线粒体三功能蛋白亚基A、B在肝门部胆管癌中的临床意义

Clinical significance of HADHA and HADHB expression in hilar cholangiocarcinoma

目的检测线粒体三功能蛋白亚基HADHA及HADHB在肝门部胆管癌中的表达情况,探讨其与肿瘤发展及患者预后的关系。方法构建含91例肝门部胆管癌病例的组织芯片,应用免疫组织化学方法检测HADHA及HADHB在肝门部胆管癌中的表达,并分析其与临床病理参数及预后之间的关系。结果 HADHA及HADHB在肝门部胆管癌中的高表达率分别为71.4%(65/91)、59.3%(54/91),均显著高于癌旁组织的10.4%(5/48)、20.8%(10/48),差异有统计学意义(P<0.05)。HADHA表达与肿瘤浸润深度及手术切缘有关(P<0.05),HADHB表达与手术切缘及淋巴结转移有关(P<0.05)。HADHA、HADHB高表达患者的中位生存期和无进展生存期分别短于HADHA、HADHB低表达患者,差异均有统计学意义(P<0.05)。Cox风险比例回归模型显示,肿瘤浸润深度、淋巴结转移情况、分化程度及HADHB表达均是影响患者预后的独立因素(P<0.05)。结论 HADHA及HADHB在肝门部胆管癌的发生发展过程中发挥了癌基因的作用,可能与肿瘤细胞的侵袭性生物学行为有关,并且HADHB可作为判断患者预后的独立指标。

Objective To investigate the expression pattern of mitochondrial trifunctional protein subunit HADHA and HADHB in the progression of hilar cholangiocarcinoma and to evaluate its clinical significance in the outcome of cancer patients. Methods The tissue microarray was constructed which contains 91 cases of hilar cholangiocarcinoma. Immunohistochemistry was applied to screen the expression of HADHA and HADHB. The expression levels were statistically analyzed to investigate their correlation with clinicopathological features and survival duration of patients. Results The over-expression rates of HADHA and HADHB proteins were71. 4%（ 65/91） and 59. 3%（ 54/91）,higher than 10. 4%（ 5/48）,20. 8%（ 10/48） of adjacent normal tissues with statistical significance（ P〈0. 05）. The expression of HADHA was significantly related with tumor invasion depth and surgical margin（ P〈0. 05）,and HADHB expression was significantly associated with surgical margin and nodal metastasis（ P〈0. 05）. The over-expression of HADHA and HADHB could both shorten the overall survival（ OS） and progression-free survival（ PFS） of patients. Patients with high HADHA and HADHB expression had a lower PFS and OS than those with low HADHA and HADHB expression,respectively（ P〈0. 05）. Cox proportional hazard model showed that tumor invasion depth,nodal metastasis,differentiated degree and HADHB were independent prognostic factor for patients with hilar cholangiocarcinoma. Conclusion HADHA and HADHB play remarkably oncogenic roles in the progression of hilar cholangiocarcinoma. HADHB alone is also an independent prognostic factor for cancer patients. HADHA and HADHB can be promising therapeutic targets for the treatment of hilar cholangiocarcinoma in the future.