Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Chin J Cancer Res. 2014 Feb;26(1):95-103. doi: 10.3978/j.issn.1000-9604.2014.02.07.
MicroRNAs (miRNAs) have potential as diagnostic biomarkers in cancer. Evaluation of the association between miRNA expression patterns and early detection of liver metastasis in colorectal cancer (CRC) has not been reported.
We investigated the expression of metastasis-associated miRs-31, 335, 206, 141, 126, 200b, 200c, 21, Let7a, Let7b and Let7c in localized, liver-metastatic and other organ-metastatic CRC (OM-CRC). Expressions of target miRNAs in serum were evaluated in 116 consecutive localized CRC (L-CRC), 72 synchronous liver-metastatic CRC (SLM-CRC) and 36 other OM-CRC by quantitative real-time PCR.
Seven of 11 tested miRNAs could be detected from serum. Four miRNAs, miR-126, Let-7a, miR-141 and miR-21 were identified as metastasis-associated miRNAs. Compared with L-CRC, significant up-regulated expression was observed for miR-141 and miR-21 in SLM-CRC and OM-CRC, down-regulated expression was observed for miR-126 in SLM-CRC and OM-CRC, and up-regulated expression of Let-7a in OM-CRC. The receiver operating characteristic (ROC) curve showed serum miR-126 had a cut-off [log10 relative quantity (log10 (RQ))=-0.2005] with 77.78% sensitivity and 68.97% specificity with an area under curve (AUC) of 0.7564, miR-141 had a cut-off (log10 (RQ)=-0.2285) with 86.11% sensitivity and 76.11% specificity with an AUC of 0.8279, and miR-21 had a cut-off (log10 (RQ)=-0.1310) with 73.61% sensitivity and 66.38% specificity with an AUC of 0.7479.
We identified liver metastasis-associated miRNAs, suggesting serum miR-126, miR-141 and miR-21 may be novel biomarkers for clinical diagnosis of early stage liver-metastatic CRC.
微小 RNA（miRNAs）具有作为癌症诊断生物标志物的潜力。尚未有研究评估 miRNA 表达模式与结直肠癌（CRC）肝转移早期检测之间的关联。
我们研究了转移相关 miR-31、335、206、141、126、200b、200c、21、Let7a、Let7b 和 Let7c 在局部、肝转移和其他器官转移 CRC（OM-CRC）中的表达。通过定量实时 PCR 检测 116 例连续局部 CRC（L-CRC）、72 例同步肝转移 CRC（SLM-CRC）和 36 例其他 OM-CRC 中靶标 miRNA 在血清中的表达。
11 个测试 miRNA 中有 7 个可以从血清中检测到。4 个 miRNA，miR-126、Let-7a、miR-141 和 miR-21 被鉴定为转移相关 miRNA。与 L-CRC 相比，SLM-CRC 和 OM-CRC 中 miR-141 和 miR-21 的表达显著上调，SLM-CRC 和 OM-CRC 中 miR-126 的表达下调，OM-CRC 中 Let-7a 的表达上调。受试者工作特征（ROC）曲线显示，血清 miR-126 的截断值[log10 相对量（log10（RQ））=-0.2005]，灵敏度为 77.78%，特异性为 68.97%，曲线下面积（AUC）为 0.7564，miR-141 的截断值（log10（RQ））=-0.2285），灵敏度为 86.11%，特异性为 76.11%，AUC 为 0.8279，miR-21 的截断值（log10（RQ））=-0.1310），灵敏度为 73.61%，特异性为 66.38%，AUC 为 0.7479。
我们鉴定了与肝转移相关的 miRNAs，提示血清 miR-126、miR-141 和 miR-21 可能是早期肝转移 CRC 临床诊断的新型生物标志物。
