Background

High-mobility group box 1 (HMGB1) is a pro-inflammatory protein, that is associated with tumorigenesis, interstitial lung disease (ILD), and acute lung injury. Chemotherapy-induced lung injury is a common and serious adverse event in patients with lung cancer and ILD, but its pathogenesis and predictive biomarkers are not known. This study aimed to investigate the predictive potential of serum HMGB1 levels for cytotoxic chemotherapy-induced lung injury in these patients.

Methods

From 743 patients with advanced lung cancer, we enrolled 83 consecutive patients with ILD and background-matched 83 patients without ILD. Additionally, 83 healthy subjects were included. After measuring baseline levels of serum HMGB1 in three groups, we evaluated the predictive values of baseline HMGB1 levels for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and ILD.

Results

Higher levels of serum HMGB1 were independently associated with higher tumor burden, as assessed by total tumor size, and the presence of ILD. Twenty-five (30.1%) of patients with lung cancer and ILD experienced cytotoxic chemotherapy-induced lung injury within one year. Univariate Cox proportional hazards model showed that higher levels of HMGB1 and higher tumor burden were associated with disease onset. Moreover, multivariate analysis revealed that only HMGB1 was independently associated with this severe complication in patients with lung cancer and ILD.

Conclusions

HMGB1 is a potential predictive blood biomarker for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and ILD. This study also suggests a potential pathogenesis of this serious adverse event that tumor- and ILD-derived HMGB1 accelerates lung injury.

中文翻译：

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血清高迁移率分组框1作为肺癌和间质性肺疾病患者的细胞毒性化学疗法诱发的肺损伤的预测指标。

背景

高迁移率族盒1（HMGB1）是一种促炎蛋白，与肿瘤发生，间质性肺病（ILD）和急性肺损伤有关。化学疗法诱发的肺损伤是肺癌和ILD患者的常见且严重的不良事件，但其发病机理和可预测的生物标志物尚不清楚。这项研究旨在调查血清HMGB1水平对这些患者的细胞毒性化学疗法诱导的肺损伤的预测潜力。

方法

从743名晚期肺癌患者中，我们招募了83位连续的ILD患者和背景匹配的83位无ILD的患者。另外，包括83名健康受试者。在测量了三组血清HMGB1的基线水平后，我们评估了基线HMGB1水平对肺癌和ILD患者的细胞毒性化学疗法诱发的肺损伤的预测价值。

结果

通过总肿瘤大小和ILD的存在评估，较高水平的血清HMGB1与较高的肿瘤负荷独立相关。一年之内，有25（30.1％）的肺癌和ILD患者经历了细胞毒性化学疗法诱发的肺损伤。单变量Cox比例风险模型显示，较高水平的HMGB1和较高的肿瘤负荷与疾病发作有关。此外，多变量分析显示，只有HMGB1与肺癌和ILD患者的这种严重并发症独立相关。

结论

HMGB1是潜在的预测性血液生物标志物，可用于肺癌和ILD患者的细胞毒性化疗诱导的肺损伤。这项研究还表明，这种严重不良事件的潜在发病机制可能是肿瘤和ILD衍生的HMGB1加速肺损伤。