Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Department of Gastrointestinal Surgery, Hubei Key Laboratory of Tumor Biological Behaviors & Hubei Cancer Clinical Study Center, Wuhan Clinical Research Center for Peritoneal Carcinomatosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Anal Cell Pathol (Amst). 2019 Dec 16;2019:9740475. doi: 10.1155/2019/9740475. eCollection 2019.
Colorectal cancer (CRC) is one of the most frequent cancers occurring in developed countries. Distant CRC metastasis causes more than 90% of CRC-associated mortality. MicroRNAs (miRNAs) play a key role in regulating tumor metastasis and could be potential diagnostic biomarkers in CRC patients. This study is aimed at identifying miRNAs that can be used as diagnostic biomarkers for CRC metastasis. Towards this goal, we compared the expression of five miRNAs commonly associated with metastasis (i.e., miR-10b, miR-200c, miR-155, miR-21, and miR-31) between primary CRC (pCRC) tissues and corresponding metastatic lymph nodes (mCRC). Further, bioinformatics analysis of miR-31 was performed to predict target genes and related signaling pathways. Results showed that miR-31, miR-21, miR-10b, and miR-155 expression was increased to different extents, while miR-200c expression was lower in mCRC than that in pCRC. Moreover, we found that the level of both miR-31 and miR-21 was notably increased in pCRC when lymph node metastasis (LNM) was present, and the increase of miR-31 expression was more profound. Hence, upregulated miR-31 and miR-21 expression might be a miRNA signature in CRC metastasis. Moreover, we detected a higher miR-31 level in the plasma of CRC patients with LNM compared to patients without LNM or healthy individuals. With the bioinformatics analysis of miR-31, 121 putative target genes and transition of mitotic cell cycle and Wnt signaling pathway were identified to possibly play a role in CRC progression. We next identified seven hub genes via module analysis; of these, TNS1 was most likely to be the target of miR-31 and had significant prognostic value for CRC patients. In conclusion, miR-31 is significantly increased in the cancer tissues and plasma of CRC patients with LNM; thus, a high level of miR-31 in the plasma is a potential biomarker for the diagnosis of LNM of CRC.
结直肠癌(CRC)是发达国家最常见的癌症之一。CRC 的远处转移导致超过 90%的 CRC 相关死亡。微小 RNA(miRNA)在调节肿瘤转移中起着关键作用,并且可能是 CRC 患者的潜在诊断生物标志物。本研究旨在鉴定可作为 CRC 转移诊断生物标志物的 miRNA。为此,我们比较了 5 种常见转移相关 miRNA(miR-10b、miR-200c、miR-155、miR-21 和 miR-31)在原发性 CRC(pCRC)组织和相应转移性淋巴结(mCRC)之间的表达。进一步对 miR-31 进行了生物信息学分析,以预测靶基因和相关信号通路。结果表明,miR-31、miR-21、miR-10b 和 miR-155 的表达不同程度增加,而 miR-200c 在 mCRC 中的表达低于 pCRC。此外,我们发现当存在淋巴结转移(LNM)时,pCRC 中 miR-31 和 miR-21 的水平显著增加,并且 miR-31 的表达增加更为明显。因此,上调的 miR-31 和 miR-21 表达可能是 CRC 转移的 miRNA 特征。此外,我们在 LNM 患者的血浆中检测到比无 LNM 患者或健康个体更高的 miR-31 水平。通过 miR-31 的生物信息学分析,鉴定了 121 个可能的靶基因,并确定有丝分裂细胞周期和 Wnt 信号通路的转变可能在 CRC 进展中发挥作用。我们接下来通过模块分析鉴定了七个枢纽基因;其中,TNS1 最有可能是 miR-31 的靶基因,并且对 CRC 患者具有显著的预后价值。总之,miR-31 在 LNM 的 CRC 患者的肿瘤组织和血浆中显著增加;因此,血浆中高水平的 miR-31 可能是 CRC LNM 诊断的潜在生物标志物。