Background: Smoldering cancer-related inflammation attenuates chemotherapy efficacy and contributes to unsatisfactory outcome for patients of colorectal cancer (CRC). Various inflammation-based biomarkers were reported to predict the survival of the disease, however, it remains unclear which is the best inflammation-based biomarker. The aim of present study was to compare the prognostic role of those biomarkers and to establish superior survival score for post-recurrence survival in radically operative patients with stage II–III CRC.
Patients and Methods: Preoperative peripheral neutrophil, lymphocyte, monocyte, platelet, serum albumin (Alb), pre-Alb, and plasma fibrinogen (Fib) were detected in the discovery and validation cohort which included a total of 1533 stage II–III surgical CRC patients. We calculated and compared fourteen inflammation-based biomarkers for predicting recurrence-free survival (RFS) of the patients with stage II–III CRC.
Results: In this study, the platelet to lymphocyte ratio (PLR), lymphocyte to monocyte (LMR), systemic inflammation response index (SIRI), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), modified systemic inflammation score (mSIS), fibrinogen and neutrophil to lymphocyte ratio score (F-NLR), ratio of Alb to Fib (AFR), and ratio of Fib to pre-Alb (FPR) were all related to the RFS of the patients in both discovery and validation cohorts, however, only the LMR, SIRI, PNI, mSIS, F-NLR, AFR and FPR remained independent predictors for RFS in multivariate analysis. Both the C-index of the FPR (0.629 for 36 months) and the areas under the time-dependent receiver operating characteristic (ROC) curves (0.625 for 12 months, 0.641 for both 24 and 0.637 months) showed that it was superior to the other inflammation-based prognostic scores for predicting the RFS of stage II–III surgical CRC patients. Moreover, elevated FPR was significantly associated with unsatisfactory RFS regardless of TNM stage and primary tumor location. Stage II low FPR patients showed the best RFS regardless of chemotherapy. The better RFS was observed in chemotherapy-treated stage II high FPR patients than those without the treatment, and the outcomes of patients with treatment of XELOX, capecitabine and XELOX were superior to the other regimens to treat patients in stage III low- and high-FPR populations, respectively. Additionally, the carcinoembryonic antigen (CEA)-FPR combined score one (adjusted HR=2.764, 95% CI=2.129– 3.589) and two (adjusted HR=3.543, 95% CI=2.317– 5.420) were extremely associated with RFS of these patients, and the predicted AUC of the combined score for 12, 24 and 36 months were 0.657, 0.657 and 0.653 in stage II–III patients, which were superior to the single CEA and FPR, respectively.
Conclusion: In conclusion, FPR is superior to the other inflammatory biomarkers as a useful recurrence indicator in stage II–III surgical CRC patients in terms of prognostic ability; it helps to choose the effective chemotherapy regimen and to increase the predicted efficacy of CEA and the combined CEA and FPR score could effectively predict recurrence of the patients.



中文翻译：

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癌症诱发的炎症生物标志物在预测 II-III 期结直肠癌患者可治愈切除术后早期复发中的作用

背景：冒烟的癌症相关炎症会减弱化疗效果，并导致结直肠癌 (CRC) 患者的结果不令人满意。据报道，各种基于炎症的生物标志物可以预测疾病的存活率，但是，目前尚不清楚哪种基于炎症的生物标志物最好。本研究的目的是比较这些生物标志物的预后作用，并为 II-III 期 CRC 根治性手术患者的复发后生存建立优越的生存评分。
患者和方法：在发现和验证队列中检测到术前外周中性粒细胞、淋巴细胞、单核细胞、血小板、血清白蛋白 (Alb)、前白蛋白和血浆纤维蛋白原 (Fib)，其中包括 1533 名 II-III 期手术 CRC 患者。我们计算并比较了 14 种基于炎症的生物标志物，用于预测 II-III 期 CRC 患者的无复发生存期 (RFS)。
结果：在本研究中，血小板与淋巴细胞比率（PLR）、淋巴细胞与单核细胞（LMR）、全身炎症反应指数（SIRI）、预后营养指数（PNI）、全身免疫炎症指数（SII）、改良全身炎症评分（mSIS） )、纤维蛋白原和中性粒细胞与淋巴细胞的比率评分 (F-NLR)、Alb 与 Fib 的比率 (AFR) 以及 Fib 与前 Alb 的比率 (FPR) 均与发现和验证队列中患者的 RFS 相关然而，在多变量分析中，只有 LMR、SIRI、PNI、mSIS、F-NLR、AFR 和 FPR 仍然是 RFS 的独立预测因子。FPR 的 C 指数（36 个月为 0.629）和时间相关接受者操作特征 (ROC) 曲线下面积（12 个月为 0.625，24 个月和 0 个月均为 0.641。637 个月）表明，它在预测 II-III 期手术 CRC 患者的 RFS 方面优于其他基于炎症的预后评分。此外，无论 TNM 分期和原发肿瘤位置如何，升高的 FPR 都与不满意的 RFS 显着相关。无论化疗如何，II 期低 FPR 患者均表现出最佳 RFS。在接受化疗的 II 期高 FPR 患者中观察到比未接受治疗的患者更好的 RFS，并且接受 XELOX、卡培他滨和 XELOX 治疗的患者的结局优于其他方案治疗 III 期低和高 FPR 患者的患者FPR 人群，分别。此外，癌胚抗原 (CEA)-FPR 综合得分为 1（调整后的 HR=2.764，95% CI=2.129-3.589）和 2 分（调整后的 HR=3.543，95% CI=2.317-5。
结论：总之，就预后能力而言，FPR 在 II-III 期手术 CRC 患者中作为有用的复发指标优于其他炎症生物标志物；有助于选择有效的化疗方案，提高CEA的预测疗效，联合CEA和FPR评分可以有效预测患者的复发。