Li Qian, Li Nanshan, Lao Yueqiong, Lin Wu, Jiang Guojun, Wei Nan, Wang Canghai, Liu Kuiliang, Wu Jing
Department of Gastroenterology, Peking University Ninth School of Clinical Medicine, Beijing, 100038, China.
Department of Gastroenterology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
Dig Dis Sci. 2017 May;62(5):1235-1245. doi: 10.1007/s10620-017-4465-6. Epub 2017 Feb 3.
Long noncoding RNAs (lncRNAs) have been suggested to be biomarkers for diagnosis and prognosis of sporadic colorectal cancer.
This study aimed to characterize the expression profile of lncRNAs in DNA mismatch repair-proficient (pMMR) early-stage colon cancer (CC).
The microsatellite instability (MSI) status was examined by a multiplex PCR. The expression of lncRNA and mRNA was analyzed by microarrays. The differentially expressed lncRNAs and mRNAs were determined by bioinformatic analyses and validated in 44 CC samples and 32 non-tumor colonic specimens by quantitative real-time polymerase chain reaction (qRT-PCR).
We found that 16 out of 67 CC had MSI-L CC and 7 with MSI-H. In comparison with that in five non-tumor colonic samples, microarray indicated that 1492 lncRNAs and 1639 mRNAs were upregulated while 1804 lncRNAs and 1073 mRNAs downregulated in four pMMR early-stage CC. Bioinformatic analyses revealed that the differentially expressed mRNAs were involved in the process of cell division, angiogenesis, apoptotic, differentiation, the PI3K-Akt/p53/TNF pathways and others. The co-expression lncRNA and mRNA networks indicated five hot spots with significantly high co-expression degrees. Further quantitative RT-PCR revealed that 4 out of 6 lncRNAs were significantly upregulated while the other 2 lncRNAs were downregulated in the CC. Stratification analysis demonstrated that 5 out of 6 lncRNAs were significantly associated with TNM stage and/or distant metastasis in this population.
Differentially expressed lncRNAs were significantly associated with clinical features of patients with pMMR CC and may participate in the tumorigenesis of pMMR CC.
长链非编码RNA（lncRNAs）被认为是散发性结直肠癌诊断和预后的生物标志物。
本研究旨在表征DNA错配修复功能正常（pMMR）的早期结肠癌（CC）中lncRNAs的表达谱。
通过多重PCR检测微卫星不稳定性（MSI）状态。通过微阵列分析lncRNA和mRNA的表达。通过生物信息学分析确定差异表达的lncRNAs和mRNAs，并通过定量实时聚合酶链反应（qRT-PCR）在44例CC样本和32例非肿瘤结肠标本中进行验证。
我们发现67例CC中有16例为微卫星低度不稳定（MSI-L）CC，7例为微卫星高度不稳定（MSI-H）。与5例非肿瘤结肠样本相比，微阵列显示在4例pMMR早期CC中，1492个lncRNAs和1639个mRNAs上调，而1804个lncRNAs和1073个mRNAs下调。生物信息学分析显示，差异表达的mRNAs参与细胞分裂、血管生成、凋亡、分化、PI3K-Akt/p53/TNF等途径。共表达lncRNA和mRNA网络显示出5个共表达度显著较高的热点。进一步的定量RT-PCR显示，6个lncRNAs中有4个在CC中显著上调，而其他2个lncRNAs下调。分层分析表明，该人群中6个lncRNAs中有5个与TNM分期和/或远处转移显著相关。
差异表达的lncRNAs与pMMR CC患者的临床特征显著相关，可能参与pMMR CC的肿瘤发生。
