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首页> 美国卫生研究院文献>Wiley-Blackwell Online Open >Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal‐type gastric cancer tumorigenesis
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Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal‐type gastric cancer tumorigenesis

机译：解剖胃癌前病变和早期胃癌的表达谱以探索肠型胃癌肿瘤发生中的关键分子

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Intestinal‐type gastric cancer (IGC) has a clear and multistep histological evolution. No studies have comprehensively explored gastric tumorigenesis from inflammation through low‐grade intraepithelial neoplasia (LGIN) and high‐grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC). We sought to investigate the characteristics participating in IGC tumorigenesis and identify related prognostic information within the process. RNA expression profiles of 94 gastroscopic biopsies from 47 patients, including gastric precancerous lesions (GPL: LGIN and HGIN), EGC, and paired controls, were detected by Agilent Microarray. During IGC tumorigenesis from LGIN through HGIN to EGC, the number of activity‐changed tumor hallmarks increased. LGIN and HGIN had similar expression profiles when compared to EGC. We observed an increase in the stemness of gastric epithelial cells in LGIN, HGIN, and EGC, and we found 27 consistent genes that might contribute to dedifferentiation, including five driver genes. Remarkably, we perceived that the immune microenvironment was more active in EGC than in GPL, especially in the infiltration of lymphocytes and macrophages. We identified a five‐gene signature from the gastric tumorigenesis process that could independently predict the overall survival and disease‐free survival of GC patients (log‐rank test:  n > 300) and by comparing with two established prognostic signatures in GC. In conclusion, during IGC tumorigenesis, cancer‐like changes occur in LGIN and accumulate in HGIN and EGC. The immune microenvironment is more active in EGC than in LGIN and HGIN. The identified signature from the tumorigenesis process has robust prognostic significance for GC patients. © 2020 The Authors. published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
机译：肠型胃癌（IGC）具有清晰且多步骤的组织学演变。从炎症到低度上皮内瘤变（LGIN）和高级别上皮内瘤变（HGIN）到早期胃癌（EGC）的炎症，尚无关于胃癌发生的研究的全面研究。我们试图调查参与IGC肿瘤发生的特征，并在该过程中确定相关的预后信息。通过安捷伦微阵列检测了来自47例患者的94例胃镜活检的RNA表达谱，包括胃癌前病变（GPL：LGIN和HGIN），EGC和配对对照。在从LGIN到HGIN到EGC的IGC肿瘤发生过程中，活动改变的肿瘤标志物数量增加。与EGC相比，LGIN和HGIN具有相似的表达谱。我们观察到LGIN，HGIN和EGC中胃上皮细胞的干细胞增加，并且发现了27个可能导致去分化的一致基因，包括5个驱动基因。值得注意的是，我们认为免疫微环境在EGC中比在GPL中更为活跃，尤其是在淋巴细胞和巨噬细胞浸润中。我们从胃癌发生过程中鉴定出五基因签名，可以独立预测GC患者的总体生存率和无病生存率（对数秩检验：rankn> 300），并与两个已建立的预后签名进行比较。总之，在IGC发生肿瘤的过程中，LGIN中会发生类似癌的变化，并在HGIN和EGC中积累。 EGC中的免疫微环境比LGIN和HGIN更活跃。从肿瘤发生过程中鉴定出的特征对GC患者具有强大的预后意义。 ©2020作者。由John Wiley＆Sons Ltd代表大不列颠及爱尔兰病理学会出版。

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