背景:尽管新的筛查策略和药物疗法的进步,家族性腺瘤性息肉病(FAP)的癌变率稳定,甚至在最近几年增加。因此,它需要更多的研究来表征和理解FAP的潜在机制。
目的:确定驱动家族性腺瘤性息肉病(FAP)发病的基因。
方法:我们对队列(GSE111156)基因图谱进行了研究,由四组基因表达组成(癌症的基因表达,FAP患者十二指肠癌的腺瘤和正常组织被定义为病例N,案例A和案例C,而来自没有十二指肠癌的FAP患者的腺瘤组织为CtrlA)。应用追踪肿瘤免疫表型(TIP)网站来揭示FAP的免疫浸润谱和特征基因。我们将关键模块(粉红色和午夜模块)的基因与特征基因进行合并,以获得与FAP发病机制相关的生物标志物。用定量实时聚合酶链反应(qRT-PCR)检测FAP肿瘤内区域(IT)和肿瘤边缘(TR)中这5种生物标志物的表达。
结果:总计,在案例C中确定了220、23和63个DEG,A和N,与CtrlA相比,总的来说,在案例C和A中确定了196和10个DEG,分开,与病例N相比,共有四种生物标志物,包括CCL5、CD3G、最终确定CD2和TLR3与粉红色模块相关,而仅鉴定出一种与午夜模块相关的生物标志物(KLF2)。利用qRT-PCR,FAPIT组织中所有生物标志物均明显升高。
结论:我们确定了FAP发病机制的五种潜在生物标志物,以了解FAP进展的基本机制,并揭示了FAP诊断或治疗的一些可能靶标。
UNASSIGNED: Despite the advancement of new screening strategies and the advances in pharmacological therapies, the cancerization rates of familial adenomatous polyposis (FAP) are stable and even increased in the last years. Therefore, it necessitates additional research to characterize and understand the underlying mechanisms of FAP.
UNASSIGNED: To determine the genes that drive the pathogenesis of familial adenomatous polyposis (FAP).
UNASSIGNED: We performed on a cohort (GSE111156) gene profile, which consist of four group of gene expressions (the gene expressions of cancer, adenoma and normal tissue of duodenal cancer from patients with FAP were defined as Case N, Case A and Case C respectively, while that of adenoma tissue from patients with FAP who did not have duodenal cancer was Ctrl A). Tracking Tumor Immunophenotype (TIP) website was applied to reveal immune infiltration profile and signature genes of FAP. We merged the genes of key module (pink and midnight module) with signature genes to obtained the biomarkers related with FAP pathogenesis. The expression of these five biomarkers in FAP intratumoral region (IT) and tumor rim (TR) was detected with Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR).
UNASSIGNED: In total, 220, 23 and 63 DEGs were determined in Cases C, A and N, in comparison to Ctrl A. In total, 196 and 10 DEGs were determined in Cases C and A, separately, as compared to Case N. A total of four biomarkers including CCL5, CD3G, CD2 and TLR3 were finally identified associated with pink module, while only one biomarker (KLF2) associated with midnight module was identified. All biomarkers were evidently raised in FAP IT tissues utilizing qRT-PCR.
UNASSIGNED: We identified five potential biomarkers for pathogenesis of FAP to understand the fundamental mechanisms of FAP progression and revealed some probable targets for the diagnosis or treatment of FAP.