Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions.
Gene signature distinguishes patients with chronic ulcerative colitis harboring remote neoplastic lesions.
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DOI：
10.1097/mib.0b013e3182802bac
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发表时间：
2013-03
影响因子：
4.9
通讯作者：
Bissonnette M
中科院分区：
文献类型：
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作者：
Pekow J;Dougherty U;Huang Y;Gometz E;Nathanson J;Cohen G;Levy S;Kocherginsky M;Venu N;Westerhoff M;Hart J;Noffsinger AE;Hanauer SB;Hurst RD;Fichera A;Joseph LJ;Liu Q;Bissonnette M
溃疡性结肠炎(UC)患者患结直肠癌的风险增加。结肠镜检查UC肿瘤的标准方法是侵袭性的，可能会漏掉扁平病变。我们试图在没有活动性炎症的非发育不良粘膜中确定一个基因表达特征，作为远处肿瘤性病变的标志。应用基因芯片技术对5例正常对照、4例非典型增生UC患者和11例远处肿瘤UC患者的基因表达进行分析。确定了显著差异表达基因的共同基因本体论途径。用实时荧光定量聚合酶链式反应(Real Time PCR)检测从对照组到无肿瘤的UC、到有远处肿瘤的UC中逐渐显著上调的基因的表达。用免疫组织化学方法检测了几种基因产物。UC伴瘤变组中468个基因表达显著上调，541个基因表达显著下调。9个基因(ACSL1、BIRC3、CLC、CREM、ELTD1、FGG、S100A9、THBD和TPD52L1)从对照组到非发育不良UC再到UC伴肿瘤，表达逐渐显著上调。免疫组织化学染色显示S100A9和REG1α在UC相关癌和UC远处肿瘤患者的非异型增生组织中的表达高于UC非肿瘤患者和对照组。慢性UC患者远端结肠的基因表达变化是场效应，可识别存在远处肿瘤损害的患者。这些标志物可能会导致一种更准确、侵入性更小的方法来检测炎症性肠病患者的肿瘤。
Individuals with ulcerative colitis (UC) are at increased risk for colorectal cancer. The standard method of surveillance for neoplasia in UC by colonoscopy is invasive and can miss flat lesions. We sought to identify a gene expression signature in non-dysplastic mucosa without active inflammation that could serve as a marker for remote neoplastic lesions. Gene expression was analyzed by cDNA microarray in 5 normal controls, 4 UC patients without dysplasia, and 11 UC patients harboring remote neoplasia. Common gene ontology pathways of significantly differentially expressed genes were identified. Expression of genes which were progressively and significantly up-regulated from controls, to UC without neoplasia, to UC with remote neoplasia were evaluated by real time PCR. Several gene products were also examined by immunohistochemistry. 468 genes were significantly up-regulated and 541 genes were significantly down-regulated in UC patints with neoplasia compared to UC patients without neoplasia. Nine genes (ACSL1, BIRC3, CLC, CREM, ELTD1, FGG, S100A9, THBD, and TPD52L1) were progressively and significantly up-regulated from controls to non-dysplastic UC to UC with neoplasia. Immunostaining of proteins revealed increased expression of S100A9 and REG1α in UC-associated cancer and in non-dysplastic tissue from UC patients harboring remote neoplasia, compared to UC patients without neoplasia and controls. Gene expression changes occurring as a field effect in the distal colon of patients with chronic UC identify patients harboring remote neoplastic lesions. These markers may lead to a more accurate and less invasive method of detection of neoplasia in patients with inflammatory bowel disease.