背景:对于结直肠癌(CRC)尚无有效的早期诊断生物标志物。因此,我们试图鉴定新的生物标志物,这些生物标志物可以将CRC从癌前病变发展为侵袭性形式.最近的研究表明,microRNA(miRs)与癌症侵袭和进展的发生有关。
目的:我们假设鉴定与CRC相关的miRs可能有助于在早期阶段检测这种疾病。
方法:我们对79个孤立的结直肠肿瘤进行了综合分析,包括腺瘤,粘膜内癌,以及使用GeneChipmiRNA4.0微阵列分析显示微卫星稳定表型的侵袭性CRC。我们检查的结直肠肿瘤分为2组(第一组42和第二组37)。
结果:首先,进行聚类分析以根据以下标准对多个miR的表达模式进行分层:表达的倍数变化(<-2.0或>2.0),p<0.05,并且成熟miRs。因此,合并miRs的表达模式被细分为与肿瘤分级相关的3个亚组.每个亚组的特征在于特异性miRs。此外,我们发现特定的miRs,包括miR-140-3p和miR-378i,与癌症侵袭密切相关。最后,我们分析了同一肿瘤中存在的腺瘤和癌成分之间的成对失调的miRs.
结论:我们发现,在从腺瘤到粘膜内癌的进展过程中,一些miRs失调。特异性miR可能在从粘膜内肿瘤到侵袭性CRC的进展中具有关键作用。
No effective early diagnostic biomarkers are available for colorectal cancer (CRC). Therefore, we sought to identify new biomarkers that could identify CRC from progression as a pre-cancerous lesion to its invasive form. Recent studies have shown that microRNAs (miRs) are associated with the onset of cancer invasion and progression.
We hypothesized that the identification of miRs associated with CRC might be useful to detect this disease at early stages.
We conducted an integrated analysis of 79 isolated colorectal tumor glands, including adenomas, intramucosal cancers, and invasive CRCs that showed a microsatellite stable phenotype using GeneChip miRNA 4.0 microarray assays. The colorectal tumors we examined were divided into 2 cohorts (42 in the first cohort and 37 in the second cohort).
First, cluster analysis was performed to stratify expression patterns of multiple miRs that were pooled according to the following criteria: fold change in expression (< -2.0 or > 2.0), p < 0.05, and mature miRs. As a result, the expression patterns of pooled miRs were subdivided into 3 subgroups that were correlated with tumor grade. Each subgroup was characterized by specific miRs. In addition, we found that specific miRs, including miR-140-3p and miR-378i, were closely associated with cancer invasion. Finally, we analyzed paired dysregulated miRs between adenomatous and cancerous components present within the same tumor.
We showed that several miRs were dysregulated during progression from adenoma to intramucosal cancer. Specific miRs may have key roles in progression from intramucosal tumor to invasive CRC.