Liang Yuxin, Zhang Zilong, Zhong Deyuan, Lai Chunyou, Dai Zonglin, Zou Haibo, Feng Tianhang, Shang Jin, Shi Ying, Huang Xiaolun
Department of Hepatobiliary-Pancreatic Surgery, Cell Transplantation Center, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Clinical Immunology Translational Medicine Key Laboratory of Sichuan Province and Organ Transplant Research Institute, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Front Oncol. 2022 Aug 9;12:913731. doi: 10.3389/fonc.2022.913731. eCollection 2022.
Inflammation, immunity, and nutrition status play important roles in tumorigenesis, progression, and metastasis. This study aimed to evaluate the prognostic value of Inflammation-Immunity-Nutrition Score (IINS) for overall survival (OS) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC) undergoing radical surgery.
A total of 204 HCC patients who met the criteria were included in this retrospective study: 144 in the prediction model and 60 in the validation model. IINS was constructed based on the sum of classification scores of preoperative high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The associations between the IINS group and the clinicopathologic characteristics were analyzed using Pearson's χ2 test or Fisher's exact test. Multivariate Cox regression analysis was used to evaluate variables significant on univariate analysis. Kaplan-Meier survival curves were conducted to investigate the prognostic values of IINS, Alpha-fetoprotein (AFP) and IINS-AFP classification. The prognostic performances of all the potential prognostic factors were further compared by receiver operating characteristic (ROC) curve, and time-dependent ROC curve. The internal validation and external validation were used to ensure the credibility of this prediction model.
The patients were divided into low and high IINS groups according to the median of IINS. According to multivariate Cox regression analyses, the Barcelona Clinic Liver Cancer (BCLC) Stage (P=0.003), AFP (P=0.013), and IINS (P=0.028) were independent prognostic factors for OS, and BCLC Stage (P=0.009), microvascular invasion (P=0.030), and IINS (P=0.031) were independent prognostic factors for PFS. High IINS group were associated with significantly worse OS and PFS compared with low IINS group (P<0.001; P=0.004). In terms of clinical prognosis, IINS-AFP classification was good in group I, moderate in group II, and poor in group III. Group I had a longer OS (P<0.001) and PFS (P=0.008) compared with group II and III. ROC analysis revealed that IINS-AFP classification had a better prognostic performance for OS (AUC: 0.767) and PFS (AUC: 0.641) than other predictors, excluding its slightly lower predictive power for PFS than IINS. The time-dependent ROC curves also showed that both IINS (12-month AUC: 0.650; 24-month AUC: 0.670; 36-month AUC: 0.880) and IINS-AFP classification (12-month AUC: 0.720; 24-month AUC: 0.760; 36-month AUC: 0.970) performed well in predicting OS for HCC patients. Furthermore, the internal validation and external validation proved that IINS had good predictive performance, strong internal validity and external applicability, and could be used to establish the prediction model.
Inflammation-immunity-nutrition score could be a powerful clinical prognostic indicator in HCC patients undergoing radical surgery. Furthermore, IINS-AFP classification presents better prognostic performance than IINS or AFP alone, and might serve as a practical guidance to help patients adjust treatment and follow-up strategies to improve future outcomes.
炎症、免疫和营养状况在肿瘤发生、发展和转移中发挥着重要作用。本研究旨在评估炎症 - 免疫 - 营养评分（IINS）对接受根治性手术的肝细胞癌（HCC）患者总生存期（OS）和无进展生存期（PFS）的预后价值。
本回顾性研究共纳入204例符合标准的HCC患者：144例纳入预测模型，60例纳入验证模型。IINS基于术前高敏C反应蛋白（hsCRP）、淋巴细胞（LYM）和白蛋白（ALB）的分类评分总和构建。使用Pearson卡方检验或Fisher精确检验分析IINS组与临床病理特征之间的关联。采用多因素Cox回归分析评估单因素分析中有意义的变量。绘制Kaplan - Meier生存曲线以研究IINS、甲胎蛋白（AFP）和IINS - AFP分类的预后价值。通过受试者工作特征（ROC）曲线和时间依赖性ROC曲线进一步比较所有潜在预后因素的预后性能。采用内部验证和外部验证以确保该预测模型的可信度。
根据IINS的中位数将患者分为IINS低分组和高分组。多因素Cox回归分析显示，巴塞罗那临床肝癌（BCLC）分期（P = 0.003）、AFP（P = 0.013）和IINS（P = 0.028）是OS的独立预后因素，BCLC分期（P = 0.009）、微血管侵犯（P = 0.030）和IINS（P = 0.031）是PFS的独立预后因素。与IINS低分组相比，IINS高分组的OS和PFS明显更差（P < 0.001；P = 0.004）。在临床预后方面，IINS - AFP分类在I组良好，II组中等，III组较差。与II组和III组相比（P < 0.001），I组的OS更长（P < 0.001），PFS更长（P = 0.008）。ROC分析显示，IINS - AFP分类对OS（AUC：0.767）和PFS（AUC：0.641）的预后性能优于其他预测指标，但对PFS的预测能力略低于IINS。时间依赖性ROC曲线还显示，IINS（12个月AUC：0.650；24个月AUC：0.670；36个月AUC：0.880）和IINS - AFP分类（12个月AUC：0.720；24个月AUC：0.760；36个月AUC：0.970）在预测HCC患者OS方面表现良好。此外，内部验证和外部验证证明IINS具有良好的预测性能、强大的内部有效性和外部适用性，可用于建立预测模型。
炎症 - 免疫 - 营养评分可能是接受根治性手术的HCC患者强有力的临床预后指标。此外，IINS - AFP分类比单独的IINS或AFP具有更好的预后性能，可能为帮助患者调整治疗和随访策略以改善未来结局提供实用指导。
