Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.
Cancer Epidemiol. 2012 Feb;36(1):e61-7. doi: 10.1016/j.canep.2011.05.002. Epub 2011 Oct 21.
Colorectal cancer (CRC) metastasis occurs in various organs, most frequently in liver. Serological examination including tumor and biochemical markers for liver function evaluation is routinely performed, though its accuracy is not high. MicroRNAs (miRNAs) have been implicated in a variety of human diseases including cancer, and have many characteristics of an ideal biomarker most notably their inherent stability and resilience. Recently, several studies have indicated that circulating miRNAs hold much potential as novel noninvasive biomarkers for cancer and other disease processes. The objective of this study was to investigate the potential of serum miRNAs as novel biomarkers for CRC with liver metastasis.
This study was divided into three phases: (I) 3 candidate serum miRNAs were detected by using real-time RT-PCR, corresponding 38 CRC patients with liver metastasis and 36 CRC patients without metastasis. (II) Marker validation by real-time RT-PCR on a similar cohort of age- and sex-matched CRC patients without (n=20) and with liver metastasis (n=20). (III) We examined the correlation between the expressions of candidate serum miRNAs with clinical parameters of CRC patients.
Serum miR-29a was significantly higher in colorectal liver metastasis (CRLM) patients than in CRC patients. This marker yielded a receiver operating characteristic curve area of 80.3%. At a cutoff value of 0.155, the sensitivity was 75% and the specificity was 75% in discriminating metastatic from non-metastatic patients. In addition, increased levels of miR-29a expression were also observed in colorectal tumors from CRLM patients compared with CRC patients. No significant difference was observed in the levels of serum miR-92a between metastatic and non-metastatic patients.
These findings suggest that serum miR-29a has strong potential as a novel noninvasive biomarker for early detection of CRC with liver metastasis.
结直肠癌(CRC)转移发生在各种器官中,最常见于肝脏。通常进行包括肿瘤和肝功能生化标志物在内的血清学检查,但准确性不高。微小 RNA(miRNA)与包括癌症在内的多种人类疾病有关,并且具有作为理想生物标志物的许多特征,最显著的是它们固有的稳定性和弹性。最近,几项研究表明,循环 miRNA 作为癌症和其他疾病过程的新型非侵入性生物标志物具有很大的潜力。本研究旨在探讨血清 miRNA 作为结直肠癌伴肝转移新型生物标志物的潜力。
本研究分为三个阶段:(I)使用实时 RT-PCR 检测 3 种候选血清 miRNA,对应 38 例伴有肝转移的 CRC 患者和 36 例无转移的 CRC 患者。(II)对年龄和性别匹配的无(n=20)和有肝转移(n=20)CRC 患者的类似队列进行实时 RT-PCR 验证。(III)我们检查候选血清 miRNA 的表达与 CRC 患者临床参数之间的相关性。
结直肠癌肝转移(CRLM)患者血清 miR-29a 水平明显高于 CRC 患者。该标志物的受试者工作特征曲线面积为 80.3%。在 0.155 的截止值处,区分转移和非转移患者的敏感性为 75%,特异性为 75%。此外,在 CRLM 患者的结直肠肿瘤中也观察到 miR-29a 表达水平升高。转移和非转移患者之间血清 miR-92a 水平无显著差异。
这些发现表明,血清 miR-29a 作为一种新型非侵入性生物标志物,具有早期检测结直肠癌伴肝转移的潜力。