Department of Surgical Oncology, The Fourth Hospital of Harbin Medical University, Harbin 150001, China.
Med Oncol. 2012 Dec;29(4):2710-5. doi: 10.1007/s12032-012-0171-6.
Hypoxia-induced factors (HIFs) play a central role in the adaptive mechanisms of cancer cells to survive under conditions of hypoxia. HIFs are regulated by prolyl hydroxylases (PHDs) among which PHD3 is implicated as a tumor suppressor. We aimed to correlate PHD3 expression with clinicopathologic parameters and to evaluate its prognostic significance in gastric cancer. The 101 tissue samples were collected from 83 resected stages I–IV gastric cancer patients, which were grouped as non-cancerous mucosa (n=18) and primary carcinoma (n=83). PHD3 expression was evaluated by immunohistochemistry. We adopted Pearson chi-square test, univariate analysis, multivariate analysis and Kaplan–Meier method. The positive frequency of PHD3 in cancer cells was 42.2%, whereas non-cancerous mucosa had no detectable PHD3. The expression of PHD3 increased significantly from non-cancerous mucosa to cancer. A significant difference was observed between PHD3 expression and tumor differentiation (P=0.007). The overexpression of PHD3 was associated with well differentiation. In univariate analyses, American Joint Committee on Cancer (AJCC) stage (P<0.0001), pT classification (P<0.0001), pN classification (P<0.0001), differentiation (P=0.0121), peritoneal metastasis (P=0.0006) and gross features (P=0.0104) were significantly associated with survival except PHD3 (P=0.2228) (Table 3). In multivariate analysis, AJCC stage was prognostically independent [hazard ratio (HR), 3.078; 95% confidence interval (CI), 2.228–4.252; P<0.0001]. Overexpression of PHD3 is a favorable prognosticator for gastric cancer. AJCC stage is an independent prognostic factor of gastric cancer.
缺氧诱导因子（HIFs）在肿瘤细胞适应缺氧环境的机制中发挥核心作用。HIFs 受脯氨酰羟化酶（PHD）调节，其中 PHD3 被认为是一种肿瘤抑制因子。我们旨在将 PHD3 表达与临床病理参数相关联，并评估其在胃癌中的预后意义。从 83 例接受手术治疗的 I-IV 期胃癌患者中收集了 101 个组织样本，分为非癌性黏膜（n=18）和原发性癌（n=83）。通过免疫组织化学评估 PHD3 表达。我们采用 Pearson χ2 检验、单因素分析、多因素分析和 Kaplan-Meier 方法。癌细胞中 PHD3 的阳性频率为 42.2%，而非癌性黏膜中则无法检测到 PHD3。PHD3 的表达从非癌性黏膜到癌症显著增加。PHD3 表达与肿瘤分化之间存在显著差异（P=0.007）。PHD3 的过表达与良好分化相关。在单因素分析中，美国癌症联合委员会（AJCC）分期（P<0.0001）、pT 分类（P<0.0001）、pN 分类（P<0.0001）、分化（P=0.0121）、腹膜转移（P=0.0006）和大体特征（P=0.0104）与生存显著相关，除 PHD3 外（P=0.2228）（表 3）。在多因素分析中，AJCC 分期是独立的预后因素[风险比（HR），3.078；95%置信区间（CI），2.228–4.252；P<0.0001]。PHD3 的过表达是胃癌的有利预后因素。AJCC 分期是胃癌的独立预后因素。
