Systemic inflammation and insulin resistance-related indicator predicts poor outcome in patients with cancer cachexia

IF 6 3区医学 Q1 CELL BIOLOGY

Cancer & Metabolism Pub Date : 2024-01-25 DOI:10.1186/s40170-024-00332-8

Guo-Tian Ruan, Li Deng, Hai-Lun Xie, Jin-Yu Shi, Xiao-Yue Liu, Xin Zheng, Yue Chen, Shi-Qi Lin, He-Yang Zhang, Chen-An Liu, Yi-Zhong Ge, Meng-Meng Song, Chun-Lei Hu, Xiao-Wei Zhang, Ming Yang, Wen Hu, Ming-Hua Cong, Li-Chen Zhu, Kun-Hua Wang, Han-Ping Shi

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Abstract

The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13–1.33), 34% (internal test cohort, 95%CI = 1.11–1.62), and 35% (external validation cohort, 95%CI = 1.14–1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22–1.71; internal test cohort, HR = 1.62, 95%CI = 1.12–2.36; external validation cohort, HR = 1.61, 95%CI = 1.15–2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05–4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42–3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52–4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24–2.55] in patients with cancer cachexia. The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

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全身炎症和胰岛素抵抗相关指标可预测癌症恶病质患者的不良预后

C反应蛋白（CRP）-甘油三酯-葡萄糖（TyG）指数（CTI）是一种代表炎症和胰岛素抵抗（IR）水平的指标，与癌症的不良预后有关；然而，CTI尚未在癌症恶病质患者中得到验证。因此，本研究旨在探索 CTI 在癌症恶病质患者中的潜在临床价值。在这项研究中，我们的前瞻性多中心队列纳入了 1411 名癌症恶病质患者（平均年龄为 59.45±11.38 岁，63.3% 为男性），并对多种癌症类型进行了综合分析。我们随机抽取了 30% 的患者作为内部测试队列（平均年龄为 58.90 ± 11.22，男性占 61.4%）。此外，我们还将 307 名癌症恶病质患者纳入外部验证队列（平均年龄为 61.16 ± 11，58.5% 为男性）。为研究 CTI 的预后价值，我们绘制了接收者操作特征曲线（ROC）和校准曲线。CTI 的预后价值还通过单变量和多变量生存分析法进行了研究。生存曲线显示，CTI 在全部、内部和外部验证队列中均显示出显著的预后价值。预后 ROC 曲线和校准曲线显示，CTI 在预测癌症恶病质患者的生存期方面表现出良好的一致性。多变量生存分析表明，CTI 标准差每增加一个百分点，死亡风险就会增加 22%（总体队列，95% 置信区间 [CI] = 1.13-1.33）、34%（内部测试队列，95%CI = 1.11-1.62）和 35%（外部验证队列，95%CI = 1.14-1.59）。高 CTI 可可靠地预测较短的生存期（总体队列，危险比 [HR] = 1.45，95%CI = 1.22-1.71；内部测试队列，HR = 1.62，95%CI = 1.12-2.36；外部验证队列，HR = 1.61，95%CI = 1.15-2.26）。在不同的肿瘤亚组中，高CTI可明显预测较短的生存期，如食管癌[HR = 2.11, 95%CI = 1.05-4.21]和结直肠癌[HR = 2.29, 95%CI = 1.42-3.71]。中介效应分析发现，PGSGA、ECOG PS 和 EORTC QLQ-C30 对 CTI 直接效应的中介比例分别为 21.72%、19.63% 和 11.61%。我们发现，CTI 与癌症恶病质患者 90 天[HR = 2.48，95%CI = 1.52-4.14]和 180 天死亡率[HR = 1.77，95%CI = 1.24-2.55]之间存在显著正相关。CTI 可以预测癌症恶病质患者的短期和长期生存期，为临床实践提供了有用的预后工具。

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来源期刊

Cancer & Metabolism Multiple-

自引率

1.70%

发文量

审稿时长

14 weeks

期刊介绍： Cancer & Metabolism welcomes studies on all aspects of the relationship between cancer and metabolism, including: -Molecular biology and genetics of cancer metabolism -Whole-body metabolism, including diabetes and obesity, in relation to cancer -Metabolomics in relation to cancer; -Metabolism-based imaging -Preclinical and clinical studies of metabolism-related cancer therapies.