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单羧酸转运蛋白MCT1和MCT4是透明细胞肾细胞癌患者以及接受抗血管生成治疗患者生存的独立预后生物标志物。

Monocarboxylate transporters MCT1 and MCT4 are independent prognostic biomarkers for the survival of patients with clear cell renal cell carcinoma and those receiving therapy targeting angiogenesis.

作者信息

Cao Yan-Wei, Liu Yong, Dong Zhen, Guo Lei, Kang En-Hao, Wang Yong-Hua, Zhang Wei, Niu Hai-Tao

机构信息

Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

Department of Ultrasondography, Qingdao Haici Hospital, Qingdao, Shandong, China.

出版信息

Urol Oncol. 2018 Jun;36(6):311.e15-311.e25. doi: 10.1016/j.urolonc.2018.03.014. Epub 2018 Apr 12.

Abstract

BACKGROUND

Prognostic biomarkers for patients with clear cell renal cell carcinoma (ccRCC), particularly those receiving therapy targeting angiogenesis, are not well established. In this study, we examined the correlations of monocarboxylate transporter 1 (MCT1) and MCT4, 2 critical transporters for glycolytic metabolism, with various clinicopathological parameters as well as survival of patients with ccRCC and those treated with vascular endothelial growth factor receptor (VEGFR) inhibitors.

METHODS

A cohort of 150 ccRCC patients were recruited into this study. All patients underwent radical or partial nephrectomy as the first-line treatment, and 38 received targeted therapy (sorafenib or sunitinib) after the surgery. Expression levels of MCT1, MCT4, and CD34 were examined by immunohistochemistry. Correlations between MCT1 or MCT4 expression and different clinicopathological parameters or patient survival were analyzed among all as well as patients receiving targeted therapy.

RESULTS

MCT1 or MCT4 expression did not significantly correlate with sex, age, tumor diameter, microvascular density, tumor staging, pathological Furmann grade, or MSKCC (P>0.05). High expression of either MCT1 or MCT4 significantly correlated with reduced overall survival (OS) and progression-free survival (PFS) among the total cohort of ccRCC patients. For patients receiving targeted therapy, high expression of either MCT1 or MCT4 significantly correlated with reduced PFS, but not OS. Both conditions were independent prognostic biomarkers for reduced PFS among all patients or those receiving targeted therapy.

CONCLUSION

MCT1 and MCT4 are prognostic biomarkers for patients with ccRCC or those receiving targeted therapy. High expression of these 2 proteins predicts reduced PFS in these patients.

摘要

背景

透明细胞肾细胞癌(ccRCC)患者,尤其是接受抗血管生成治疗患者的预后生物标志物尚未完全确立。在本研究中,我们检测了糖酵解代谢的两个关键转运蛋白——单羧酸转运蛋白1(MCT1)和MCT4,与ccRCC患者的各种临床病理参数以及生存率之间的相关性,以及与接受血管内皮生长因子受体(VEGFR)抑制剂治疗患者的相关性。

方法

本研究纳入了150例ccRCC患者。所有患者均接受根治性或部分肾切除术作为一线治疗,其中38例患者术后接受了靶向治疗(索拉非尼或舒尼替尼)。采用免疫组织化学法检测MCT1、MCT4和CD34的表达水平。分析了所有患者以及接受靶向治疗患者中MCT1或MCT4表达与不同临床病理参数或患者生存率之间的相关性。

结果

MCT1或MCT4表达与性别、年龄、肿瘤直径、微血管密度、肿瘤分期、病理Furmann分级或MSKCC均无显著相关性(P>0.05)。在ccRCC患者总体队列中,MCT1或MCT4的高表达均与总生存期(OS)和无进展生存期(PFS)降低显著相关。对于接受靶向治疗的患者,MCT1或MCT4的高表达均与PFS降低显著相关,但与OS无关。在所有患者或接受靶向治疗的患者中,这两种情况均是PFS降低的独立预后生物标志物。

结论

MCT1和MCT4是ccRCC患者或接受靶向治疗患者的预后生物标志物。这两种蛋白的高表达预示着这些患者的PFS降低。

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