Hao Xiaohe, Zhang Zhenyu, Kong Jing, Ma Rufei, Mao Cuiping, Peng Xun, Ru Kun, Liu Lisheng, Zhao Chuanxi, Mo Xinkai, Cai Meijuan, Yu Xiangguo, Lin Qinghai
Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, 440 Ji-Yan Road, Jinan, Shandong Province, 250117, PR China.
Department of Cardiology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, China.
Cardiooncology. 2024 Sep 4;10(1):56. doi: 10.1186/s40959-024-00263-9.
Cardiovascular toxicity represents a significant adverse consequence of cancer therapies, yet there remains a paucity of effective biomarkers for its timely monitoring and diagnosis. To give a first evidence able to elucidate the role of Growth Differentiation Factor 15 (GDF15) in the context of cancer diagnosis and its specific association with cardiac indicators in cancer patients, thereby testing its potential in predicting the risk of CTRCD (cancer therapy related cardiac dysfunction).
Analysis of differentially expressed genes (DEGs), including GDF15, was performed by utilizing data from the public repositories of the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cardiomyopathy is the most common heart disease and its main clinical manifestations, such as heart failure and arrhythmia, are similar to those of CTRCD. Examination of GDF15 expression was conducted in various normal and cancerous tissues or sera, using available database and serum samples. The study further explored the correlation between GDF15 expression and the combined detection of cardiac troponin-T (c-TnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), assessing the combined diagnostic utility of these markers in predicting risk of CTRCD through longitudinal electrocardiograms (ECG).
GDF15 emerged as a significant DEG in both cancer and cardiomyopathy disease models, demonstrating good diagnostic efficacy across multiple cancer types compared to healthy controls. GDF15 levels in cancer patients correlated with the established cardiac biomarkers c-TnT and NT-proBNP. Moreover, higher GDF15 levels correlated with an increased risk of ECG changes in the cancer cohort.
GDF15 demonstrated promising diagnostic potential in cancer identification; higher GDF15, combined with elevated cardiac markers, may play a role in the monitoring and prediction of CTRCD risk.
心血管毒性是癌症治疗的一个重大不良后果，但目前仍缺乏用于及时监测和诊断的有效生物标志物。为了首次提供证据，阐明生长分化因子15（GDF15）在癌症诊断中的作用及其与癌症患者心脏指标的特定关联，从而测试其预测癌症治疗相关心脏功能障碍（CTRCD）风险的潜力。
利用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的公开数据，对包括GDF15在内的差异表达基因（DEG）进行分析。心肌病是最常见的心脏病，其主要临床表现，如心力衰竭和心律失常，与CTRCD相似。利用现有数据库和血清样本，对GDF15在各种正常和癌组织或血清中的表达进行检测。该研究进一步探讨了GDF15表达与心肌肌钙蛋白T（c-TnT）和脑钠肽前体N端（NT-proBNP）联合检测之间的相关性，通过纵向心电图（ECG）评估这些标志物在预测CTRCD风险方面的联合诊断效用。
GDF15在癌症和心肌病疾病模型中均为显著的差异表达基因，与健康对照相比，在多种癌症类型中显示出良好的诊断效能。癌症患者的GDF15水平与已确立的心脏生物标志物c-TnT和NT-proBNP相关。此外，在癌症队列中，较高的GDF15水平与心电图改变风险增加相关。
GDF15在癌症识别中显示出有前景的诊断潜力；较高的GDF15水平与升高的心脏标志物相结合，可能在CTRCD风险的监测和预测中发挥作用。
