Predictive role of circulatory HMGB1 in postoperative acute exacerbation of interstitial lung disease in lung cancer patients

AbstractPostoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29–11.70] ng/mL vs. 3.55 [2.07–5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.

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

10.21203/rs.3.rs-50646/v1 ◽

2020 ◽

Author(s):

Kakuhiro Yamaguchi ◽

Satoshi Nakao ◽

Hiroshi Iwamoto ◽

Atsushi Kagimoto ◽

Yoshinori Handa ◽

...

Keyword(s):

Lung Cancer ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Acute Exacerbation ◽

Scoring System ◽

Operative Time ◽

High Mobility ◽

Serum Levels ◽

Molecular Target ◽

Fatal Complication

Abstract 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.

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Value of immune factors for monitoring risk of lung cancer in patients with interstitial lung disease

Journal of International Medical Research ◽

10.1177/0300060519847403 ◽

2019 ◽

Vol 47 (7) ◽

pp. 3344-3353

Author(s):

Ning Li ◽

Haisheng Hu ◽

Ge Wu ◽

Baoqing Sun

Keyword(s):

Lung Cancer ◽

Interstitial Lung Disease ◽

Lung Disease ◽

Serum Levels ◽

Scaling Analysis ◽

Healthy Controls ◽

Healthy Individuals ◽

Reactive Protein ◽

Increased Risk ◽

Immune Factors

Objective Patients with interstitial lung disease (ILD) are at increased risk of developing lung cancer. We aimed to investigate the clinical significance of serum immune factors in this progression. Methods We retrospectively screened a hospital database from January 2012 to December 2016 for patients with lung cancer and ILD. We measured serum levels of C3, C4, IgA, IgG, IgM, C-reactive protein (CRP), ceruloplasmin (CER), and rheumatoid factor in these patients and in healthy controls. Results We analyzed data for 262 patients with lung cancer, 220 with ILD, and 57 healthy controls. CER levels were significantly higher in patients with lung cancer (0.35 ± 0.10 g/L) compared with both ILD patients (0.31 ± 0.25 g/L) and healthy individuals (0.25 ± 0.04 g/L). C3 and C4 levels were both significantly higher in healthy individuals compared with patients with lung cancer (C3: 1.70 ± 0.29 vs 1.04 ± 0.26 g/L, C4: 0.27 ± 0.24 vs 0.24 ± 0.09 g/L) and ILD (C3: 1.70 ± 0.29 vs 0.97 ± 0.25 g/L, C4: 0.27 ± 0.24 vs 0.21 ± 0.09 g/L). Optimal scaling analysis demonstrated that lung cancer was closely associated with CRP, CER, C3, and C4. Conclusions Increased levels of CRP and CER and decreased levels of C3 and C4 may identify patients with ILD at high risk of developing lung cancer.

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