D'Errico Mariarosaria, de Rinaldis Emanuele, Blasi Monica F, Viti Valentina, Falchetti Mario, Calcagnile Angelo, Sera Francesco, Saieva Calogero, Ottini Laura, Palli Domenico, Palombo Fabio, Giuliani Alessandro, Dogliotti Eugenia
Department of Environment and Primary Prevention, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Eur J Cancer. 2009 Feb;45(3):461-9. doi: 10.1016/j.ejca.2008.10.032. Epub 2008 Dec 8.
Gastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed. Unsupervised analysis showed that the immune and apoptotic gene networks efficiently discriminated these two cancer types. Hierarchical clustering analysis revealed numerous gene expression changes associated with the MSI phenotype. Amongst these, the p53-responsive genes maspin and 14-3-3 sigma were significantly more expressed in tumours with than without MSI. A tight immunosurveillance coupled with a functional p53 gene response is consistent with the better prognosis of MSI cancers. Frequent silencing of MLH1 and downregulation of MMR target genes, such as MRE11 and MBD4, characterised MSI tumours. The downregulation of SMUG1 was also a typical feature of these tumours. The DNA repair gene expression profile of gastric cancer with MSI is of relevance for therapy response.
错配修复（MMR）失活的胃癌具有微卫星不稳定性（MSI）的特征。在本研究中，分析了38例有或无MSI的胃癌的转录谱。无监督分析表明，免疫和凋亡基因网络能有效区分这两种癌症类型。层次聚类分析揭示了许多与MSI表型相关的基因表达变化。其中，p53反应基因maspin和14-3-3 sigma在有MSI的肿瘤中比无MSI的肿瘤中表达明显更高。紧密的免疫监视与功能性p53基因反应与MSI癌症较好的预后一致。MSI肿瘤的特征是MLH1频繁沉默以及MMR靶基因（如MRE11和MBD4）下调。SMUG1下调也是这些肿瘤的典型特征。具有MSI的胃癌的DNA修复基因表达谱与治疗反应相关。
