Infrequently expressed miRNAs influence survival after diagnosis with colorectal cancer.
Infrequently expressed miRNAs influence survival after diagnosis with colorectal cancer.
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DOI：
10.18632/oncotarget.19863
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发表时间：
2017-10-13
期刊：
影响因子：
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通讯作者：
Mullany LE
中科院分区：
文献类型：
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作者：
Slattery ML;Pellatt AJ;Lee FY;Herrick JS;Samowitz WS;Stevens JR;Wolff RK;Mullany LE
在结直肠组织中表达的mirna中有一半的表达率< 50%。许多不常表达的mirna表达水平较低。我们假设，当表达频率较低的mirna水平较高时，会影响结直肠癌（CRC）诊断后的疾病分期和生存；低水平的表达可能是背景噪音。我们在1893例以人群为基础的结直肠癌病例中检测了304种不常表达的miRNA，这些病例具有配对的癌和正常粘膜miRNA谱。在调整了年龄、研究中心、性别、MSI状态和AJCC分期后，我们评估了mirna与疾病分期和生存率的关系。利用RNA-Seq数据对这些miRNA进行进一步评估，以确定miRNA::mRNA的关联，这可能有助于了解miRNA的功能。在结肠癌患者中，11种mirna与疾病晚期相关（Q值= 0.10）。8种不常表达的mirna如果在总体结直肠癌中高表达，则会影响生存。其中，如果它们高表达，即miR-124-3p， miR-143-5p, miR-145-3p， miR31-5p和miR-99b-5p，则有5种高表达与更好的生存率相关，即miR-362-5p， miR-374a-5p和miR-590-5p。在结肠特异性癌组织中不常表达的13种mirna如果高表达，则与结直肠癌存活相关。对miRNA的评估：mRNA关联表明，受不常表达的miRNA影响的mRNA表达有助于形成影响疾病进展和预后的网络和途径。我们的大型研究使我们能够在去除背景噪声后检查不频繁表达的mirna的含义。这些结果需要在其他研究中得到验证。在其他研究中证实我们的发现可能成为预后的重要标志。
Half of miRNAs expressed in colorectal tissue are expressed < 50% of the population. Many infrequently expressed miRNAs have low levels of expression. We hypothesize that less frequently expressed miRNAs, when expressed at higher levels, influence both disease stage and survival after diagnosis with colorectal cancer (CRC); low levels of expression may be background noise. We examine 304 infrequently expressed miRNAs in 1893 population-based cases of CRC with paired carcinoma and normal mucosa miRNA profiles. We evaluate miRNAs with disease stage and survival after adjusting for age, study center, sex, MSI status, and AJCC stage. These miRNAs were further evaluated with RNA-Seq data to identify miRNA::mRNA associations that may provide insight into the functionality of miRNAs. Eleven miRNAs were associated with advanced disease stage among colon cancer patients (Q value = 0.10). Eight infrequently expressed miRNAs influenced survival if highly expressed in overall CRC. Of these, five increased likelihood of dying if they were highly expressed, i.e. miR-124-3p, miR-143-5p, miR-145-3p, miR31-5p, and miR-99b-5p, while three were associated with better survival if highly expressed, i.e. miR-362-5p, miR-374a-5p, and miR-590-5p. Thirteen miRNAs infrequently expressed in colon-specific carcinoma tissue were associated with CRC survival if highly expressed. Evaluation of miRNAs::mRNA associations showed that mRNA expression influenced by infrequently expressed miRNA contributed to networks and pathways shown to influence disease progression and prognosis. Our large study enabled us to examine the implications of infrequently expressed miRNAs after removal of background noise. These results require replication in other studies. Confirmation of our findings in other studies could lead to important markers for prognosis.