BackgroundImmune function, nutrition status, and inflammation influence tumor initiation and progression. This was a retrospective multicenter cohort study that investigated the prognostic value and clinical relevance of immune-, inflammatory-, and nutritional-related biomarkers to develop a novel prognostic immune–inflammatory–nutritional score (PIIN score) for patients with intrahepatic cholangiocarcinoma (ICC).MethodsThe clinical data of 571 patients (406 in the training set and 165 in the validation set) were collected from four large hepato-pancreatico-biliary centers of patients with ICC who underwent surgical resection between January 2011 and September 2017. Twelve blood biomarkers were collected to develop the PIIN score using the LASSO Cox regression model. The predictive value was further assessed using validation datasets. Afterward, nomograms combining the PIIN score and other clinicopathological parameters were developed and validated based on the calibration curve, time-dependent AUC curves, and decision curve analysis (DCA). The primary outcomes evaluated were overall survival (OS) and recurrence-free survival (RFS) from the day of primary resection of ICC.ResultsBased on the albumin–bilirubin (ALBI) grade, neutrophil- to- lymphocyte ratio (NLR), prognostic nutritional index (PNI), and systemic immune- inflammation index (SII) biomarkers, the PIIN score that classified patients into high-risk and low-risk groups could be calculated. Patients with high-risk scores had shorter OS (training set, p < 0.001; validation set, p = 0.003) and RFS (training set, p < 0.001; validation set, p = 0.002) than patients with low-risk scores. The high PIIN score was also associated with larger tumors (≥5 cm), lymph node metastasis (N1 stage), multiple tumors, and high tumor grade or TNM (tumor (T), nodes (N), and metastases (M)) stage. Furthermore, the high PIIN score was a significant independent prognostic factor of OS and RFS in both the training (p < 0.001) and validation (p = 0.003) cohorts, respectively. A PIIN-nomogram for individualized prognostic prediction was constructed by integrating the PIIN score with the clinicopathological variables that yielded better predictive performance than the TNM stage.ConclusionThe PIIN score, a novel immune–inflammatory–nutritional-related prognostic biomarker, predicts the prognosis in patients with resected ICC and can be a reliable tool for ICC prognosis prediction after surgery. Our study findings provide novel insights into the role of cancer-related immune disorders, inflammation, and malnutrition.

中文翻译：

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用于预测肝内胆管癌根治性切除术后结果的新预后免疫-炎症-营养评分的开发和验证：一项多中心研究

背景免疫功能、营养状况和炎症影响肿瘤的发生和发展。这是一项回顾性多中心队列研究，旨在调查免疫、炎症和营养相关生物标志物的预后价值和临床相关性，以开发针对肝内胆管癌 (ICC) 患者的新型预后免疫-炎症-营养评分（PIIN 评分）方法 收集 2011 年 1 月至 2017 年 9 月期间来自四家大型肝胰胆管中心接受手术切除的 ICC 患者的 571 名患者（训练集 406 名和验证集 165 名）的临床数据。12 种血液生物标志物收集使用 LASSO Cox 回归模型开发 PIIN 分数。使用验证数据集进一步评估预测值。之后，基于校准曲线、时间依赖性 AUC 曲线和决策曲线分析 (DCA)，开发并验证了结合 PIIN 评分和其他临床病理学参数的列线图。评估的主要结果是自 ICC 初次切除之日起的总生存期 (OS) 和无复发生存期 (RFS)。指数 (PNI) 和全身免疫炎症指数 (SII) 生物标志物，可以计算将患者分为高风险和低风险组的 PIIN 评分。与低风险评分患者相比，高风险评分患者的 OS（训练集，p < 0.001；验证集，p = 0.003）和 RFS（训练集，p < 0.001；验证集，p = 0.002）更短. 高 PIIN 评分还与较大的肿瘤 (≥5 cm)、淋巴结转移（N1 期）、多发肿瘤和高肿瘤分级或 TNM（肿瘤 (T)、淋巴结 (N) 和转移 (M)）相关阶段。此外，高 PIIN 评分分别是训练 (p < 0.001) 和验证 (p = 0.003) 队列中 OS 和 RFS 的重要独立预后因素。通过将 PIIN 评分与临床病理变量相结合，构建了用于个体化预后预测的 PIIN 列线图，其预测性能优于 TNM 分期。结论 PIIN 评分是一种新型免疫-炎症-营养相关的预后生物标志物，可预测患者的预后与切除的 ICC，可以成为 ICC 手术后预后预测的可靠工具。