葡萄糖转运蛋白1（SLC2A1）和血管内皮生长因子A（VEGFA）可预测结直肠癌肝转移切除术后的生存率。
Glucose Transporter 1 (SLC2A1) and Vascular Endothelial Growth Factor A (VEGFA) Predict Survival After Resection of Colorectal Cancer Liver Metastasis.
作者信息
Goos Jeroen A C M, de Cuba Erienne M V, Coupé Veerle M H, Diosdado Begoña, Delis-Van Diemen Pien M, Karga Cemile, Beliën Jeroen A M, Menke-Van der Houven van Oordt C Willemien, Geldof Albert A, Meijer Gerrit A, Hoekstra Otto S, Fijneman Remond J A
机构信息
*Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands †Department of Radiology and Nuclear Medicine, VU University Medical Center, Amsterdam, The Netherlands ‡Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands §Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
出版信息
Ann Surg. 2016 Jan;263(1):138-45. doi: 10.1097/SLA.0000000000001109.
OBJECTIVE
To investigate the individual and combined prognostic value of HIF1α, SLC2A1, and vascular endothelial growth factor A (VEGFA) in a multi-institutional cohort of patients with resected colorectal cancer liver metastasis (CRCLM).
BACKGROUND
In the majority of patients with CRCLM, resection seems not to be curative, despite its curative intent. Overexpression of hypoxia-inducible factor 1α (HIF1α), glucose transporter 1 (SLC2A1; also known as GLUT1), and VEGFA has been associated with tumor progression and poor prognosis of patients with colorectal cancer (CRC).
METHODS
Tissue microarrays were generated using CRCLM and patient-matched primary CRC from patients who underwent CRCLM resection between 1990 and 2010. Prognostic value of HIF1α, SLC2A1, and VEGFA was determined by immunohistochemistry. A 500-fold cross-validated hazard rate ratio (HRRav) for overall survival was calculated.
RESULTS
HIF1α, SLC2A1, and VEGFA expression could be evaluated in 328, 350, and 335 patients, respectively. High SLC2A1 expression was associated with good prognosis (HRRav, 0.67; P (HRR >1) < 0.01) and high VEGFA expression to poor prognosis (HRRav, 1.84; P (HRR < 1) = 0.02), also after multivariate analysis including established clinicopathological prognostic variables (HRRav, 0.67; P (HRR > 1) < 0.01 and HRRav, 1.50; P (HRR < 1) = 0.02, respectively). SLC2A1 showed prognostic value particularly in patients treated with systemic therapy (P < 0.01), whereas the prognostic value of VEGFA expression was mainly observed in patients not treated with systemic therapy (P < 0.01). Prognosis was especially poor in patients with both low SLC2A1 and high VEGFA expression (P < 0.01). HIF1α expression was not associated with survival.
CONCLUSIONS
SLC2A1 and VEGFA expression are prognostic molecular biomarkers for patients with CRCLM with added value to established clinicopathological variables.
目的
在多机构队列的接受手术切除的结直肠癌肝转移（CRCLM）患者中，研究缺氧诱导因子1α（HIF1α）、溶质载体家族2成员1（SLC2A1）和血管内皮生长因子A（VEGFA）的个体及联合预后价值。
背景
在大多数CRCLM患者中，尽管手术切除目的是治愈，但似乎并非根治性的。缺氧诱导因子1α（HIF1α）、葡萄糖转运蛋白1（SLC2A1，也称为GLUT1）和VEGFA的过表达与结直肠癌（CRC）患者的肿瘤进展和不良预后相关。
方法
使用1990年至2010年间接受CRCLM切除患者的CRCLM组织及配对的原发性CRC制作组织芯片。通过免疫组织化学确定HIF1α、SLC2A1和VEGFA的预后价值。计算总生存的500倍交叉验证风险率比（HRRav）。
结果
分别在328、350和335例患者中评估了HIF1α、SLC2A1和VEGFA的表达。高SLC2A1表达与良好预后相关（HRRav，0.67；P（HRR>1）<0.01），高VEGFA表达与不良预后相关（HRRav，1.84；P（HRR<1）=0.02），在纳入既定临床病理预后变量的多因素分析后也是如此（HRRav分别为0.67；P（HRR>1）<0.01和HRRav，1.50；P（HRR<1）=0.02）。SLC2A1尤其在接受全身治疗的患者中显示出预后价值（P<0.01），而VEGFA表达的预后价值主要在未接受全身治疗的患者中观察到（P<0.01）。SLC2A1低表达且VEGFA高表达的患者预后尤其差（P<0.01）。HIF1α表达与生存无关。
结论
SLC2A1和VEGFA表达是CRCLM患者的预后分子生物标志物，对既定临床病理变量具有附加价值。
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