Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Ann Surg Oncol. 2011 Dec;18(13):3858-67. doi: 10.1245/s10434-011-1668-5. Epub 2011 Mar 26.
Our previous study observed that the expression of RASSF6, a member of the Ras-association domain family, was down-regulated in gastric cancer cells. The present study further investigated the clinical significance of RASSF6 in gastric cancer.
Using real-time PCR, Western blot analysis, tissue microarray (TMA), and immunohistochemical staining, we evaluated RASSF6 mRNA and protein levels in tumor tissues and in the paired adjacent normal mucosa from patients with gastric cancers at different stages.
RASSF6 mRNA and protein levels were decreased in gastric cancer tissues compared with the adjacent normal mucosa. Immunohistochemical detection of RASSF6 in a TMA that contained 264 paired specimens showed that a decreased cytoplasmic RASSF6 expression was significantly associated with the extent of cancer invasion, lymph node metastasis, distant metastasis, tumor histological grade, advanced clinical stage, and Ki-67 proliferative index. Moreover, RASSF6 expression in metastatic lymph nodes was lower than in the paired primary tumors. Patients with RASSF6-negative tumors had extremely higher disease recurrence rates and poorer survival than patients with RASSF6-positive tumors even after radical surgery. Stratification analysis revealed RASSF6 as an independent predictor for tumor recurrence in patients with gastric cancers irrespective of tumor stage.
RASSF6 might contribute to the progression of gastric carcinogenesis and may function as a novel independent prognostic marker for the prediction of the recurrence of cancer in patients after curative operations.
我们之前的研究观察到 Ras 相关结构域家族成员 RASSF6 在胃癌细胞中的表达下调。本研究进一步探讨了 RASSF6 在胃癌中的临床意义。
采用实时 PCR、Western blot 分析、组织微阵列（TMA）和免疫组织化学染色，我们评估了不同阶段胃癌患者肿瘤组织和配对的相邻正常黏膜中 RASSF6 mRNA 和蛋白水平。
与相邻正常黏膜相比，胃癌组织中 RASSF6 mRNA 和蛋白水平降低。在包含 264 对标本的 TMA 中对 RASSF6 进行免疫组化检测表明，细胞质 RASSF6 表达降低与癌症浸润程度、淋巴结转移、远处转移、肿瘤组织学分级、晚期临床分期和 Ki-67 增殖指数显著相关。此外，转移性淋巴结中的 RASSF6 表达低于配对的原发性肿瘤。即使在根治性手术后，RASSF6 阴性肿瘤患者的疾病复发率和生存预后明显比 RASSF6 阳性肿瘤患者更差。分层分析显示，RASSF6 是胃癌患者肿瘤复发的独立预测因子，与肿瘤分期无关。
RASSF6 可能有助于胃癌的发生发展，并且可以作为预测根治性手术后癌症复发的新的独立预后标志物。
