Neutrophil-to-Apolipoprotein A1 Ratio Predicted Overall Survival in Hepatocellular Carcinoma Receiving Transarterial Chemoembolization

Abstract

Purpose. To investigate the predictive capability of Neutrophil-to-Apolipoprotein A1 ratio (NAR) for predicting overall survival (OS) among hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE). Patients and methods. We investigated the clinical features of 554 HCC patients receiving TACE and assessed NAR's predictive value for OS with 222 consisting the discovery cohort and 332 consisting the validation cohort. The association of NAR with circulation LOX-1 + polymorphonuclear myeloidderived suppressor cells (PMN-MDSC) were illustrated. Results. Multivariate Cox regression revealed lymphocyte count, TNM stage and NAR were independent prognostic factors in discovery cohort. Validation cohort confirmed the independent prognostic value of TNM stage and NAR. Patients with low NAR (<2.7) displayed significantly increased OS in the discovery cohort (59.8 months vs 21 months), validation group (38.0 months vs 23.6 months) and the total cohort (44.1 months vs 22.0 months). Then Cox proportional hazards model was conducted to combine Cancer of the Liver Italian Program (CLIP) score with discretized NAR. C-index illustrated that NAR integrated CLIP score was best model compared with NAR and CLIP score. Furthermore, NAR-CLIP presented superior predictive capacity for 10, 20, 30, 40, 50 and 60-month survival compared with CLIP by survival ROC analysis in the discovery cohort, validation cohort and total cohort. NAR was significantly associated with LOX-1 + PMN-MDSC by linear regression. Conclusion. In summary, the present study identified NAR as an independent predictor for OS among HCC patients receiving TACE. NAR reflected circulation LOX-1 + PMN-MDSC level. The Oncologist 2021;9999:• • Implications for Practice: The present study identified Neutrophil-to-Apolipoprotein A1 Ratio (NAR) as an independent predictor for overall survival among hepatocellular carcinoma patients receiving Transarterial Chemoembolization. NAR reflected circulation LOX-1+ PMN-MDSC level.

Association of the MACROD2 rs6110695 A>G polymorphism with an increasing WBC count in a Korean population

“…Although the underlying mechanism of lipid profile alterations with the MACROD2 rs6110695 A>G polymorphism cannot be elucidated by our findings, a previous study reported that a high WBC to apolipoprotein A‐I ratio is significantly related to long‐term adverse prognosis in CVD 31 . Similarly, the neutrophil to apolipoprotein A‐I ratio was identified as a novel predictor for overall survival in patients with hepatocellular carcinoma 32 . Maintenance of a high WBC to apolipoprotein A‐I ratio seems to be related to poor prognosis of diseases; hence, having the rs6110695 AG genotype is somewhat unfavorable.…”

“… 31 Similarly, the neutrophil to apolipoprotein A‐I ratio was identified as a novel predictor for overall survival in patients with hepatocellular carcinoma. 32 Maintenance of a high WBC to apolipoprotein A‐I ratio seems to be related to poor prognosis of diseases; hence, having the rs6110695 AG genotype is somewhat unfavorable.…”

Lipid metabolism and tumor immunotherapy

“…Moreover, relevant studies have shown that combining apoA-I and neutrophils may be a practical prognostic index for HCC patients undergoing transcatheter arterial chemoembolization. By studying the prognostic value and potential immune mechanism of the neutrophil apolipoprotein A ratio (NAR) in HCC patients receiving transcatheter arterial chemoembolization in two independent cohorts, researchers found that NAR showed prognostic performance similar to that obtained with the Cancer of the Liver Italian Program score, and when the score was adjusted by considering the NAR, the prediction for overall survival and survival rate at a specific time point was more accurate ( Chen et al, 2021 ). The generation of PMNs requires long-range intercellular communication continuously mediated by soluble or membrane-binding factors on primary tumours ( Liu and Cao, 2016 ; Peinado et al, 2017 ), and intercellular communication synapsis formation and timing are controlled by cholesterol.…”

“…Polymorphonuclear myeloid-derived suppressor cells are pathologically activated neutrophils that are essential for regulating the immune response to cancer. Lipid metabolism is a crucial regulator of PMN-MDSCs ( Veglia et al, 2019 ; Chen et al, 2021 ). A study found that fatty acid transporter 2 (FATP2) controlled the inhibitory activity of PMN-MDSCs.…”

Predictive value of neutrophil-to-apolipoprotein A1 ratio in all-cause and cardiovascular death in elderly non-valvular atrial fibrillation patients

“…NAR has a predictive value for long-term tumour disease prognosis [ 15 , 35 ]. However, data on NAR’s impact on the long-term prognosis of AF patients are limited.…”