Department of Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto, Japan.
Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
J Transl Med. 2018 Apr 11;16(1):95. doi: 10.1186/s12967-018-1475-x.
Surgical resection remains the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). Prognosis after surgery is unsatisfactory despite improvements in treatment and post-operative clinical management. Despite developments in the molecular profiling of ICC, the preoperative prediction of prognosis remains a challenge. This study aimed to identify clinical prognostic indicators by investigating the molecular profiles of ICC and evaluating the preoperative imaging data of F-fluorodeoxyglucose positron emission tomography (F-FDG-PET).
A retrospective analysis was performed on 50 consecutive patients with ICC who underwent curative hepatectomy after F-FDG-PET examination. To evaluate the molecular profiles of ICC, KRAS mutation status was assessed in resected specimens. For the assessment of glucose uptake, we observed the expression of glucose transporter-1 (GLUT-1) by immunohistochemistry. The data of F-FDG-PET were re-evaluated as follows: maximum standardized uptake value, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Cut-off values were determined using receiver operating characteristic (ROC) curve analysis. Cumulative overall survival (OS) was analyzed using the Kaplan-Meier analysis.
Overall, 16 (32.0%) patients had mutations in KRAS. Patients with mutated KRAS exhibited shorter OS than those with wild-type KRAS (5-year OS, 0% vs. 35.1%, P < 0.001). GLUT-1 expression was significantly higher in tumors with mutated KRAS than in tumors with wild-type KRAS (median, 4.0 vs. 1.0, P < 0.001). Survival was significantly different when stratified by expression of GLUT-1 (5-year OS, 0% vs. 46.5%, P <0.001). Among the F-FDG-PET parameters, the MTV and TLG were significantly higher in the mutated KRAS group than in the wild-type KRAS group (P = 0.013 and P = 0.026, respectively). ROC curve analysis revealed a cut-off value of 38 for the MTV, with the highest accuracy (area under the curve = 0.789; 95% confidence interval, 0.581-0.902) for predicting KRAS mutation. This cut-off value permitted stratification of OS (high vs. low: 5-year OS, 13.1% vs. 36.7%, P = 0.008).
High MTV is associated with KRAS mutation and poor postoperative outcomes in patients with ICC, suggesting that the MTV of ICC measured by F-FDG-PET may provide useful information for tumor molecular profiles and prognosis.
手术切除仍然是治疗肝内胆管癌（ICC）的主要方法。尽管治疗和术后临床管理有所改善，但手术后的预后仍不理想。尽管 ICC 的分子特征分析取得了进展，但术前预测预后仍然是一个挑战。本研究旨在通过研究 ICC 的分子特征并评估 F-氟脱氧葡萄糖正电子发射断层扫描（F-FDG-PET）的术前影像学数据来确定临床预后指标。
对 50 例连续接受 F-FDG-PET 检查后行根治性肝切除术的 ICC 患者进行回顾性分析。为了评估 ICC 的分子特征，我们评估了切除标本中 KRAS 突变状态。通过免疫组织化学观察葡萄糖转运蛋白-1（GLUT-1）的表达来评估葡萄糖摄取。重新评估 F-FDG-PET 的数据如下：最大标准化摄取值、代谢肿瘤体积（MTV）和总病灶糖酵解（TLG）。使用接收者操作特征（ROC）曲线分析确定截断值。使用 Kaplan-Meier 分析分析累积总生存率（OS）。
总体而言，16 例（32.0%）患者的 KRAS 发生突变。KRAS 突变患者的 OS 明显短于 KRAS 野生型患者（5 年 OS，0% vs. 35.1%，P<0.001）。KRAS 突变型肿瘤中 GLUT-1 的表达明显高于 KRAS 野生型肿瘤（中位数，4.0 与 1.0，P<0.001）。根据 GLUT-1 的表达进行分层时，生存情况有显著差异（5 年 OS，0% vs. 46.5%，P<0.001）。在 F-FDG-PET 参数中，KRAS 突变组的 MTV 和 TLG 明显高于 KRAS 野生型组（P=0.013 和 P=0.026）。ROC 曲线分析显示 MTV 的截断值为 38，准确性最高（曲线下面积=0.789；95%置信区间，0.581-0.902），可预测 KRAS 突变。该截断值可对 OS 进行分层（高 vs. 低：5 年 OS，13.1% vs. 36.7%，P=0.008）。
ICC 中 MTV 较高与 KRAS 突变和术后不良结局相关，提示 F-FDG-PET 测量的 ICC MTV 可能为肿瘤分子特征和预后提供有用信息。
