Duke Institute for Genome Sciences and Policy, Department of Internal Medicine, Duke University Medical Center, Durham, North Carolina, USA.
Cancer Invest. 2010 Aug;28(7):765-73. doi: 10.3109/07357900903095755.
The host immune response can impact cancer growth, prognosis, and response to therapy. In colorectal cancer, the presence of cells involved with T-cell-mediated adaptive immunity predicts survival better than the current staging method. We used the expression of genes recently associated with host immune responses (T(H1)-mediated adaptive immunity, inflammation, and immune suppression) to perform hierarchical clustering of multiple large cohorts of cancer specimens to determine if immune-related gene expression resulted in clinical significant groupings of tumors. Microarray data from prostate cancer (n = 79), breast cancer (n = 132), lung cancer (n = 84), glioblastoma multiforme (n = 120), and lymphoma (n = 127) were analyzed. Among adenocarcinomas, the T(H1)-mediated adaptive immunity genes were consistently associated with better prognosis, while genes associated with inflammation and immune suppression were variably associated with outcome. Specifically, increased expression of the T(H1)-mediated adaptive immunity genes was associated with good prognosis in breast cancer patients under 45 years of age (p = .04, hazard ratio [HR] = 0.42) and in prostate cancer patients (p = .03, HR = 0.36) but not in lung cancer patients (p = 0.45, HR = 1.37). In lymphoma, patients with increased expression of inflammation and immune suppression genes had better prognosis than those expressing the T(H1)-mediated adaptive immunity genes (p = .01, HR = 0.43) and in glioblastoma multiforme, the expression of inflammation genes conferred improved prognosis than those expressing immune suppression genes (p = 0.05, HR = 0.62). In aggregate, the gene expression signatures implicating specific components of the immune response hold prognostic import across solid tumors.
宿主免疫反应会影响癌症的生长、预后和对治疗的反应。在结直肠癌中,参与 T 细胞介导的适应性免疫的细胞的存在比当前的分期方法更好地预测生存率。我们使用最近与宿主免疫反应相关的基因表达(T(H1)-介导的适应性免疫、炎症和免疫抑制)对多个大型癌症标本队列进行层次聚类,以确定免疫相关基因表达是否导致肿瘤的临床显著分组。分析了前列腺癌(n=79)、乳腺癌(n=132)、肺癌(n=84)、多形性胶质母细胞瘤(n=120)和淋巴瘤(n=127)的微阵列数据。在腺癌中,T(H1)-介导的适应性免疫基因与更好的预后始终相关,而与炎症和免疫抑制相关的基因与结果的相关性则不同。具体来说,在年龄小于 45 岁的乳腺癌患者(p=0.04,风险比 [HR]=0.42)和前列腺癌患者(p=0.03,HR=0.36)中,T(H1)-介导的适应性免疫基因表达增加与预后良好相关,但在肺癌患者中则无相关性(p=0.45,HR=1.37)。在淋巴瘤中,表达炎症和免疫抑制基因增加的患者比表达 T(H1)-介导的适应性免疫基因的患者预后更好(p=0.01,HR=0.43),在多形性胶质母细胞瘤中,表达炎症基因比表达免疫抑制基因的患者预后更好(p=0.05,HR=0.62)。总体而言,表明免疫反应特定成分的基因表达特征在实体瘤中具有预后意义。