2153-9. doi: 10.1007/s13277-015-4041-7. Epub 2015 Sep 9.
Major histocompatibility complex class I-related chains A (MICA), a ligand of Natural killer group 2, member D (NKG2D) receptor, is broadly upregulated in epithelial originated tumor cells. MICA plays a critical role in the immune surveillance against tumor cells and is associated with the prognosis of several malignancies. The aim of this study is to evaluate the clinical and biological significance of MICA in clear cell renal cell carcinoma (ccRCC). The expression of MICA was analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Both MICA mRNA and protein levels were upregulated in ccRCC tissues, compared with normal tissues. IHC staining revealed a homogenous pattern of MICA staining within each tumor, which combined both membrane staining and granular cytoplasmic staining. Furthermore, high MICA expression was associated with lymph node metastasis and advanced clinical stage and predicted poor prognosis in patients with ccRCC. Gene set enrichment analysis (GSEA) was performed using RNA-sequencing data from The Cancer Genome Atlas Research Network (TCGA) to elucidate the biological role of MICA in ccRCC and revealed that MICA was significantly associated with the epithelial-to-mesenchymal transition (EMT) gene set, which was further confirmed by qRT-PCR. Our findings contribute to the studies on biomarkers of kidney cancers and the mechanism of renal cancer progression driven by EMT pathway.
主要组织相容性复合体I类相关链A(MICA)是自然杀伤细胞2族D成员(NKG2D)受体的配体,在上皮起源的肿瘤细胞中广泛上调。MICA在针对肿瘤细胞的免疫监视中起关键作用,并与几种恶性肿瘤的预后相关。本研究的目的是评估MICA在透明细胞肾细胞癌(ccRCC)中的临床和生物学意义。通过定量实时PCR(qRT-PCR)和免疫组织化学(IHC)分析MICA的表达。与正常组织相比,ccRCC组织中MICA mRNA和蛋白水平均上调。免疫组织化学染色显示每个肿瘤内MICA染色呈均匀模式,包括膜染色和颗粒状细胞质染色。此外,高MICA表达与淋巴结转移和临床晚期相关,并预测ccRCC患者预后不良。使用来自癌症基因组图谱研究网络(TCGA)的RNA测序数据进行基因集富集分析(GSEA),以阐明MICA在ccRCC中的生物学作用,结果显示MICA与上皮-间质转化(EMT)基因集显著相关,这通过qRT-PCR进一步得到证实。我们的研究结果有助于肾癌生物标志物的研究以及EMT途径驱动的肾癌进展机制的研究。