Retrospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2015; 21(38): 10898-10906
Published online Oct 14, 2015. doi: 10.3748/wjg.v21.i38.10898
Lymphocyte-to-monocyte ratio predicts survival of patients with hepatocellular carcinoma after curative resection
Ze-Xiao Lin, Dan-Yun Ruan, Yang Li, Dong-Hao Wu, Xiao-Kun Ma, Jie Chen, Zhan-Hong Chen, Xing Li, Tian-Tian Wang, Qu Lin, Jing-Yun Wen, Xiang-Yuan Wu
Ze-Xiao Lin, Dan-Yun Ruan, Dong-Hao Wu, Xiao-Kun Ma, Jie Chen, Zhan-Hong Chen, Xing Li, Tian-Tian Wang, Qu Lin, Jing-Yun Wen, Xiang-Yuan Wu, Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Yang Li, Department of Liver Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Author contributions: Lin ZX, Ruan DY and Li Y contributed to this work equally and should be regarded as co-first authors; Lin ZX, Ruan DY and Li Y conceived and designed the study; Wu DH, Ma XK, Chen J, Chen ZH, Li X, Wang TT, Lin Q and Wen JY performed the study; Lin ZX, Ruan DY and Li Y analyzed the data; Lin ZX drafted and revised the manuscript; all authors have read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81372374; the Combination Project of Production, Education and Research from Guangdong Province and Ministry of Education, No. 2012B091100460; and the Natural Science Foundation of Guangdong, No. 2014A030313146.
Institutional review board statement: This study protocol was approved by the Clinical Ethics Review Board of The Third Affiliated Hospital of Sun Yat-sen University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: None of the authors declared a potential conflict of interest related to this manuscript. None of the authors have received a fee for serving as a speaker for any organization, and none have received research funding from any organization. The authors are not employees of any organization and do not own stocks and/or shares in any organization. The authors do not own patents.
Data sharing statement: Technical appendix, statistical code, and dataset are available from the corresponding author at wuxiangy@mail.sysu.edu.cn. Participants provided informed consent for data sharing. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xiang-Yuan Wu, MD, Professor, Chief, Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou 510630, Guangdong Province, China. wuxiangy@mail.sysu.edu.cn
Telephone: +86-20-85252217 Fax: +86-20-85252092
Received: March 5, 2015
Peer-review started: March 6, 2015
First decision: April 24, 2015
Revised: May 11, 2015
Accepted: August 31, 2015
Article in press: August 31, 2015
Published online: October 14, 2015
Abstract

AIM: To investigate the prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR) in patients with hepatocellular carcinoma (HCC) undergoing curative hepatectomy.

METHODS: Clinicopathological data of 210 hepatitis B virus (HBV)-associated HCC patients who were treated by radical hepatic resection between 2003 and 2010 were retrospectively analyzed. None of the patients received any preoperative anticancer therapy or intraoperative radiofrequency ablation. The diagnosis was confirmed by pathological examination after surgery. Absolute peripheral blood lymphocyte and monocyte counts were derived from serum complete blood cell count before surgery, and LMR was calculated by dividing lymphocyte count by monocyte count. The best cutoff was determined by receiver operating characteristics (ROC) curve analysis. Correlations between LMR levels and clinicopathological features were assessed using the χ2 test. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Univariate and multivariate analyses were performed to evaluate the prognostic impact of LMR and other clinicopathological factors on overall survival (OS) and recurrence-free survival (RFS), using the Cox proportional hazards model.

RESULTS: The optimal cutoff value of LMR for survival analysis was 3.23, which resulted in the most appropriate sensitivity of 55.3% and specificity of 74.7%, with the area under the curve (AUC) of 0.66 (95%CI: 0.593-0.725). All patients were dichotomized into either a low (≤ 3.23) LMR group (n = 66) or a high (> 3.23) LMR group (n = 144). A low preoperative LMR level was significantly correlated with the presence of cirrhosis, elevated levels of total bilirubin and larger tumor size. Patients with a low LMR level had significantly reduced 5-year OS (61.9% vs 83.2%, P < 0.001) and RFS (27.8% vs 47.6%, P = 0.009) compared to those with a high LMR level. Multivariate analyses indicated that a lower LMR level was a significantly independent predictor of inferior OS (P = 0.003) and RFS (P = 0.006). Subgroup analysis indicated that survival outcome was significantly more favorable in cirrhotic patients with LMR > 3.23. However, there were no differences between low and high LMR groups for OS and RFS in non-cirrhotic patients.

CONCLUSION: Preoperative LMR was demonstrated for the first time to serve as an independent prognostic factor in HBV-associated HCC patients after curative resection. Prospective studies with larger cohorts for validation are warranted.

Keywords: Hepatocellular carcinoma, Liver resection, Lymphocyte-to-monocyte ratio, Prognosis, Prognostic factor

Core tip: Inflammatory microenvironment plays an important role in the progression of hepatocellular carcinoma (HCC). Peripheral blood lymphocyte-to-monocyte ratio (LMR), a novel inflammatory biomarker that combines estimates of host immune homeostasis and tumor microenvironment, has been found to serve as a predictor of clinical outcomes in various malignancies. Prior to this study, there have been no reports regarding the prognostic value of LMR in HCC patients. For the first time in literature, our study identified the optimal cutoff value of LMR for survival analysis and concluded that preoperative LMR could serve as an independent prognostic factor in hepatitis B virus-associated HCC patients after curative resection.