Department of Pathology, Eulji University School of Medicine, Daejeon 301‑070, Republic of Korea.
Oncol Rep. 2012 Nov;28(5):1701-8. doi: 10.3892/or.2012.2012. Epub 2012 Sep 3.
Based on a previous finding that endothelial cell-specific molecule-1 (ESM-1) is a potential serum marker for colorectal cancer (CRC), the aim of this study was to clarify the clinicopathological significance of ESM-1 expression in CRC, and to explore the correlation between ESM-1 and HIF-1α in the tumorigenesis of CRC related to hypoxic conditions. ESM-1 mRNA expression was examined in CRC and corresponding normal mucosal tissues by reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. This experiment confirmed that ESM-1 levels were high in CRC. We screened the tissue samples of 143 CRC patients. By immunohistochemistry, we determined that the ESM-1 immunoreactivity was significantly correlated with the tumor size, depth of invasion, nodal status, distant metastasis and Dukes' stage, and was an independent prognostic factor for disease recurrence and worse survival outcome (P=0.001). The modulation of ESM-1 under hypoxia was investigated, and it was confirmed that ESM-1 expression was induced by HIF1-α and significantly attenuated by small interfering RNA (siRNA) targeting HIF-1α in CRC cells. These results showed that ESM-1 is significantly overexpressed, which is regulated by HIF-1α in CRC patients, and can be used as a potential biomarker and a therapeutic target for CRC.
基于先前的研究发现，内皮细胞特异性分子-1（ESM-1）是结直肠癌（CRC）的一种潜在血清标志物，本研究旨在阐明 ESM-1 在 CRC 中的临床病理意义，并探讨 ESM-1 与缺氧条件下 CRC 肿瘤发生相关的 HIF-1α 之间的相关性。通过逆转录-聚合酶链反应（RT-PCR）和实时 RT-PCR 检测 CRC 和相应正常黏膜组织中的 ESM-1 mRNA 表达。该实验证实 ESM-1 在 CRC 中表达水平较高。我们筛选了 143 例 CRC 患者的组织样本。通过免疫组织化学，我们确定 ESM-1 免疫反应性与肿瘤大小、浸润深度、淋巴结状态、远处转移和 Dukes 分期显著相关，并且是疾病复发和生存结局恶化的独立预后因素（P=0.001）。研究了缺氧下 ESM-1 的调节，证实 HIF1-α 诱导 ESM-1 表达，并通过针对 HIF-1α 的小干扰 RNA（siRNA）显著减弱 CRC 细胞中的 ESM-1 表达。这些结果表明，ESM-1 在 CRC 患者中显著过表达，受 HIF-1α 调控，可作为 CRC 的潜在生物标志物和治疗靶点。
