PDF(Pubmed)
Abstract：
Early onset colorectal cancer (EOCRC) rates have increased in recent decades. While lowering the recommended age for routine colonoscopies to 45 may reduce this burden, such measures do not address those who develop CRC before that age. Additional measures are needed to identify individuals at-risk for CRC. To better define transcriptomic events that precede the development of CRC, we performed RNA-sequencing analysis in colon organoids derived from seven healthy and six familial adenomatous polyposis (FAP) patients. This led to the identification of 2635 significant differentially expressed genes (FDR < 0.05). Through secondary analysis of publicly available datasets, we found that these genes were enriched for significant genes also present in FAP CRC and non-hereditary CRC datasets, including a subset that were unique to EOCRC. By exposing FAP colon organoids to a three-day ethanol treatment, we found that two EOCRC-relevant genes were also targets of CRC related lifestyle factors. Our data provides unique insight into the potential, early mechanisms of CRC development in colon epithelial cells, which may provide biomarkers for patient monitoring. We also show how modifiable lifestyle factors may further alter genes relevant to EOCRC, adding weight to the hypothesis that such factors represent an important contributor to increased EOCRC incidence.
摘要：
近几十年来，早发性结直肠癌（EOCRC）的发病率有所增加。虽然将常规结肠镜检查的推荐年龄降低到45岁可能会减轻这种负担，这些措施不适用于在该年龄之前发展儿童权利公约的人。需要采取其他措施来确定面临CRC风险的个人。为了更好地定义在CRC发生之前的转录组事件，我们对来自7例健康和6例家族性腺瘤性息肉病(FAP)患者的结肠类器官进行了RNA测序分析.这导致鉴定了2635个显著差异表达的基因(FDR<0.05)。通过对公开数据集的二次分析，我们发现这些基因富含FAPCRC和非遗传性CRC数据集中的重要基因，包括EOCRC特有的子集。通过将FAP结肠类器官暴露于为期三天的乙醇处理，我们发现两个EOCRC相关基因也是CRC相关生活方式因素的靶标.我们的数据提供了对潜力的独特见解，结肠上皮细胞发生CRC的早期机制，可以为患者监测提供生物标志物。我们还展示了可改变的生活方式因素如何进一步改变与EOCRC相关的基因，增加了以下假设的权重：这些因素是导致EOCRC发病率增加的重要因素。
