Prognostic significance of combined fibrinogen concentration and neutrophil-to-lymphocyte ratio in patients with resectable non-small cell lung cancer

Abstract

Objective: Cancer-associated inflammation and coagulation cascades play vital roles in cancer progression and survival. In this study, we investigated the significance of the combination of preoperative fibrinogen and the neutrophil-to-lymphocyte ratio (NLR) in predicting the survival of patients with non-small cell lung cancer (NSCLC).

Methods: We retrospectively enrolled 589 patients with NSCLC who underwent surgery. The univariate and multivariate Cox survival analyses were used to evaluate the prognostic indicators, including the combination of fibrinogen and NLR (F-NLR). The cut-off values for fibrinogen, NLR, and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis. According to the ROC curve, the recommended cut-off values for fibrinogen and the NLR were 3.48 g/L and 2.30, respectively. Patients with both a high NLR (≥ 2.30) and hyperfibrinogenemia (≥ 3.48 g/L) were given a score of 2, whereas those with one or neither were scored as 1 or 0, respectively.

Results: Our results showed that F-NLR was an independent prognostic indicator for disease-free survival (DFS) [hazard ratio (HR), 1.466; 95% confidence interval (CI), 1.243-1.730; P < 0.001] and overall survival (OS) (HR, 1.512; 95% CI, 1.283-1.783; P < 0.001). The five-year OS rates were 66.1%, 53.5%, and 33.3% for the F-NLR = 0, F-NLR = 1, and F-NLR = 2, respectively ( P < 0.001). Correspondingly, their five-year DFS rates were 62.2%, 50.3%, and 30.4%, respectively ( P < 0.001). In the subgroup analyses of the pathological stages, the F-NLR level was significantly correlated with DFS and OS in stage I and IIIA cancers.

Conclusions: Preoperative F-NLR score can be used as a valuable prognostic marker for patients with resectable early-stage NSCLC.

Keywords: Non-small cell lung cancer; fibrinogen; prognosis; neutrophil-to-lymphocyte ratio.

1

Survival curves of patients with non-small cell lung cancer (NSCLC) (stages I-IIIA) in the combination of fibrinogen and neutrophil-to-lymphocyte ratio (F-NLR). (A) Disease-free survival (DFS) curve of patients with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P > 0.001). (B) Overall survival (OS) curve of patients with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P > 0.001).

2

Survival curves of patients with NSCLC (stage I-IIIA) in F-NLR. (A) DFS curve of patients with stage I NSCLC with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P > 0.001). (B) OS curve of patients with stage I NSCLC with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P > 0.001). (C) DFS curve of patients with stage II NSCLC with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P = 0.149). (D) OS curve of patients with stage II NSCLC with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P = 0.139). (E) DFS curve of patients with stage IIIA NSCLC with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P = 0.001). (F) OS curve of patients with stage IIIA NSCLC with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P > 0.001).

3

Survival curves of patients with adenocarcinoma or squamous carcinoma in F-NLR. (A) DFS curve of patients with adenocarcinoma with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P > 0.001). (B) OS curve of patients with adenocarcinoma with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P > 0.001). (C) DFS curve of patients with squamous carcinoma with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P > 0.001). (D) OS curve of patients with squamous carcinoma with F-NLR=0, F-NLR=1, and F-NLR=2 (log-rank test, P > 0.001).