线粒体丙酮酸载体在肝细胞癌中的表达及临床意义

摘要/Abstract

摘要： 目的探讨线粒体丙酮酸载体(mitochondrial pyruvate carriers, MPC)在肝细胞癌组织中的表达水平及其对复发和预后的指导价值。方法通过免疫组织化学法检测85例手术切除的肝细胞癌石蜡标本中癌和癌旁组织的MPC1和MPC2的表达水平, 分析其与临床病理学指标的相关性。Kaplain-Meier分析MPC表达水平与肝细胞癌患者复发及预后的相关性。建立COX回归分析模型, 对MPC1和MPC2蛋白表达水平和临床病理学指标进行单因素和多因素分析, 寻找肝细胞癌术后复发的独立危险因素。结果与癌旁组织相比, 癌组织中MPC1和MPC2蛋白表达水平均明显降低。MPC1和MPC2的蛋白表达水平和临床病理学指标均无明显相关性(P>0.05)。MPC1蛋白表达水平低的肝细胞癌患者的术后复发率升高(P=0.000)且总体生存时间缩短(P=0.001);MPC2的蛋白表达水平与复发(P=0.254)和总生存期无相关性(P=0.452)。MPC1蛋白表达水平降低(P=0.000)和微血管侵润(P=0.017)是肝细胞癌患者术后复发的独立危险因素;单因素和多因素分析显示MPC2(P=0.230)和患者术后复发无关。结论在肝细胞癌中MPC1和MPC2的蛋白活性下降或缺失是普遍存在的, 且MPC1的蛋白表达水平与患者的术后复发和预后存在明显的相关性, 可成为新的判断肝细胞癌患者临床预后、对术后患者进行风险分层的生物标记物。

关键词: 肝细胞癌, 线粒体丙酮酸载体, 生存分析, 预后, 能量代谢

Abstract: Objective Mitochondrial pyruvate carrier (MPC) plays an important pathophysiological role in the metabolism of tumor cells. However, there are few studies about the effects of MPC in the development of malignant tumors, especially hepatocellular carcinoma (HCC). The aim of this study was to analyze the correlation between the expression of MPC in HCC and the levels of clinicopathological parameters, and to evaluate the predictive value of MPC for recurrence and prognosis of HCC after operation.Methods MPC1 and MPC2 protein expression levels in 85 cases of carcinoma and adjacent tissue specimens were detected by immunohistochemistry. The relative expression levels of MPC1 and MPC2 were calculated by Image-Pro Plus software. The correlation between the protein expressions of MPC1 and MPC2 and the levels of clinical pathological parameters was analyzed between patients grouped according to the relative expressions of MPC1 and MPC2. Kaplain-Meier survival analysis was used to analyze the correlation between the protein expression of MPC and the recurrence, prognosis of patients with HCC. Cox regression models were established to determine independent risk factors for recurrence of HCC after operation.Results In paraffin-embedded specimens, the protein expressions of MPC1 and MPC2 in tumor tissues were significantly lower than those in adjacent tissues. There was no significant correlation between MPC1, MPC2 levels and clinical pathological parameters (P>0.05). In patients with lower expression of MPC1, the recurrence rate (P=0.000) was higher and the overall survival time (P=0.001) was shorter. However, the expression level of MPC2 was not correlated with recurrence rate (P=0.254) or overall survival (P=0.452). The decreased expression of MPC1 protein (P=0.000) and microvascular invasion (P=0.017) were independent risk factors for postoperative recurrence of HCC. Univariate and multivariate analyses showed that MPC2 was not associated with postoperative recurrence (P=0.230).Conclusion The absence or reduced activity of MPC1 and MPC2 protein in HCC is widespread. And the expression of MPC1 protein is associated with postoperative recurrence and prognosis of HCC, which can be used as a new biomarkers for clinical prognosis prediction and risk stratification in postoperative patients with HCC.

Key words: Hepatocellular carcinoma, Mitochondrial pyruvate carrier, Survival analysis, Prognosis, Energy metabolism

马向明, 侯婧悦, 付庆江, 曹立瀛. 线粒体丙酮酸载体在肝细胞癌中的表达及临床意义[J]. 肝脏, 2020, 25(6): 573-577.

MA Xiang-ming, HOU Jing-yue, FU Qing-jiang, CAO Li-ying.. The clinical and pathological significance of mitochondrial pyruvate carriers in hepatocellular carcinoma[J]. Chinese Hepatolgy, 2020, 25(6): 573-577.

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