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Objective Cancer elicited inflammation is the main environmental cause leading to carcinogenesis and metastasis of non-small cell lung cancer (NSCLC). Roles of the inflammatory biomarker in predicting the clinical efficacy of tyrosine kinase inhibitor (TKI) and prognosis of naive patients with advanced NSCLC need to be determined, and the best inflammatory predicted biomarker remains unknown. Methods A total of 178 eligible advanced NSCLC patients (124 and 54 cases within discovery and validation cohorts, respectively) who received first-line EGFR-TKI between July of 2014 and October of 2020 were enrolled in the present study. We detected circulating immune cell counting, albumin (Alb), pre-albumin (pAlb), ALP, AST, LDH, GGT, HDL-c, and fibrinogen (Fib) concentrations, and calculated 22 inflammatory ratios and scores. Logistic regression and Cox proportional hazards models were used to assess the impact of these ratios and scores on objective response and disease control rate (ORR and DCR) as well as progression-free survival (PFS) in these patients. Results Twenty-five percentage and 24.07% of NSCLC patients were observed objective response to the treatment of first-line EGFR-TKI in discovery and validation cohort, respectively. Univariate and multivariate Cox regression showed that high PLR, NPS, SII, SIS, mSIS, GLR and FPR as well as low PNI were significantly associated with poor PFS in discovery cohort. However, only high SII and FPR were found to be associated with unsatisfactory outcome in validation cohort. Time-dependent areas under ROC of FPR were 0.702 (0.517–0.888) in discovery cohort, and 0.767 (0.613–0.921) in validation cohort, which were extremely higher than the other biomarkers. The patients with FPR-SII combined score 2 harbored worse prognosis compared to the combined score 0 in discovery (plog-rank = 0.003, adjusted HR = 2.888, 95%CI = 1.500–5.560) and validation cohort (plog-rank = 0.001, adjusted HR = 3.769, 95%CI = 1.676–8.478) as well as overall population (plog-rank Conclusions High-grade cancer elicited inflammation could attenuates response and outcome in tyrosine kinase inhibitor naive patients with advanced NSCLC. FPR-SII combined score was the best inflammatory biomarker to monitor and predict the progression of advanced NSCLC patients with treatment of TKI.

Yu-Cui Liao,1,* Hou-Qun Ying,2,* Ying Huang,3,* Yan-Ran Luo,3 Cui-Fen Xiong,3 Ruo-Wei Nie,3 Xiao-Juan Li,4 Xue-Xin Cheng1 1School of Public Health; Jiangxi Provincial Key Laboratory of Preventive Medicine, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 2Department of Nuclear Medicine, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of China; 3Jiangxi Medical College, Nanchang University, Nanchang, 330006, People’s Republic of China; 4Department of Clinical Laboratory, Kunming Children’s Hospital, Kunming, Yunnan, 650500, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xue-Xin ChengSchool of Public Health; Jiangxi Provincial Key Laboratory of Preventive Medicine Nanchang University, No. 1 Of Minde Road, Nanchang, People’s Republic of ChinaTel/Fax +86 0791-86297662Email cxxncu@163.comBackground: Cancer-related inflammation is the main cause of the progression of mucinous colorectal adenocarcinoma (MCA). Circulating fibrinogen-to-pre-albumin ratio (FPR) is associated with the clinical outcome in colorectal cancer (CRC). However, the prognostic role of FPR and which is the best inflammatory prognostic biomarker within MCA remain unknown.Methods: We enrolled 157 patients with stage I–III MCA in this study. Kaplan-Meier curve, Cox regression, and time-dependent receiver operation characteristic curve analysis were performed to assess the prognostic value and efficacy of the neutrophil-to-albumin ratio (NAR), neutrophil-to-pre-albumin ratio (NPAR), albumin-to-alkaline phosphatase ratio (AAPR), albumin-to-globulin ratio (AGR), albumin-to-fibrinogen ratio (AFR), and FPR in these patients.Results:: We found that NAR, NPAR, and FPR were significantly associated with unsatisfactory recurrence-free survival (RFS) in patients with stage I–III MCA, and the predicted efficacy of FPR was superior to that of the other two inflammatory biomarkers. Moreover, patients with a high combined TNM-CA199-FPR score had worse outcomes, with a high predicted efficacy of up to 0.779 (0.703– 0.856). Using FPR, the patient was monitored for the recurrence up to two months earlier than that achieved using the common imaging techniques (4 vs 6 median months) in stage I–III MCA patients undergoing radical resection.Conclusion: FPR is the preferred inflammatory biomarker and commonly used for predicting and monitoring recurrence in stage I–III MCA patients. The combined TNM-CA199-FPR score is an economical, simple, effective, and independent prognostic factor for localized disease.Keywords: mucinous colorectal carcinoma, fibrinogen-to-pre-albumin ratio, prognosis, inflammation