Albumin-to-fibrinogen ratio as a promising biomarker to predict clinical outcome of non-small cell lung cancer individuals

Abstract

Chronic inflammation is one of the critical causes to promote the initiation and metastasis of solid malignancies including lung cancer (LC). Here, we aimed to investigate the prognostic roles of albumin (Alb)-to-fibrinogen (Fib) ratio (AFR), Fib and Alb in LC and to establish a novel effective nomogram combined with AFR. Four hundred twelve LC patients diagnosed between February 2005 and December 2014 were recruited in this prospective study. The prognostic roles of AFR, Fib, Alb, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) were identified by X-tile software, Kaplan-Meier curve, Cox regression model, and time-dependent ROC. Pretreatment high circulating Fib, low AFR, and Alb were significantly associated with increased risk of death for LC patients, especially for non-small cell lung cancer (NSCLC) patients in all stages. The area under curves (AUCs) of AFR, Fib, and NLR were higher than them within Alb and PLR for predicting the survival of NSCLC patients. Moreover, we found that clinical outcome of high AFR patient with chemo-radiotherapy was superior to low AFR patient; overall survival rate of stage II-III NSCLC patients undergoing chemo-radiotherapy was significantly lower than the surgical patients with treatment of adjuvant chemo-radiotherapy(P = 0.001) in low AFR subgroup. On the contrary, clinical outcome of the patients receiving chemo-radiotherapy was the same to the patients undergoing surgery and adjuvant chemo-radiotherapy (P = 0.405) in high AFR subgroup. In addition, c-index of predicted nomogram including AFR (0.717) for NSCLC patients with treatment of chemo-radiotherapy was higher than that without AFR (0.707). Our findings demonstrated that circulating pretreatment AFR might be a potential biomarker to predict clinical efficacy of surgical resection and adjuvant chemo-radiotherapy and be a prognostic biomarker for NSCLC individuals.

Keywords: Albumin-to-fibrinogen ratio; nomogram; non-small cell lung cancer; prognosis.

Figure 1

The optimal cut‐off value of preoperative circulating Alb to Fib ratio (A–C), Fib (D–F), and Alb (G–I) in 412 LC patients using X‐tile software. (A, D, G) The data were represented graphically in a right‐triangular grid where each point represents the data from a given set of divisions. The plots showed the χ ² log‐rank values produced, dividing them into three or two groups by the cut‐off point. The optimal cut‐points (7.80, 3.30, and 39.00, respectively) were determined by locating the brightest pixel on the X‐tile plot. The distribution of number of patients was shown on the histogram (B, E, H) and corresponding populations were displayed on the Kaplan–Meier curve (C, F, I), respectively.

Figure 2

Kaplan–Meier curves of AFR, Fib, and Alb for 3 years’ OS in NSCLC patients. In NSCLC patients: (A) AFR, (B) Fib and (C) Alb; in stage I–III NSCLC subgroups: (D) AFR, (E) Fib and (F) Alb; in stage IV NSCLC subgroups: (G) AFR, (H) Fib and (I) Alb.

Figure 3

Cox regression forest plot of circulating inflammatory biomarkers in each subgroup. HR, hazard ratio; CI, confidence interval.

Figure 4

The correlation of prognostic parameters with clinical characteristics and comparison of prognostic parameters in NSCLC patients. (A) the relationship between tumor size and AFR in NSCLC; (B and C) the relationship between tumor stage and NLR and PLR in NSCLC; (D) time‐dependent ROC analysis of pretreatment circulating AFR, Fib, Alb, NLR, and PLR; (E) scatter dot presentation comparison of AFR and Fib. *P < 0.05, **P < 0.01, ***P < 0.001.

Figure 5

Kaplan–Meier curves of stage II–III NSCLC patients with treatment of chemo‐radiotherapy(C therapy) or combined surgical resection and chemo‐radiology (SC therapy) in low and high AFR subgroups and predicted nomogram including or without AFR for NSCLC patients. (A) Kaplan–Meier curve for overall survival probability within stage II–III NSCLC patients receiving chemo‐radiotherapy according to circulating AFR concentration; (B and C): Kaplan–Meier curve for overall survival probability within stage II–III NSCLC patients according to two therapy methods in low AFR group and high‐AFR group, respectively; (D) nomogram including AFR for predicting 3‐year OS in NSCLC patients undergoing chemo‐radiotherapy. (E) nomogram without AFR for predicting 3‐year OS in NSCLC patients undergoing chemo‐radiotherapy.