Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy.
Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy.
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DOI：
10.1053/j.gastro.2011.04.042
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发表时间：
2011-08
期刊：
影响因子：
29.4
通讯作者：
Tan P
中科院分区：
文献类型：
--
作者：
Tan IB;Ivanova T;Lim KH;Ong CW;Deng N;Lee J;Tan SH;Wu J;Lee MH;Ooi CH;Rha SY;Wong WK;Boussioutas A;Yeoh KG;So J;Yong WP;Tsuburaya A;Grabsch H;Toh HC;Rozen S;Cheong JH;Noh SH;Wan WK;Ajani JA;Lee JS;Tellez MS;Tan P
胃癌（GC）是一种异质性疾病，包括多种亚型，每种亚型在患者中具有不同的生物学特性和影响。我们试图通过对一大组GC细胞系的基因表达分析来鉴定GC的新的内在亚型。我们测试了这些亚型是否可能与患者生存时间和对各种标准治疗细胞毒性药物的反应差异有关。我们分析了37个GC细胞系的基因表达谱，以确定内在GC亚型。这些亚型在来自4个独立队列的521名患者的原发性肿瘤中得到验证，其中通过表达谱或亚型特异性免疫组织化学标记物（LGALS 4，CDH 17）确定亚型。还评估了对3种化疗药物（5-FU、顺铂、奥沙利铂）的体外敏感性。无监督细胞系分析鉴定了2种主要的内在基因组亚型（G-INT和G-DIF），它们具有不同的基因表达模式。基于多个患者队列的单变量和多变量分析，内在亚型（而不是基于Lauren组织病理学分类的亚型）是生存的预后因素。G-INT细胞系对5-FU和奥沙利铂的敏感性显著高于G-DIF细胞系，但对顺铂的耐药性更强。在患者中，内源性亚型与基于5-FU的辅助治疗后的生存时间相关。基于不同的表达模式，GC的内在亚型与患者的生存率和对化疗的反应相关。基于内在亚型的GC分类可用于确定预后和定制治疗。
Gastric cancer (GC) is a heterogeneous disease comprising multiple subtypes that each have distinct biological properties and effects in patients. We sought to identify new, intrinsic subtypes of GC by gene expression analysis of a large panel of GC cell lines. We tested if these subtypes might be associated with differences patient survival times and responses to various standard-of-care cytotoxic drugs. We analyzed gene expression profiles for 37 GC cell lines to identify intrinsic GC subtypes. These subtypes were validated in primary tumors from 521 patients in 4 independent cohorts, where the subtypes were determined by either expression profiling or subtype-specific immunohistochemical markers (LGALS4, CDH17). In vitro sensitivity to 3 chemotherapy drugs (5-FU, cisplatin, oxaliplatin) was also assessed. Unsupervised cell line analysis identified 2 major intrinsic genomic subtypes (G-INT and G-DIF), that had distinct patterns of gene expression. The intrinsic subtypes, but not subtypes based on Lauren’s histopathologic classification, were prognostic of survival, based on univariate and multivariate analysis in multiple patient cohorts. The G-INT cell lines were significantly more sensitive to 5-FU and oxaliplatin, but more resistant to cisplatin, than the G-DIF cell lines. In patients, intrinsic subtypes were associated with survival time following adjuvant, 5-FU based therapy. Intrinsic subtypes of GC, based on distinct patterns of expression, are associated with patient survival and response to chemotherapy. Classification of GC based on intrinsic subtypes might be used to determine prognosis and customize therapy.
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影响因子：
4.2
作者：
Hoshida Y;Toffanin S;Lachenmayer A;Villanueva A;Minguez B;Llovet JM
通讯作者：
Llovet JM
影响因子：
3
作者：
Huflejt, ME;Leffler, H
通讯作者：
Leffler, H
DOI：
10.1111/apm.1965.64.1.31
发表时间：
1965-01-01
期刊：
ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LAUREN, P
通讯作者：
LAUREN, P
DOI：
10.1016/s0140-6736(09)60617-6
发表时间：
2009-08-08
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hartgrink HH;Jansen EP;van Grieken NC;van de Velde CJ
通讯作者：
van de Velde CJ
影响因子：
29.4
作者：
Lee HJ;Nam KT;Park HS;Kim MA;Lafleur BJ;Aburatani H;Yang HK;Kim WH;Goldenring JR
通讯作者：
Goldenring JR