National Hepatobiliary and Enteric Surgery Research Center of Ministry of Health, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha, Hunan, China.
Pathol Oncol Res. 2012 Oct;18(4):1039-45. doi: 10.1007/s12253-012-9542-8. Epub 2012 Jul 10.
Lung adenocarcinoma is the most frequently histologic subtype and the most histologically heterogeneous form of lung cancer. De-regulation of Wnt/β-catenin signaling pathway is implicated in lung carcinogenesis. SOX7, as a member of high mobility group (HMG) transcription factor family, plays a role in the modulation of the Wnt/β-catenin signaling pathway. However, the expression pattern and clinicopathological significance of SOX7 in patients with lung adenocarcinoma is still unclear. To address this problem, the SOX7 mRNA expression was detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Immunohistochemical studies were performed on 288 pairs of adjacent normal lung and lung adenocarcinoma tissues with complete follow-up records. Association of SOX7 protein expression with clinical outcomes was evaluated using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model. SOX7 mRNA expression was significantly down-regulated in lung adenocarcinoma compared with matched adjacent normal tissues (P < 0.001). SOX7 protein was expressed in the cytoplasm of lung adenocarcinoma cells in 106/288 (36.8 %) of cases, whereas its immunoreactivities were predominantly located in the cytoplasm of the adjacent normal tissues. The reduced SOX7 expression was correlated with poor differentiation (P = 0.002), lymph node metastasis (P = 0.011) and advanced TNM stage (P = 0.006). Regarding patient survival, the overall survival and the disease-free survival rates were both significantly lower in patients with SOX7-negative tumors than in those with SOX7-positive tumors (P = 0.018 and 0.013, respectively). Multivariate analysis using a Cox proportional-hazards model demonstrated that SOX7 expression status was an independent prognostic factor predicting the overall survival and the disease-free survival of patients with lung adenocarcinoma (P = 0.021 and 0.016, respectively).Our data suggest that the decreased expression of SOX7 is an important feature of lung adenocarcinoma. The expression level of SOX protein may be a useful prognostic marker for patients with lung adenocarcinoma.
肺腺癌是最常见的组织学亚型，也是肺癌中最具组织学异质性的形式。Wnt/β-连环蛋白信号通路的失调与肺癌的发生有关。SOX7 作为高迁移率族（HMG）转录因子家族的一员，在调节 Wnt/β-连环蛋白信号通路中发挥作用。然而，SOX7 在肺腺癌患者中的表达模式和临床病理意义尚不清楚。为了解决这个问题，通过实时定量逆转录聚合酶链反应（qRT-PCR）检测 SOX7mRNA 的表达。对 288 对具有完整随访记录的相邻正常肺组织和肺腺癌组织进行免疫组织化学研究。使用 Kaplan-Meier 方法和多变量 Cox 比例风险回归模型评估 SOX7 蛋白表达与临床结局的关系。与匹配的相邻正常组织相比，肺腺癌中 SOX7mRNA 的表达明显下调（P<0.001）。在 288 例病例中的 106 例（36.8%）肺腺癌细胞的细胞质中表达 SOX7 蛋白，而其免疫反应活性主要位于相邻正常组织的细胞质中。SOX7 表达降低与分化不良（P=0.002）、淋巴结转移（P=0.011）和晚期 TNM 分期（P=0.006）相关。就患者生存而言，SOX7 阴性肿瘤患者的总生存率和无病生存率均明显低于 SOX7 阳性肿瘤患者（P=0.018 和 0.013）。使用 Cox 比例风险模型的多变量分析表明，SOX7 表达状态是预测肺腺癌患者总生存率和无病生存率的独立预后因素（P=0.021 和 0.016）。我们的数据表明，SOX7 表达的降低是肺腺癌的一个重要特征。SOX 蛋白的表达水平可能是肺腺癌患者有用的预后标志物。
