Expression of pyruvate dehydrogenase is an independent prognostic marker in gastric cancer.
Expression of pyruvate dehydrogenase is an independent prognostic marker in gastric cancer.
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DOI：
10.3748/wjg.v21.i17.5336
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发表时间：
2015-05
影响因子：
4.3
通讯作者：
Xuren Sun;Zhe Sun;Zhi Zhu;H. Guan;Chen-yan Li;Jun-Yan Zhang;Yi-ning Zhang;Huan Zhou;Hui-jing Zhang;Hui-mian Xu;Ming-jun Sun
中科院分区：
文献类型：
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作者：
Xuren Sun;Zhe Sun;Zhi Zhu;H. Guan;Chen-yan Li;Jun-Yan Zhang;Yi-ning Zhang;Huan Zhou;Hui-jing Zhang;Hui-mian Xu;Ming-jun Sun
目的探讨丙酮酸脱氢酶（PDH）在胃癌组织中的表达及其与预后的关系。方法2006 - 01/2007 - 05在中国医科大学附属第一医院行根治性手术治疗的胃癌患者265例，男194例，女71例，年龄29-81岁，平均59岁。所有患者均随访5年以上。收集患者来源的石蜡包埋的GC标本用于组织微阵列（TMA）。我们通过免疫组化检测了含有肿瘤组织和匹配的非肿瘤粘膜的TMAs中PDH的表达。免疫反应性由两名研究人员独立评价。使用Kaplan-Meier估计值确定总生存率（OS）。通过双尾χ（2）检验或双尾t检验评估与其他临床病理因素的相关性。采用考克斯比例风险模型进行单因素分析和多因素分析，以确定与预后显著相关的因素。结果免疫组化显示35.47%的癌组织胞浆PDH阳性。PDH在正常胃黏膜中的表达率为75.09%（P = 0.001）。PDH表达与Lauren分级相关（肠型70.77% vs弥漫型40.0%; P = 0.001），淋巴结转移（65.43%无转移vs 51.09%有转移; P = 0.033），淋巴管浸润（61.62%无浸润vs 38.81%有浸润; P = 0.002），组织学亚型肠型占70.77%，弥漫型占40.0%;胃癌的TNM分期（低分化组39%，高分化组65.91%，中分化组67.11%，P = 0.001）。癌组织中PDH的表达与较高的OS显著相关（P < 0.001）。经年龄、Lauren分期、TNM分期、淋巴结转移、组织学类型、肿瘤大小、浸润深度、淋巴结转移等因素校正后的多因素分析显示，PDH表达是影响胃癌患者生存率的独立预后因素（HR = 0.608，95%CI：0.504-0.734，P < 0.001）。结论PDH表达是胃癌患者的独立预后因素，PDH阳性表达可能预示良好的预后。
AIM To investigate the expression and prognostic role of pyruvate dehydrogenase (PDH) in gastric cancer (GC). METHODS This study included 265 patients (194 male, 71 female, mean age 59 years (range, 29-81 years) with GC who underwent curative surgery at the First Affiliated Hospital of China Medical University from January 2006 to May 2007. All patients were followed up for more than 5 years. Patient-derived paraffin embedded GC specimens were collected for tissue microarrays (TMAs). We examined PDH expression by immunohistochemistry in TMAs containing tumor tissue and matched non-neoplastic mucosa. Immunoreactivity was evaluated independently by two researchers. Overall survival (OS) rates were determined using the Kaplan-Meier estimator. Correlations with other clinicopathologic factors were evaluated by two-tailed χ(2) tests or a two-tailed t-test. The Cox proportional-hazard model was used in univariate analysis and multivariate analysis to identify factors significantly correlated with prognosis. RESULTS Immunohistochemistry showed that 35.47% of total cancer tissue specimens had cytoplasmic PDH staining. PDH expression was much higher in normal mucosa specimens (75.09%; P = 0.001). PDH expression was correlated with Lauren grade (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001), lymph node metastasis (65.43% with no metastasis vs 51.09% with metastasis; P = 0.033), lymphatic invasion (61.62% with no invasion vs 38.81% with invasion; P = 0.002), histologic subtypes (70.77% in intestinal type vs 40.0% in diffuse type; P = 0.001) and tumor-node-metastasis (TNM) stage (39% in poorly differentiated vs 65.91% in well differentiated and 67.11% in moderately differentiated; P = 0.001) in GC. PDH expression in cancer tissue was significantly associated with higher OS (P < 0.001). The multivariate analysis adjusted for age, Lauren classification, TNM stage, lymph node metastasis, histological type, tumor size, depth of invasion and lymphatic invasion showed that the PDH expression in GC was an independent prognostic factor for higher OS (HR = 0.608, 95%CI: 0.504-0.734, P < 0.001). CONCLUSION Our study indicated that PDH expression is an independent prognostic factor in GC patients and that positive expression of PDH may be predictive of favorable outcomes.