Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute, Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, USA.
Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie Japan.
Ann Oncol. 2017 Aug 1;28(8):1882-1888. doi: 10.1093/annonc/mdx248.
8q24.21 is a frequently amplified genomic region in colorectal cancer (CRC). This region is often referred to as a 'gene desert' due to lack of any important protein-coding genes, highlighting the potential role of noncoding RNAs, including long noncoding RNAs (lncRNAs) located around the proto-oncogene MYC. In this study, we have firstly evaluated the clinical significance of altered expression of lncRNAs mapped to this genomic locus in CRC.
A total of 300 tissues, including 280 CRC and 20 adjacent normal mucosa specimens were evaluated for the expression of 12 lncRNAs using qRT-PCR assays. We analyzed the associations between lncRNA expression and various clinicopathological features, as well as with recurrence free survival (RFS) and overall survival (OS) in two independent cohorts.
The expression of CCAT1, CCAT1-L, CCAT2, PVT1, and CASC19 were elevated in cancer tissues (P = 0.039, <0.001, 0.018, <0.001, 0.002, respectively). Among these, high expression of CCAT1 and CCAT2 was significantly associated with poor RFS (P = 0.049 and 0.022, respectively) and OS (P = 0.028 and 0.015, respectively). These results were validated in an independent patient cohort, in which combined expression of CCAT1 and CCAT2 expression was significantly associated with a poor RFS (HR:2.60, 95% confidence interval [CI]: 1.04-6.06, P = 0.042) and a poor OS (HR:8.38, 95%CI: 2.68-37.0, P < 0.001). We established a RFS prediction model which revealed that combined expression of CCAT1, CCAT2, and carcinoembryonic antigen was a significant determinant for efficiently predicting RFS in stage II (P = 0.034) and stage III (P = 0.001) CRC patients.
Several lncRNAs located in 8q24.21 locus are highly over-expressed in CRC. High expression of CCAT1 and CCAT2 significantly associates with poor RFS and OS. The expression of these two lncRNAs independently, or in combination, serves as important prognostic biomarkers in CRC.
8q24.21 是结直肠癌（CRC）中经常扩增的基因组区域。由于缺乏任何重要的蛋白质编码基因，该区域通常被称为“基因荒漠”，这突显了非编码 RNA 的潜在作用，包括位于原癌基因 MYC 周围的长非编码 RNA（lncRNA）。在这项研究中，我们首次评估了映射到该基因组位置的 lncRNA 表达改变在 CRC 中的临床意义。
使用 qRT-PCR 检测了总共 300 个组织，包括 280 个 CRC 和 20 个相邻正常粘膜标本中 12 个 lncRNA 的表达。我们分析了 lncRNA 表达与各种临床病理特征之间的关联，以及在两个独立队列中的无复发生存率（RFS）和总生存率（OS）。
CCAT1、CCAT1-L、CCAT2、PVT1 和 CASC19 在癌组织中的表达升高（P=0.039、<0.001、0.018、<0.001、0.002，分别）。其中，CCAT1 和 CCAT2 的高表达与较差的 RFS（P=0.049 和 0.022，分别）和 OS（P=0.028 和 0.015，分别）显著相关。这些结果在一个独立的患者队列中得到了验证，其中 CCAT1 和 CCAT2 表达的联合表达与较差的 RFS（HR：2.60，95%置信区间[CI]：1.04-6.06，P=0.042）和较差的 OS（HR：8.38，95%CI：2.68-37.0，P<0.001）显著相关。我们建立了一个 RFS 预测模型，该模型揭示了 CCAT1、CCAT2 和癌胚抗原的联合表达是预测 II 期（P=0.034）和 III 期（P=0.001）CRC 患者 RFS 的重要决定因素。
位于 8q24.21 位的几个 lncRNA 在 CRC 中高度过表达。CCAT1 和 CCAT2 的高表达与较差的 RFS 和 OS 显著相关。这两个 lncRNA 的表达，无论是单独的还是联合的，都可以作为 CRC 的重要预后生物标志物。
