Quantification of Fibrinogen-to-Pre-Albumin Ratio Provides an Integrating Parameter for Differential Diagnosis and Risk Stratification of Early-Stage Colorectal Cancer
Authors: Ying Hou-Qun , Chen Wei , Xiong Cui-Fen , Wang Yuanyuan , Li Xiao-Juan , Cheng Xue-Xin 
Published: October 2021

Abstract
Background: Circulating fibrinogen to pre-albumin ratio (FPR) and albumin to fibrinogen ratio (AFR) are effective factors for predicting the prognosis of colorectal cancer (CRC). However, the role of these two ratios in diagnosing early-stage CRC and identifying the stage II CRC subgroup with high relapse risk remains unknown. This study aimed to assess the potential of FPR and AFR in differential diagnosis and risk stratification of early-stage CRC.Methods: Two-stage cohorts (discovery and validation) including 895 patients with colorectal benign polyps patients and 714 patients with stage I-II CRC were enrolled in this study. Receiver operating characteristic curve (ROC), Kaplan-Meier curve, and time-dependent ROC were used to evaluate the diagnostic efficacy of AFR and FPR in the two cohorts and overall population, and the discriminating role of FPR in identifying clinical high-relapse risk patients in comparison with common clinical characteristics in stage II CRC patients.Results: The area under the curve (AUC) of the preoperative circulating FPR was higher than that of AFR in the diagnosis of stage I-II CRC from colorectal adenomas, and colorectal benign polyps in the discovery and validation cohorts and overall population. Preoperative FPR combined with carcinoembryonic antigen (CEA) could effectively discriminate early-stage CRC from colorectal adenomas or benign polyps in the discovery and validation cohorts and overall population. Preoperative FPR could effectively distinguish stage II subgroups with high and low relapse risk, and was found to be superior to common clinical characteristics in identifying high-risk patients who could benefit from adjuvant chemotherapy (CT) post-surgery [time-dependent AUC: 0.637 vs. 0.511, p<0.001 for predicting recurrence-free survival (RFS); 0.719 vs. 0.501, p<0.001 for predicting overall survival (OS)]. Furthermore, patients with FPR>20 and stage II CRC treated with CT had the highest recurrence (31.16%) and death rates (21.88%), with similar highest recurrence (30.70%) and death (26.92%) rates found in non-CT-treated patients with FPR>20. Stage II CRC patients with 20≥FPR>15 could significantly benefit from postoperative CT, as the recurrence (33.30%) and death (35.71%) rates within non-CT treated patients were approximately five times higher than those of the CT-treated cases (6.77% and 7.41% for the recurrence and death rates, respectively). No significant difference in recurrence rate was observed between L-FPR (≤15) patients with (10.00%) or without CT (9.76%), indicating that these patients might not require to receive adjuvant CT after curative resection.Conclusions: Preoperative FPR combined with CEA is superior to common tumor biomarker or either FPR, or AFR in distinguishing early-stage CRC from colorectal benign polys. Circulating FPR can be considered as an effective biomarker to identify high-risk patients and to choose suitable therapeutics for early-stage CRC.