Elevated FPR confers to radiochemoresistance and predicts clinical efficacy and outcome of metastatic colorectal cancer patients

Abstract

Association of chronic inflammation, primary tumor sidedness, adjuvant therapy and survival of metastatic colorectal cancer (mCRC) remains unclear. Circulating inflammatory cell, fibrinogen (Fib), albumin (Alb), pre-albumin (pAlb), Alb/Fib (AFR) and Fib/pAlb (FPR) were detected, and clinical outcome was obtained to determine the predictive, prognostic and monitoring roles of them in discovery and validation cohort. We found that elevated FPR, low AFR and poor survival was observed in right-sided mCRC comparing to the left-sided disease, elevated FPR harbored the highest areas under curve to independently predict poor progression-free survival and overall survival in overall and left-sided mCRC case in two cohorts. No survival difference was examined between the two-sided patients in subgroups stratified by FPR. Radiochemoresistance was observed in high FPR case. However, the patient could benefit from bevacizumab plus radiochemotherapy. Low FPR patient showed the best survival with treatment of palliative resection plus radiochemotherapy. Moreover, circulating FPR was significantly increased ahead imaging confirmed progression and it reached up to the highest value within three months before death. Additionally, c-indexes of the prognostic nomograms including FPR were significantly higher than those without it. These findings indicated that FPR was an effective and independent factor to predict progression, prognosis and to precisely identify the patient to receive optimal therapeutic regimen.

Chemotherapy plus bevacizumab as an optimal first-line therapeutic treatment for patients with right-sided metastatic colon cancer: a meta-analysis of first-line clinical trials

“…Right-sided mCRC might induce impaired sensitivity to common chemotherapy, leading to different benefits from first-line chemotherapy between the right-sided and left-sided cases. The finding was consistent with our previous study 31. A recent study by Loupakis and his coworkers reported that the right-sided and left-sided patients could significantly benefit from the treatment of chemotherapy plus bevacizumab, especially in the left-sided cases 13.…”

Circulating Fibrinogen to Pre-albumin Ratio for Chemotherapy Efficacy Prediction and Prognosis of Colorectal Cancer Patients

“…In our previous studies, we found an association between circulating high FPR and poor prognosis in stage II-III and IV CRC patients [20,28]. In the current study, univariate Cox regression revealed a signi cant association between high FPR and poor disease outcomes across each stage.…”

“…Previous studies have demonstrated that in ammatory cytokines produced from CRC microenvironment and kupfer cells, including interleukin-6, effectively suppress Alb and preAlb synthesis by hepatocytes [26]. Consequently, CRC patients, especially those at advanced stages, have been found to commonly manifest malnutrition or hypoalbuminemia [20,27]. In the present study, we found signi cantly higher circulating FPR in large cancer bulk and distal metastatic subgroups than those with small cancer bulk and non-distal metastatic patients, respectively, although this was gradually elevated according to increased cancer bulk.…”

“…Comparisons differences among categorical variables were done using the Chisquare or Fisher's exact tests, whereas those across continuous variables with skewed distribution were done using the Mann-Whitney U test. Optimal FPR cut-off points across three years OS, at each disease stage were determined using the X-tile 3.6.1 software (Yale University, New Haven, CT, USA) as described in our previous studies 20,28 . Differences in survival rates were calculated using Kaplan-Meier curves, with the log-rank test, whereas the prognostic role of clinical baseline characteristics and indicators detected in the laboratory were analyzed using the Cox proportional regression with hazard ratio (HR) at a 95% con dence interval (CI).…”

“…In fact, previous studies have demonstrated that ratios of Alb to Fib (AFR) and Fib to pAlb (FPR) are independent markers for predicting clinical outcomes in many kinds of solid malignancies, including non-small cell lung cancer [16], esophageal, hepatocellular and gastric cancers [17][18][19]. In our previous study, we demonstrated that preoperative FPR is closely associated with chemoresistance and outcomes of metastatic CRC [20]. However, the role of quantitative FPR in impairment or resistance to chemotherapy remains unclear.…”