Žlajpah Margareta, Boštjančič Emanuela, Tepeš Bojan, Zidar Nina
Faculty of Medicine, Institute of Pathology, University of Ljubljana, 1000 Ljubljana, Slovenia.
Gastroenterology Unit, AM DC Rogaška, 3250 Rogaška Slatina, Slovenia.
Cancers (Basel). 2020 Dec 11;12(12):3715. doi: 10.3390/cancers12123715.
Colorectal carcinoma usually evolves gradually, forming a spectrum of lesions, due to accumulation of genetic mutations and epigenetic alterations. Many early lesions are detected since the introduction of screening programs. The greatest challenge is to distinguish between adenomas with epithelial misplacement (AEM) and adenomas with early carcinoma (AEC), considering the diagnosis affects prognosis and treatment. We analyzed the expression of selected extracellular matrix (ECM)-related genes and proteins, and their regulatory microRNAs using RT-qPCR and immunohistochemistry in biopsies from 44 patients. Differences were observed in AEM in comparison to AEC for , , , , and , reflecting inflammatory stromal reaction to traumatisation and misplacement of dysplastic glands in the submucosa in the former, and desmoplastic stromal reaction to true invasion of dysplastic glands in the submucosa in the latter. Expression of regulatory microRNAs and significantly negatively correlated with the expression of their regulated genes, while significant difference between AEM and AEC was observed only for . The described expression patterns are too complex to be used in diagnostic work, but might contribute to better understanding ECM changes in colorectal carcinoma development, helping to find new markers in the future.
由于基因突变和表观遗传改变的积累,结直肠癌通常会逐渐发展,形成一系列病变。自引入筛查计划以来,许多早期病变得以被检测到。最大的挑战在于区分上皮错位腺瘤(AEM)和早期癌腺瘤(AEC),因为诊断会影响预后和治疗。我们使用逆转录定量聚合酶链反应(RT-qPCR)和免疫组织化学分析了44例患者活检组织中选定的细胞外基质(ECM)相关基因和蛋白质及其调控微小RNA的表达。与AEC相比,在AEM中观察到了[具体基因或蛋白质名称1]、[具体基因或蛋白质名称2]、[具体基因或蛋白质名称3]、[具体基因或蛋白质名称4]和[具体基因或蛋白质名称5]的差异,这反映了前者中发育异常腺体在黏膜下层的创伤和错位引发的炎症性基质反应,以及后者中发育异常腺体对黏膜下层真正浸润引发的促纤维增生性基质反应。调控微小RNA[具体微小RNA名称1]和[具体微小RNA名称2]的表达与其调控基因的表达显著负相关,而仅在[具体基因或蛋白质名称3]方面观察到AEM和AEC之间存在显著差异。所描述的表达模式过于复杂,无法用于诊断工作,但可能有助于更好地理解结直肠癌发展过程中的ECM变化,为未来寻找新的标志物提供帮助。