Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Ann Surg Oncol. 2011 Jan;18(1):261-72. doi: 10.1245/s10434-010-1271-1. Epub 2010 Aug 24.
We sought to identify genes associated with the progression and metastasis of esophageal squamous-cell cancer by comparing the expression profiles of normal, primary cancer, and metastatic cancer cells isolated with laser microdissection.
Oligo microarray analysis identified several lymph node-specific, metastasis-related genes. STC2 (stanniocalcin 2), which was overexpressed in esophageal cancer cases, was chosen for further characterization. Quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry were used to explore the clinicopathologic significance of STC2 expression status in 70 cases. Additionally, the functional role of STC2 in esophageal cancer was studied by the attenuation of STC2 in an esophageal cancer cell line.
Laser microdissection and oligo microarray analysis identified 63 candidate genes. Among them, STC2 showed higher expression in cancer tissue than in corresponding normal tissue (P < 0.001). STC2 expression was significantly correlated with lymph node metastasis, lymphatic invasion, and distant metastasis (P = 0.005, 0.007, and 0.038, respectively). Patients whose tumors had high STC2 expression had a worse 5-year survival rate than patients whose tumors had a low STC2 expression level (P = 0.016). STC2 transfected cells had a significantly higher proliferation rate than control cells (P < 0.001). Additionally, STC2 transfected cells were more invasive in vitro (P < 0.001) than control cells. These findings were validated by means of RNA interference assays.
We identified lymph node-specific, metastasis-related genes in esophageal cancer cells. One of these, STC2, may be associated with lymph node metastasis, making it a potential prognostic marker for esophageal cancer patients.
我们通过比较激光微切割分离的正常、原发性癌症和转移性癌细胞的表达谱，试图确定与食管鳞状细胞癌进展和转移相关的基因。
寡核苷酸微阵列分析鉴定了几个淋巴结特异性、转移相关基因。在食管癌病例中过度表达的 STC2（斯钙素 2）被选为进一步研究的对象。定量逆转录-聚合酶链反应和免疫组织化学用于在 70 例病例中探索 STC2 表达状态的临床病理意义。此外，通过衰减食管癌细胞系中的 STC2 来研究 STC2 在食管癌中的功能作用。
激光微切割和寡核苷酸微阵列分析鉴定了 63 个候选基因。其中，STC2 在癌症组织中的表达明显高于相应的正常组织（P <0.001）。STC2 表达与淋巴结转移、淋巴管浸润和远处转移显著相关（P = 0.005、0.007 和 0.038）。肿瘤高 STC2 表达的患者比肿瘤低 STC2 表达水平的患者 5 年生存率差（P = 0.016）。与对照细胞相比，转染 STC2 的细胞具有更高的增殖率（P <0.001）。此外，转染 STC2 的细胞在体外的侵袭性更高（P <0.001）。这些发现通过 RNA 干扰实验得到了验证。
我们鉴定了食管癌细胞中与淋巴结特异性、转移相关的基因。其中一种，STC2，可能与淋巴结转移有关，使其成为食管癌患者潜在的预后标志物。
