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全基因组 mRNA 表达分析鉴定三叶因子 1 参与了无蒂锯齿状病变的发展。

Genome-wide analysis of mRNA expression identified the involvement of trefoil factor 1 in the development of sessile serrated lesions.

机构信息

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou 028-3695, Japan.

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Shiwagun, Yahabachou 028-3695, Japan.

出版信息

Pathol Res Pract. 2022 Aug;236:153987. doi: 10.1016/j.prp.2022.153987. Epub 2022 Jun 18.

Abstract

Precursor lesions that progress into colorectal cancer (CRC) could be largely classified into sessile serrated lesions (SSLs), traditional serrated adenoma (TSA), and tubular adenoma (TA). We aimed to determine whether high expression of trefoil factor 1 (TFF1) is closely associated with serrated lesions, particularly SSLs. The samples were divided into the first (12 SSLs, 5 TSAs, and 15 TAs) and second cohorts (15 SSLs, 9 TSAs, and 15 TAs). First, we investigated TFF1 expression in isolated gland samples using array-based and reverse-transcription PCR. Second, we performed immunohistochemical analysis of TFF1 expression in paraffin-embedded tissues obtained from SSL, TSA, TA, and hyperplastic polyp (HP) samples. In addition, we compared TFF1 mRNA levels between SSLs and HPs. TFF1 expression was significantly higher in SSLs than in TSA and TA in both cohorts. Additionally, immunohistochemical staining of TFF1 in the HP, SSL, TSA, and TA samples revealed significant differences in the immunohistochemical scores of TFF1 among the four types of lesions (higher expression in SSLs than in the other three lesions). Finally, there were significant differences in TFF1 mRNA expression levels between SSLs and HPs in paraffin-embedded tissues. However, there was considerable overlap in the immunohistochemical scores and expression levels of TFF1 transcripts between SSLs and HPs. The current findings may help elucidate the molecular mechanisms involved in serrated lesion development. In addition, we suggest that despite the limited practical application, upregulation of TFF1 transcripts may help differentiate SSLs from other lesions.

摘要

进展为结直肠癌(CRC)的癌前病变可大致分为无蒂锯齿状病变(SSLs)、传统锯齿状腺瘤(TSA)和管状腺瘤(TA)。我们旨在确定三叶因子 1(TFF1)的高表达是否与锯齿状病变,特别是 SSLs 密切相关。样本分为第一队列(12 个 SSLs、5 个 TSAs 和 15 个 TAs)和第二队列(15 个 SSLs、9 个 TSAs 和 15 个 TAs)。首先,我们使用基于阵列和逆转录 PCR 研究了分离腺样本中的 TFF1 表达。其次,我们对 SSL、TSA、TA 和增生性息肉(HP)样本中的 TFF1 表达进行了石蜡包埋组织的免疫组织化学分析。此外,我们比较了 SSLs 和 HPs 之间的 TFF1 mRNA 水平。在两个队列中,SSLs 中的 TFF1 表达明显高于 TSA 和 TA。此外,HP、SSL、TSA 和 TA 样本中 TFF1 的免疫组织化学染色显示,四种病变之间的 TFF1 免疫组织化学评分存在显著差异(SSLs 中表达更高)。最后,在石蜡包埋组织中,SSLs 和 HPs 之间的 TFF1 mRNA 表达水平存在显著差异。然而,SSLs 和 HPs 之间 TFF1 转录本的免疫组织化学评分和表达水平存在相当大的重叠。目前的研究结果可能有助于阐明锯齿状病变发展中涉及的分子机制。此外,我们建议尽管实际应用有限,但 TFF1 转录本的上调可能有助于将 SSLs 与其他病变区分开来。

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