Higher circulatory HMGB1 accelerates postoperative acute exacerbation of interstitial lung disease in lung cancer

Background: Postoperative acute exacerbation of interstitial lung disease (AE-ILD) is a fatal complication in patients with lung cancer and ILD, and it needs to be overcome to improve the long-term outcomes of these patients. However, the molecular target for predicting and preventing this fatal complication remains unclear. High-mobility group box 1 (HMGB1), which is reported to increase due to surgical procedure, activates a pro-inflammatory response associated with acute lung injury. This study aimed to elucidate the association between postoperative AE-ILD and circulatory HMGB1, especially focusing on its predictive potential. Methods: This study included 152 patients with lung cancer and ILD, who underwent radical surgery between January 2011 and August 2019. We measured HMGB1 serum levels, and investigated the factors affecting HMGB1 and the predictive potential of HMGB1 for postoperative AE-ILD.Results: Postoperative AE-ILD was developed in 17 (11.2%) of 152 patients with lung cancer and ILD. HMGB1 serum levels in patients with AE-ILD were significantly higher than those in patients without (median [IQR]: 5.39 [3.29-11.70] ng/mL vs 3.55 [2.07-5.62] ng/mL). Logistic regression analysis revealed that HMGB1 higher levels and longer operative time was independently associated with a higher incidence of postoperative AE-ILD. Furthermore, when HMGB1 and operative time were incorporated into previously reported risk scoring system, the concordance index was 0.876 which is statistically higher than 0.715 calculated by reported scoring system only.Conclusions: Baseline levels of serum HMGB1 could be a promising biomarker for predicting postoperative AE-ILD, especially when combined with operative time. HMGB1 may be a molecular target of this fatal complication to be overcome.