Shi Mo, Wang Zhou, Liu Xiang-Yan, Chen Dong
Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China.
Med Oncol. 2014 Dec;31(12):309. doi: 10.1007/s12032-014-0309-9. Epub 2014 Nov 13.
The inactivation of RUNX3 in various cancers has been reported while the expression of RUNX3 on protein level in esophageal squamous cell carcinoma (ESCC) and its relationship with pathological parameters and prognosis still remained unclear. In this study, we examined the expression of RUNX3 in 158 ESCC samples and 20 normal esophageal mucosa samples by immunohistochemistry and qRT-PCR. The IHC result showed that RUNX3 was detected mainly in the nuclei of basal layer cells in 18 of 20 normal mucosa samples while in 158 ESCC samples, there were 46 with RUNX3 nuclei expression, 37 RUNX3 cytoplasmic expression, and 75 negative expression. The qRT-PCR confirmed the downregulation of RUNX3 mRNA in the RUNX3 protein negative group than in the RUNX3 nuclei and cytoplasmic expression group (P < 0.001), and the methylation-specific PCR showed a low methylation rate in the ESCC tissue samples with RUNX3 protein negative expression (6/40, 15%). The RUNX3 nuclei expression negatively correlated with the lymph node metastasis (P = 0.033) and recurrence status (P = 0.019), and the survival analysis showed that the patients with RUNX3 nuclei expression had a higher 5-year survival rate than the patients with RUNX3 cytoplasmic/negative expression (P = 0.022). The Cox regression analysis showed that the T classification (P = 0.001), lymph node metastasis (P < 0.001), and RUNX3 inactivation (negative/cytoplasmic expression, P = 0.039) were independent risk factor of poor prognosis. In conclusion, we found a frequent inactivation of RUNX3 due to low expression and cytoplasmic dislocalization in ESCC. The inactivation of RUNX3 may be involved in the progression of ESCC, and RUNX3 could be an indicator of prognosis for patients with ESCC after surgery.
已有报道称RUNX3在多种癌症中失活，然而食管鳞状细胞癌（ESCC）中RUNX3蛋白水平的表达及其与病理参数和预后的关系仍不清楚。在本研究中，我们通过免疫组织化学和qRT-PCR检测了158例ESCC样本和20例正常食管黏膜样本中RUNX3的表达。免疫组织化学结果显示，20例正常黏膜样本中有18例RUNX3主要在基底层细胞核中检测到，而在158例ESCC样本中，有46例RUNX3呈细胞核表达，37例呈细胞质表达，75例呈阴性表达。qRT-PCR证实RUNX3蛋白阴性组中RUNX3 mRNA的下调程度高于RUNX3细胞核和细胞质表达组（P < 0.001），甲基化特异性PCR显示RUNX3蛋白阴性表达的ESCC组织样本中甲基化率较低（6/40，15%）。RUNX3细胞核表达与淋巴结转移（P = 0.033）和复发状态（P = 0.019）呈负相关，生存分析显示RUNX3细胞核表达的患者5年生存率高于RUNX3细胞质/阴性表达的患者（P = 0.022）。Cox回归分析显示T分期（P = 0.001）、淋巴结转移（P < 0.001）和RUNX3失活（阴性/细胞质表达，P = 0.039）是预后不良的独立危险因素。总之，我们发现ESCC中由于低表达和细胞质异位导致RUNX3频繁失活。RUNX3失活可能参与ESCC的进展，RUNX3可能是ESCC患者术后预后的一个指标。
