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Serum S100 calcium-binding protein A4 as a novel predictive marker of acute exacerbation of interstitial pneumonia after surgery for lung cancer.

ABSTRACT:

Background

Acute exacerbation (AE) of interstitial pneumonia (IP) is the most fatal complication after lung resection for lung cancer. To improve the prognosis of lung cancer with IP, the risk factors of AE of IP after lung resection should be assessed. S100 calcium-binding protein A4 (S100A4) is a member of the S100 family of proteins and is a known marker of tissue fibrosis. We examined the usefulness of S100A4 in predicting AE of IP after lung resection for lung cancer.

Methods

This study included 162 patients with IP findings on preoperative high-resolution computed tomography scan who underwent curative-intent lung resection for primary lung cancer between April 2007 and March 2019. Serum samples were collected preoperatively. Resected lung tissue from 76 patients exhibited usual IP (UIP) pattern in resected lung were performed immunohistochemistry (IHC). Relationship between S100A4 and the incidence of AE of IP and short-term mortality was analyzed.

Results

The receiver operating characteristic area under the curve for serum S100A4 to predict postoperative AE of IP was 0.871 (95% confidence interval [CI], 0.799-0.943; P < 0.001), with a sensitivity of 93.8% and a specificity of 75.3% at the cutoff value of 17.13 ng/mL. Multivariable analysis revealed that a high serum S100A4 level (> 17.13 ng/mL) was a significant risk factor for AE of IP (odds ratio, 42.28; 95% CI, 3.98-449.29; P = 0.002). A 1-year overall survival (OS) was significantly shorter in patients with high serum levels of S100A4 (75.3%) than in those with low serum levels (92.3%; P = 0.003). IHC staining revealed that fibroblasts, lymphocytes, and macrophages expressed S100A4 in the UIP area, and the stroma and fibrosis in the primary tumor expressed S100A4, whereas tumor cells did not.

Conclusions

Serum S100A4 had a high predictive value for postoperative AE of IP and short-term mortality after lung resection.

SUBMITTER: Kagimoto A

PROVIDER: S-EPMC8173829 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectivesTo assess clinical, laboratory and radiographic findings associated with outcomes and to clarify more practical ways to predict hospital mortality in patients with acute exacerbation (AE) of chronic fibrosing interstitial pneumonia (CFIP).DesignSingle-centre retrospective cohort study.SettingUniversity Hospital in Japan.ParticipantsWe identified 51 consecutive patients with AE of idiopathic CFIP through multidisciplinary discussion. Patients who had connective tissue disease, drug-induced lung disease, pneumoconiosis, hypersensitivity pneumonitis, sarcoidosis, pulmonary histiocytosis, lymphangioleiomyomatosis and eosinophilic pneumonia were excluded.InterventionsThere were no interventions.Main outcome measuresThe main outcome was determination of in-hospital mortality predictors. Other outcomes included clinical, laboratory and radiographic differences between non-survivors and survivors in patients with AE of CFIP.ResultsThe mean age of the patients with AE of CFIP was 71 years. Compared with survivors, non-survivors had a significantly shorter duration of symptoms before admission, lower prevalence of peripheral distribution of ground-glass opacity and centrilobular emphysema (CLE) on thin-section CT, lower peripheral lymphocyte count, higher brain natriuretic peptide titre, lower Pao2:Fio2 (P:F) ratio, higher prevalence of systemic inflammatory response syndrome (SIRS) and higher SIRS score on admission (p=0.0069, 0.0032, 0.015, 0.040, 0.0098, 0.012, 9.9×10(-7) and 5.4×10(-6), respectively). Multivariate analysis revealed SIRS (HR=6.2810, p=0.015), CLE (HR=0.0606, p=3.6×10(-5)) and serum procalcitonin level (HR=2.7110, p=0.022) to be independent predictors of in-hospital mortality. A Kaplan-Meier estimate on the basis of stratification according to the presence or absence of SIRS and CLE demonstrated a distinct survival curve for each subset of patients.ConclusionsDistinct survival curves documented by stratification according to the presence or absence of SIRS and CLE may provide basic information for a rational management strategy for patients with AE of CFIP on admission.