Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
Cancer Immunol Immunother. 2019 Aug;68(8):1369-1378. doi: 10.1007/s00262-019-02371-3. Epub 2019 Jul 23.
Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with poor prognosis. The evaluation of recurrence risk after liver resection is of great importance for ICCs. We aimed to assess the prognostic value of intra- and peritumoral immune infiltrations and to establish a novel histopathology-related immunoscore (HRI) associated with ICC recurrence. A total of 280 ICC patients who received curative resection between February 2005 and July 2011 were enrolled in our study. Patients were randomly assigned to the derivation cohort (n = 176) or the validation cohort (n = 104). Sixteen immune biomarkers in both intra- and peritumoral tissues were examined by immunohistochemistry. The least absolute shrinkage and selection operator (LASSO) Cox model was used to establish the HRI score. Cox regression analysis was used for multivariate analysis. Nine recurrence-related immune features were identified and integrated into the HRI score. The HRI score was used to categorize patients into low-risk and high-risk groups using the X-tile software. Kaplan-Meier analysis presented that the HRI score showed good stratification between low-risk and high-risk groups in both the derivation cohort (P < 0.001) and the validation cohort (P = 0.014), respectively. Multivariate analysis demonstrated that serum γ-glutamyl transpeptidase, carbohydrate antigen 19-9, lymphoid metastasis, tumor numbers, and the HRI score were independent risk factors associated with recurrence-free survival (RFS). The combination of Shen's model and HRI score provided better performance in recurrence prediction compared with traditional staging systems. The HRI score might serve as a promising RFS predictor for ICC with prognostic values.
肝内胆管细胞癌 (ICC) 是一种预后不良的罕见恶性肿瘤。评估肝切除术后的复发风险对 ICC 具有重要意义。我们旨在评估肿瘤内和肿瘤周围免疫浸润的预后价值,并建立与 ICC 复发相关的新型组织病理学相关免疫评分 (HRI)。共纳入 2005 年 2 月至 2011 年 7 月接受根治性切除术的 280 例 ICC 患者。患者被随机分配到推导队列(n=176)或验证队列(n=104)。通过免疫组织化学检测肿瘤内和肿瘤周围组织中的 16 种免疫标志物。最小绝对收缩和选择算子 (LASSO) Cox 模型用于建立 HRI 评分。Cox 回归分析用于多变量分析。确定了 9 个与复发相关的免疫特征,并将其整合到 HRI 评分中。使用 X-tile 软件,HRI 评分将患者分为低风险和高风险组。Kaplan-Meier 分析表明,HRI 评分在推导队列(P<0.001)和验证队列(P=0.014)中均能很好地区分低风险和高风险组。多变量分析表明,血清γ-谷氨酰转肽酶、糖链抗原 19-9、淋巴转移、肿瘤数量和 HRI 评分是与无复发生存 (RFS) 相关的独立危险因素。与传统分期系统相比,Shen 模型与 HRI 评分的组合在预测复发方面具有更好的性能。HRI 评分可能是 ICC 预后有价值的 RFS 预测因子。