As demonstrated by recent studies, inflammation and nutritional status play key roles in tumor progression [19]. It is also well known that nutritional status and chronic inflammation are two main causes for NSCLC [20]. This current study focused on the potential predictive factors for prognosis in early NSCLC patients who underwent surgical resection. Our results showed that the preoperative AFR was an independent risk factor for both RFS and OS in early NSCLC patients. Patients with a lower preoperative AFR had a worse RFS and OS than patients with a high preoperative AFR. In addition to the AFR, the present study also indicated that blood vessel invasion is a significant prognostic factor for PFS.
The prognostic role of FAR has been reported for patients with malignancies in recent studies, including esophageal squamous cell carcinoma, breast cancer, colorectal cancer and hepatocellular carcinoma [21–24]. Recently, AFR was reported to be a prognostic factor for clinical outcomes in lung cancer [25–27]. Chen et al. investigated 529 patients with stage I-III resectable NSCLC and identified AFR as an independent prognostic factor in multivariate analysis [17]. By evaluating 270 patients with stage IV NSCLC patients, Ying et al. found that patients with an initial AFR greater 8.02 had a better survival than those with an initial AFR less than or equal to 8.02 [18]. Recently, Li et al. have demonstrated that AFR is a potentially useful marker for predicting the response and prognosis of stage II-III patients NSCLC undergoing chemo-radiotherapy [19]. However, the prognostic value of preoperative AFR patients with stage I NSCLC has not been investigated. Stage I NSCLC account for 15%-20% of newly diagnosed NSCLC, and this subgroup has high survival rate after surgery. A small percentage of patients with stage I NSCLC patients died from recurrence or metastasis within the short period of time. Better prognostic stratification will identify high-risk patients and allow the design of prospective adjuvant therapy. Unlike previous studies, we conducted a retrospective study to investigate the prognostic value of pre-operative AFR in a uniform patient cohort and found a strong association between increased AFR and better survival, including RFS and OS, according to the Cox model, it was also an independent prognostic factor for survival in multivariate analysis. Our results are consistent with previous reports [25–27].
Moreover, Fib and Alb are widely accepted as two acute phase response proteins for the systemic inflammatory status [28]. Fib and Alb are both synthesized by hepatocytes and they vary oppositely under inflammatory stimulation [29]. In short, FAR is a key factor in nutrition condition, coagulation system, and systemic inflammation. Furthermore, these processes were closely associated with the survival, intravasation, and adhesion of tumor cells, leading to increased metastatic potential, which might be a possible explanation for the prognostic role of FAR in NSCLC patients [30].
The cut-off value of AFR in NSCLC is different, varying from 7.80 to 9.67 [25–27]. By using ROC, the cut-off value of AFR was 10.36 in our study, which is comparable with previous studies. The relationship between AFR and clinical parameters was explored. In our study, significant associations between AFR and stage, lymph vessel invasion and blood vessel invasion were identified. Compared with the high AFR group, the rate of recurrence was higher in the low AFR group. To the best of our knowledge, this study may represent the first report of an association between AFR and recurrence rate.
Several limitations of the study should be considered. The main limitation of this study is that, as it is a retrospective study, we can't completely rule out selection bias. Second, although the preoperative Alb and Fib levels were obtained in routine clinical practice and analyzed in our hospital's regular laboratory, we did not perform a specific quality control analysis. Finally, the determination of Alb and Fib levels may be influenced by different factors, although we tried to limit the influence of other factors.