Colliver Daniel W, Crawford Nigel P S, Eichenberger Maurice R, Zacharius Wolfgang, Petras Robert E, Stromberg Arnold J, Galandiuk Susan
Digestive Surgery Research Laboratory, Price Institute for Surgical Research, Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Exp Mol Pathol. 2006 Feb;80(1):1-10. doi: 10.1016/j.yexmp.2005.09.008. Epub 2005 Nov 8.
Fundamental differences exist between ulcerative colitis (UC)-associated and sporadic forms of colorectal cancer, including preexisting inflammation, type of dysplasia, and timing of molecular events in carcinogenesis. Transcriptional alterations that occur in UC-associated neoplasia in the progression from normal mucosa through dysplastic epithelium to invasive cancer have not been described. We used Affymetrix U95Av2 microarrays to assess differential gene expression in the neoplastic progression of UC tissue from the colonic mucosa of individuals with benign UC, UC-dysplasia-associated lesions or masses, and UC adenocarcinoma. By correlating transcript alterations across tissue types using a mixed statistical model, we identified 699 genes exhibiting altered expression with dysplasia development. A different expression profile was observed in progression to adenocarcinoma with 392 transcripts exhibiting differential expression. There were 224 transcripts common to both dysplasia and adenocarcinoma. Most of the differentially expressed genes described herein were not previously known to play a role in neoplastic progression in UC, including transcripts affecting cell proliferation and apoptosis, signal transduction and signaling, and DNA repair. The altered expression of five transcripts was confirmed by quantitative real-time reverse-transcription polymerase chain reaction. Based on comparisons with previous studies on sporadic colorectal carcinoma, several similarities were found. There were, however, important differences that suggest that different molecular events may occur in the development of UC-associated neoplasia. Several of these genes demonstrated similar changes in dysplastic and cancerous tissue and may be involved in early cancer formation. Identification of these genes as potential clinical biomarkers may lead to improved early disease diagnosis.
溃疡性结肠炎（UC）相关型和散发性结直肠癌之间存在根本差异，包括先前存在的炎症、发育异常的类型以及致癌过程中分子事件的发生时间。从正常黏膜经发育异常上皮到浸润性癌的UC相关肿瘤形成过程中发生的转录改变尚未见报道。我们使用Affymetrix U95Av2微阵列评估来自患有良性UC、UC发育异常相关病变或肿块以及UC腺癌个体的结肠黏膜中UC组织肿瘤进展过程中的差异基因表达。通过使用混合统计模型关联不同组织类型的转录本改变，我们鉴定出699个随着发育异常发展而表达改变的基因。在进展为腺癌的过程中观察到不同的表达谱，有392个转录本表现出差异表达。发育异常和腺癌中共有224个转录本。本文描述的大多数差异表达基因以前并不知晓在UC肿瘤进展中起作用，包括影响细胞增殖和凋亡、信号转导以及DNA修复的转录本。通过定量实时逆转录聚合酶链反应证实了五个转录本的表达改变。基于与先前散发性结直肠癌研究的比较，发现了一些相似之处。然而，也存在重要差异，这表明在UC相关肿瘤形成过程中可能发生不同分子事件。其中一些基因在发育异常和癌组织中表现出相似变化，可能参与早期癌症形成。将这些基因鉴定为潜在临床生物标志物可能会改善疾病早期诊断。
