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18F-氟代脱氧葡萄糖摄取与结直肠癌中 KRAS/BRAF 突变的关系。

Relationship between 18F-fluorodeoxyglucose accumulation and KRAS/BRAF mutations in colorectal cancer.

机构信息

Department of Surgery, Kyoto University, Kyoto, Japan.

出版信息

Clin Cancer Res. 2012 Mar 15;18(6):1696-703. doi: 10.1158/1078-0432.CCR-11-1909. Epub 2012 Jan 26.

Abstract

PURPOSE

Positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) has been widely used in the management of colorectal cancer (CRC). However, the relationship between FDG accumulation and KRAS/BRAF mutations has not yet been investigated. The purpose of this study was to investigate whether KRAS/BRAF mutations affect FDG accumulation in CRC.

EXPERIMENTAL DESIGN

Retrospective analysis was conducted in 51 patients with CRC who underwent FDG-PET/computed tomographic (CT) scans for staging before primary tumor resection. The maximum standardized uptake value (SUV(max)) for the primary tumor and the tumor-to-liver ratio (TLR) were calculated from FDG accumulation and compared between KRAS/BRAF mutated and wild-type groups. Expression levels of glucose transporter-1 (GLUT1) and hexokinase type-II (HXK-II) were assessed by immunohistochemical analysis.

RESULTS

Both SUV(max) and TLR were significantly higher in the KRAS/BRAF-mutated group compared with the wild-type group (P = 0.006 and 0.001, respectively). Multivariate analysis indicated that SUV(max) and TLR remained significantly associated with KRAS/BRAF mutations (P = 0.016 and 0.01, respectively). KRAS/BRAF status could be predicted with an accuracy of 75% when a SUV(max) cutoff value of 13 or 14 was used. GLUT1 expression in cancer cells was positively correlated with FDG accumulation and KRAS/BRAF status whereas HXK-II expression was not.

CONCLUSION

FDG accumulation was higher in CRC with KRAS/BRAF mutations. FDG-PET/CT scans may be useful for predicting the KRAS/BRAF status of patients with CRC and thus aid in determination of therapeutic strategies for patients with CRC.

摘要

目的

正电子发射断层扫描(PET)结合(18)F-氟代脱氧葡萄糖(FDG)已广泛用于结直肠癌(CRC)的治疗管理。然而,FDG 积聚与 KRAS/BRAF 突变之间的关系尚未得到研究。本研究旨在探讨 KRAS/BRAF 突变是否影响 CRC 中 FDG 的积聚。

实验设计

对 51 例在原发肿瘤切除前接受 FDG-PET/计算机断层扫描(CT)分期的 CRC 患者进行回顾性分析。从 FDG 积聚中计算原发肿瘤的最大标准化摄取值(SUV(max))和肿瘤与肝脏的比值(TLR),并在 KRAS/BRAF 突变和野生型组之间进行比较。通过免疫组织化学分析评估葡萄糖转运蛋白-1(GLUT1)和己糖激酶 II(HXK-II)的表达水平。

结果

KRAS/BRAF 突变组的 SUV(max)和 TLR 均明显高于野生型组(P = 0.006 和 0.001)。多变量分析表明,SUV(max)和 TLR 与 KRAS/BRAF 突变仍显著相关(P = 0.016 和 0.01)。当 SUV(max)截断值为 13 或 14 时,KRAS/BRAF 状态的预测准确率为 75%。癌细胞中 GLUT1 的表达与 FDG 积聚和 KRAS/BRAF 状态呈正相关,而 HXK-II 的表达则无相关性。

结论

CRC 中 KRAS/BRAF 突变与 FDG 积聚增加有关。FDG-PET/CT 扫描可能有助于预测 CRC 患者的 KRAS/BRAF 状态,从而有助于确定 CRC 患者的治疗策略。

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