单羧酸转运蛋白MCT1和MCT4在肾透明细胞癌中的表达水平作为靶向治疗预后指标的研究

The Study of the Expression of MCT1 and MCT4 as a Prognostic Indicator of Targeted Therapy in Renal Clear Cell Carcinoma

摘要: 目的：靶向治疗晚期肾透明细胞癌远未达到临床预想的效果。如何能寻找一种能够预测其治疗效果的生物标志物成为迫切需要解决的问题。本课题主要研究单羧酸转运蛋白MCT1和MCT4的表达水平与晚期肾癌靶向治疗疗效之间的关系，以期望找到准确的靶向治疗肾癌的预后因子。方法：采用组织芯片法检测2009~2017年75例接受索拉非尼或舒尼替尼治疗的肾透明细胞癌(clear cell renal cell carcinoma, ccRCC)组织中MCT1、MCT4的表达，探讨其与临床及病理指标以及预后之间的关系。结果：MCT1、MCT4的表达与年龄、肿瘤直径、肿瘤分期、Furmann分级、MSKCC无显著性差异(P > 0.05)。生存分析结果显示MCT1高表达与总生存期OS (P = 0.023, HR = 0.14, 95%CI = 0.03~0.50)以及肿瘤无进展期PFS (P = 0.026, HR = 0.19, HR = 0.19, 95%CI = 0.07~0.54)显著相关。MCT4高表达与OS (P = 0.015, HR = 0.16, 95%CI = 0.04~0.56)和PFS (P = 0.03, HR = 0.29 95%CI = 0.12~0.73)显著有关。COX回归分析显示MCT4为独立预后因素，MCT4高表达与OS (P = 0.03, HR = 0.09, 95%CI = 0.12~0.82)和PFS (P = 0.047, HR = 0.35, 95%CI = 0.12~0.99)显著有关。MCT1表达水平与PFS相关(P = 0.014, HR = 0.26, 95%CI = 0.09~0.76)而与OS无显著相关(P = 0.79)。结论：MCT1和MCT4的表达水平与OS和PFS明显相关。肿瘤MCT1、MCT4表达水平是预测ccRCC或靶向治疗疗效预后的独立因素，因此MCT1和MCT4表达水平可能成为预测靶向治疗效果的新生物标记物。

Abstract: Purpose: Targeted therapy for advanced renal clear cell carcinoma is far from achieving the expected clinical effect. How to find a biomarker that can predict its therapeutic effect has become an urgent problem to be solved. This project is to study the relationship between the expression levels of MCT1 and MCT4 and the efficacy of targeted therapy in advanced renal cell carcinoma, in order to find the accurate prognostic factors of targeted therapy for renal cell carcinoma. Methods: Tissue microarray was used to detect the expression of MCT1 and MCT4 in 75 cases of clear cell renal cell carcinoma (ccRCC) treated with sorafenib or sunitinib from 2009 to 2017. Results: The expression of MCT1 and MCT4 had no significant difference with age, tumor diameter, tumor stage, Furmann grade and MSKCC (P > 0.05). Survival analysis showed that high expression of MCT1 was significantly associated with OS (P = 0.023, HR = 0.14, 95%CI = 0.03~0.50) and PFS (P = 0.026, HR = 0.19, HR = 0.19, 95%CI = 0.07~0.54). High expression of MCT4 was significantly associated with OS (P = 0.015, HR = 0.16, 95%CI = 0.04~0.56) and PFS (P = 0.03, HR = 0.29, 95%CI = 0.12~0.73). Cox regression analysis showed that MCT4 was an independent prognostic factor. High expression of MCT4 was significantly associated with OS (P = 0.03, HR = 0.09, 95%CI = 0.12~0.82) and PFS (P = 0.047, HR = 0.35, 95%CI = 0.12~0.99). MCT1 expression was correlated with PFS (P = 0.014, HR = 0.26, 95%CI = 0.09~0.76), but not with OS (P = 0.79). Conclusion: The expression levels of MCT1 and MCT4 were significantly correlated with OS and PFS. The expression levels of MCT1 and MCT4 are independent factors for predicting the prognosis of ccRCC or targeted therapy. Therefore, the expression levels of MCT1 and MCT4 may become new biomarkers for predicting the effect of targeted therapy.