Mizumori Osamu, Zembutsu Hitoshi, Kato Yoichiro, Tsunoda Tatsuhiko, Miya Fuyuki, Morizono Takashi, Tsukamoto Taiji, Fujioka Tomoaki, Tomita Yoshihiko, Kitamura Tadaichi, Ozono Seiichiro, Miki Tsuneharu, Naito Seiji, Akaza Hideyuki, Nakamura Yusuke
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639;
Exp Ther Med. 2010 Nov;1(6):955-961. doi: 10.3892/etm.2010.148. Epub 2010 Sep 10.
Interleukin (IL)-2 and interferon (IFN)-α combination therapy for metastatic renal cell carcinoma (RCC) improves the prognosis for a subset of patients, while some patients suffer from severe adverse drug reactions with little benefit. To establish a method to predict responses to this combination therapy (approximately 30% response rate), the gene expression profiles of primary RCCs were analyzed using an oligoDNA microarray consisting of 38,500 genes or ESTs, after enrichment of the cancer cell population by laser micro-beam microdissection. The analysis of 10 responders and 18 non-responders identified 24 genes that exhibited significant differential expression between the two groups. In addition, the patients whose tumors did not express HLA-DQA1 or HLA-DQB1 molecules demonstrated poor clinical response. Exclusion of patients with tumors lacking either of these two genes is likely to improve the response rate to IL-2 and IFN-α combination therapy from 30 to 67%, indicating that a simple pretreatment test provides useful information with which to subselect patients with renal cancer in order to improve the efficacy of this treatment and reduce unnecessary medical costs.
白细胞介素（IL）-2与干扰素（IFN）-α联合治疗转移性肾细胞癌（RCC）可改善部分患者的预后，然而一些患者会出现严重的药物不良反应且获益甚微。为建立一种预测该联合治疗反应的方法（反应率约为30%），在用激光微束显微切割富集癌细胞群体后，使用包含38,500个基因或EST的寡核苷酸DNA微阵列分析原发性RCC的基因表达谱。对10例反应者和18例无反应者的分析确定了24个在两组间表现出显著差异表达的基因。此外，肿瘤不表达HLA-DQA1或HLA-DQB1分子的患者临床反应较差。排除这两个基因中任一基因缺失的肿瘤患者可能会使IL-2与IFN-α联合治疗的反应率从30%提高到67%，这表明一个简单的预处理检测可为选择肾癌患者提供有用信息，以提高该治疗的疗效并降低不必要的医疗成本。
