Colorectal cancers with microsatellite instability display mRNA expression signatures characteristic of increased immunogenicity.
Colorectal cancers with microsatellite instability display mRNA expression signatures characteristic of increased immunogenicity.
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DOI：
10.1186/1476-4598-3-21
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发表时间：
2004-08-06
期刊：
影响因子：
37.3
通讯作者：
Dorudi S
中科院分区：
文献类型：
--
作者：
Banerjea A;Ahmed S;Hands RE;Huang F;Han X;Shaw PM;Feakins R;Bustin SA;Dorudi S
与微卫星稳定（MSS）癌症相比，显示高度微卫星不稳定（MSI-H）的结直肠癌具有改善的预后。观察到明显的淋巴细胞浸润表明MSI-H癌症固有地更具免疫原性。我们的目的是比较MSI-H和MSS癌症的基因表达谱，为前者的激活免疫反应提供证据。我们分析了133例结直肠癌患者的组织，这些患者完全同意并获得当地伦理委员会的批准。分析BAT-26基因组DNA的微卫星不稳定性。将高质量RNA用于Affyiiffi® HG-U133A芯片上的微阵列分析。在GeneSpring软件版本6.0上分析数据。对28例MSI-H和26例MSS癌进行了特异性实时RT-PCR。比较29例MSI-H和104例MSS癌症，确定了两组之间差异表达的2070个基因[P <0.005]。值得注意的是，许多关键的免疫调节基因在MSI-H癌症中上调。这些包括抗原伴侣分子（HSP-70、HSP-110、钙网蛋白、gp96）、促炎细胞因子（白介素（IL）-18、IL-15、IL-8、IL-24、IL-7）和细胞毒性介质（颗粒溶素、颗粒酶A）。定量RT-PCR证实HSP-70 [P = 0.016]、HSP-110 [P = 0.002]、IL-18 [P = 0.004]、IL-8 [0.002]和Granulysin [P <0.0001]表达上调。与免疫反应有关的大量基因的上调支持了MSI-H癌症具有免疫原性的理论。MSI-H癌症中热休克蛋白上调的新观察结果鉴于这些蛋白在先天性和抗原特异性免疫原性中的公认作用是非常重要的。促炎细胞因子和细胞毒性介质的mRNA水平增加也表明激活的抗肿瘤免疫应答。
Colorectal cancers displaying high-degree microsatellite instability (MSI-H) have an improved prognosis compared to microsatellite stable (MSS) cancers. The observation of pronounced lymphocytic infiltrates suggests that MSI-H cancers are inherently more immunogenic. We aimed to compare the gene expression profiles of MSI-H and MSS cancers to provide evidence for an activated immune response in the former. We analysed tissue from 133 colorectal cancer patients with full consent and Local Ethics Committee approval. Genomic DNA was analysed for microsatellite instability in BAT-26. High-quality RNA was used for microarray analysis on the Affymetrix® HG-U133A chip. Data was analysed on GeneSpring software version 6.0. Confirmatory real-time RT-PCR was performed on 28 MSI-H and 26 MSS cancers. A comparison of 29 MSI-H and 104 MSS cancers identified 2070 genes that were differentially expressed between the two groups [P < 0.005]. Significantly, many key immunomodulatory genes were up-regulated in MSI-H cancers. These included antigen chaperone molecules (HSP-70, HSP-110, Calreticulin, gp96), pro-inflammatory cytokines (Interleukin (IL)-18, IL-15, IL-8, IL-24, IL-7) and cytotoxic mediators (Granulysin, Granzyme A). Quantitative RT-PCR confirmed up-regulation of HSP-70 [P = 0.016], HSP-110 [P = 0.002], IL-18 [P = 0.004], IL-8 [0.002] and Granulysin [P < 0.0001]. The upregulation of a large number of genes implicated in immune response supports the theory that MSI-H cancers are immunogenic. The novel observation of Heat Shock Protein up-regulation in MSI-H cancer is highly significant in light of the recognised roles of these proteins in innate and antigen-specific immunogenicity. Increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators also indicate an activated anti-tumour immune response.
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DOI：
10.1073/pnas.231326898
发表时间：
2001-11-06
影响因子：
11.1
作者：
Saeterdal, I;Bjorheim, J;Gaudernack, G
通讯作者：
Gaudernack, G
DOI：
10.1016/s0003-3995(02)01115-2
发表时间：
2002-04-01
期刊：
ANNALES DE GENETIQUE
影响因子：
--
作者：
Duval, A;Hamelin, R
通讯作者：
Hamelin, R
影响因子：
8.8
作者：
Lovig, T;Andersen, S N;Thorstensen, L;Diep, C B;Meling, G I;Lothe, R A;Rognum, T O
通讯作者：
Rognum, T O
影响因子：
158.5
作者：
Gryfe, R;Kim, H;Gallinger, S
通讯作者：
Gallinger, S
影响因子：
6.1
作者：
Zhang, XS;Chen, ZA;Xiang, J
通讯作者：
Xiang, J