Department of General Surgery, Oregon Health & Science University, Portland, Oregon.
Pregon Health & Science University-Portland State University School of Public Health, Portland, Oregon.
Dis Colon Rectum. 2018 Nov;61(11):1290-1296. doi: 10.1097/DCR.0000000000001192.
MicroRNAs are dysregulated in colorectal cancer and subsets correlated with advanced tumor stage and metastasis. Data are lacking on microRNA dysregulation from early to late-stage disease.
The purpose of this study was to identify a microRNA signature associated with the primary tumor and metastatic site in stage IV disease and to examine whether the signature is evident in earlier stages.
A microRNA profile was generated and then explored in normal colon tissue (n = 5), early stage (stage I and II; n = 10), and late-stage (stage III and IV; n = 14) colorectal primary tumors via polymerase chain reaction to delineate molecular events that may promote colorectal carcinogenesis.
Genome-wide microRNA expression profiling was performed.
A total of 14 patient-matched stage IV primary colorectal cancer tumors and corresponding liver metastases were included.
MicroRNA array technology was used to identify microRNA expression-predictive metastatic potential in the primary tumor.
A distinct 9-member signature group of microRNAs was concurrent in stage IV primary colorectal cancer and their corresponding liver metastases, when compared with surrounding unaffected colon and liver tissue (microRNA-18b, microRNA-93, microRNA-182, microRNA-183, microRNA21, microRNA-486-5p, microRNA-500a, microRNA-552, and microRNA-941). Of the microRNA panel, only microRNA486-5p was differentially expressed in early stage colorectal cancer samples compared with normal tissue (p = 0.001) and additionally differentially expressed between late-stage colorectal cancer samples and normal tissue (p < 0.01).
Our microRNA profile was generated in a small subset of patients and will require validation in more samples.
We identified a distinct microRNA signature in primary colon and matched metastatic disease. On additional investigation, 1 microRNA was differentially expressed in both early and late-stage cancer patient samples, and it may herald an early event in colorectal carcinogenesis. This study warrants additional investigation with a larger patient cohort to better understand the effect of microRNAs in carcinogenesis. See Video Abstract at http://links.lww.com/DCR/A723.
在结直肠癌中，microRNAs 失调，其中一些与晚期肿瘤分期和转移相关。但在疾病的早期到晚期阶段，microRNAs 失调的数据仍然缺乏。
本研究旨在鉴定与 IV 期疾病原发性肿瘤和转移部位相关的 microRNA 特征，并研究该特征是否在早期阶段存在。
通过聚合酶链反应生成 microRNA 图谱，然后在正常结肠组织（n=5）、早期（I 期和 II 期；n=10）和晚期（III 期和 IV 期；n=14）结直肠原发性肿瘤中进行探索，以描绘可能促进结直肠癌发生的分子事件。
进行全基因组 microRNA 表达谱分析。
共纳入 14 例匹配的 IV 期原发性结直肠癌肿瘤及其相应的肝转移灶。
利用 microRNA 阵列技术鉴定原发性肿瘤中具有预测转移性潜力的 microRNA。
与周围未受影响的结肠和肝组织相比，IV 期原发性结直肠癌及其相应的肝转移灶中存在一个独特的 9 个 microRNA 特征群（microRNA-18b、microRNA-93、microRNA-182、microRNA-183、microRNA-21、microRNA-486-5p、microRNA-500a、microRNA-552 和 microRNA-941）。在 microRNA 面板中，只有 microRNA-486-5p 在早期结直肠癌样本中与正常组织存在差异表达（p=0.001），并且在晚期结直肠癌样本与正常组织之间也存在差异表达（p<0.01）。
我们的 microRNA 图谱是在一小部分患者中生成的，需要在更多的样本中进行验证。
我们在原发性结肠和匹配的转移性疾病中鉴定了一个独特的 microRNA 特征。进一步研究发现，1 个 microRNA 在早期和晚期癌症患者样本中均有差异表达，这可能预示了结直肠癌发生的早期事件。本研究需要进一步扩大患者队列进行研究，以更好地了解 microRNAs 在癌变中的作用。观看视频摘要，请访问 http://links.lww.com/DCR/A723。
