Serum high-mobility group box 1 as a predictive marker for cytotoxic chemotherapy-induced lung injury in patients with lung cancer and interstitial lung disease. (October 2020)

• Record Type: Journal Article
• Authors: Nakao, Satoshi; Yamaguchi, Kakuhiro; Iwamoto, Hiroshi; Sakamoto, Shinjiro; Horimasu, Yasushi; Masuda, Takeshi; Miyamoto, Shintaro; Nakashima, Taku; Ohshimo, Shinichiro; Fujitaka, Kazunori; Hamada, Hironobu; Hattori, Noboru
• Is Part Of: Respiratory medicine. Volume 172(2020)
• Publication Date: 2020-10
• Subjects: Lung cancer -- Interstitial lung disease -- Lung injury -- High-mobility group box 1 -- Soluble receptor for advanced glycation end products -- Biomarker; ALAT Latin American Thoracic Association -- ATS American Thoracic Society -- AUC area under the curve -- CT computed tomography -- ERS European Respiratory Society -- FVC forced vital capacity -- HMGB1 high-mobility group box 1 -- ILD interstitial lung disease -- IPF idiopathic pulmonary fibrosis -- IQR interquartile range -- JRS Japanese Respiratory Society -- PS performance status -- RAGE receptor for advanced glycation end products -- RECIST Response Evaluation Criteria in Solid Tumors -- ROC receiver operating characteristic -- sRAGE soluble receptor for advanced glycation end products -- UIP usual interstitial pneumonia; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2020.106131
• Languages: English
• ISSNs: 0954-6111

Abstract

Abstract: 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. Highlights: HMGB1 is an inflammatory protein associated with lung cancer and lung injury. Lung injury by chemotherapy is common in lung cancer with interstitial lung disease. Elevated HMGB1 levels may be the first blood marker to predict this adverse event. Interstitial lung disease may be a risk factor of the disease by increasing HMGB1. Tumor burden also contributes to disease development by increasing HMGB1.