Prognostic Impact of Monocyte to Lymphocyte Ratio in Clinical Outcome for Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

  • Masoud Nouri-Vaskeh 1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2. Network of Immunity in Infection, Malignancy and Autoimmunity, Universal Scientific Education and Research Network, Tehran, Iran
  • Mohammad Mirza-Aghazadeh-Attari 3. Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
  • Fariba Pashazadeh 4. Iranian EBM Centre: A Joanna Briggs Institute Affiliated Group 5. Research Center for Evidence-Based Medicine, Health Management and Safety Promotion Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
  • Saber Azami-Aghdash 6. Tabriz Health Services Management Research Center, Health Management and Safety Promotion Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
  • Hadi Alizadeh 7. Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  • Parnia Pouya 7. Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  • Monireh Halimi 8. Department of Pathology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
  • Golamreza Jadideslam 9. Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
  • Mohammad Zarei 10. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA 11. Center for Mitochondrial and Epigenomic Medicine, Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Keywords: Hepatocellular Carcinoma; Liver Neoplasm; Lymphocyte to Monocyte Ratio; Survival; Disease-Free Survival


Background: Lymphocyte to monocyte ratio (LMR) is a surrogate marker of systemic inflammation which is shown to be related to the patient’s survival in multiple malignancies. An important implication of this marker potentially is neoplasms in which there is no correlation between prognosis and histopathological staging and also has no reliable chemical markers associated with prognosis. Herein, this meta-analysis aimed to investigate the prognostic role of LMR in patients with hepatocellular carcinoma (HCC). Materials and Methods: In the current systemic review and meta-analysis, we conducted a systemic search of databases and indexing sources, including PubMed, EMBASE, Cochrane, Scopus, and ProQuest up to May 2019 toinclude studies on the prognostic significance of LMR on patients with HCC. Overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) values were extracted from the studies and analyzed. The pooled hazard ratio with a 95% confidence interval was explored to identify the prognostic value of the LMR in the survival of the patients with HCC. Results: A total of 12 studies with a total sample size of 3750 cases were included. There was significant heterogeneity among the studies; therefore, subgroup analysis was also performed. Overall analysis regarding OS showed an insignificant relationship between LMR and patient’s prognosis, dividing to subgroups based on LMR cut-offs did not yield any significant result, subgroup analysis for RFS founded statistically significant results and LMR was significantly related to DFS. Conclusion: High LMR was associated with increased DFS and RFS, in return this association was not observed for OS. [GMJ.2020;9:e1948]

Author Biography

Monireh Halimi, 8. Department of Pathology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Associate professor


Ghouri YA, Mian I, Rowe JH. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis. J Carcinog. 2017;16:1.

PMid:28694740 PMCid:PMC5490340

Yu LX, Ling Y, Wang HY. Role of nonresolving inflammation in hepatocellular carcinoma development and progression. NPJ Precis Oncol. 2018;2(1):6.

PMid:29872724 PMCid:PMC5871907

Volcic M, Karl S, Baumann B, Salles D, Daniel P, Fulda S, et al. NF-κB regulates DNA double-strand break repair in conjunction with BRCA1-CtIP complexes. Nucleic Acids Res. 2012;40(1):181-95.

PMid:21908405 PMCid:PMC3245919

Taniguchi K, Karin M. NF-kappaB, inflammation, immunity and cancer: coming of age. Nat Rev Immunol. 2018;18(5):309-24.


Adam JK, Odhav B, Bhoola KD. Immune responses in cancer. Pharmacol Ther. 2003;99(1):113-32.

Chen G, Zhu L, Yang Y, Long Y, Li X, Wang Y. Prognostic Role of Neutrophil to Lymphocyte Ratio in Ovarian Cancer: A Meta-Analysis. Technol Cancer Res Treat. 2018;17:1533033818791500.

PMid:30145940 PMCid:PMC6111397

Zhao J, Huang W, Wu Y, Luo Y, Wu B, Cheng J, et al. Prognostic role of pretreatment blood lymphocyte count in patients with solid tumors: a systematic review and meta-analysis. Cancer cell international. 2020;20:15-.

PMid:31938023 PMCid:PMC6954501

Liu L, Gong Y, Zhang Q, Cai P, Feng L. Prognostic Roles of Blood Inflammatory Markers in Hepatocellular Carcinoma Patients Taking Sorafenib. A Systematic Review and Meta-Analysis. Front Oncol. 2019;9:1557.

PMid:32064238 PMCid:PMC7000550

Mao Y, Chen D, Duan S, Zhao Y, Wu C, Zhu F, et al. Prognostic impact of pretreatment lymphocyte-to-monocyte ratio in advanced epithelial cancers: a meta-analysis. Cancer Cell Int. 2018;18:201.

PMid:30534002 PMCid:PMC6282251

Li J, Cheng Y, Ji Z. Prognostic value of pretreatment lymphocyte-to-monocyte ratio in patients with urologic tumors: A PRISMA-compliant meta-analysis. Medicine. 2019;98(2):e14091.

PMid:30633220 PMCid:PMC6336582

Wells G. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analysis. http://wwwohrica/programs/clinical_epidemiologyoxfordhtm. 2004.

Djordjevic D, Rondovic G, Surbatovic M, Stanojevic I, Udovicic I, Andjelic T, et al. Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome and Nature of Bacteremia? Mediators Inflamm. 2018;2018:3758068.

PMid:30116146 PMCid:PMC6079471

Badalamenti G, Fanale D, Incorvaia L, Barraco N, Listi A, Maragliano R, et al. Role of tumor-infiltrating lymphocytes in patients with solid tumors: Can a drop dig a stone? Cell Immunol. 2019;343.


Green AR, Aleskandarany MA, Ali R, Hodgson EG, Atabani S, De Souza K, et al. Clinical Impact of Tumor DNA Repair Expression and T-cell Infiltration in Breast Cancers. Cancer Immunol Res. 2017;5(4):292-9.


Riabov V, Gudima A, Wang N, Mickley A, Orekhov A, Kzhyshkowska J. Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Frontiers in physiology. 2014;5:75-.

PMid:24634660 PMCid:PMC3942647

Aras S, Zaidi MR. TAMeless traitors: macrophages in cancer progression and metastasis. Br J Cancer. 2017;117(11):1583-91.

PMid:29065107 PMCid:PMC5729447

Goto W, Kashiwagi S, Asano Y, Takada K, Takahashi K, Hatano T, et al. Predictive value of lymphocyte-to-monocyte ratio in the preoperative setting for progression of patients with breast cancer. BMC Cancer. 2018;18(1):1137.

PMid:30453914 PMCid:PMC6245848

Kano S, Homma A, Hatakeyama H, Mizumachi T, Sakashita T, Kakizaki T, et al. Pretreatment lymphocyte-to-monocyte ratio as an independent prognostic factor for head and neck cancer. Head Neck. 2017;39(2):247-53.


Song W, Tian C, Wang K, Zhang R-J, Zou S-B. The pretreatment lymphocyte to monocyte ratio predicts clinical outcome for patients with hepatocellular carcinoma: A meta-analysis. Scientific reports. 2017;7:46601-.

PMid:28417972 PMCid:PMC5394547

Gong J, Jiang H, Shu C, Hu M-Q, Huang Y, Liu Q, et al. Prognostic value of lymphocyte-to-monocyte ratio in ovarian cancer: a meta-analysis. Journal of ovarian research. 2019;12(1):51-.

PMid:31151469 PMCid:PMC6544921

Zhang J, Chen L, Zhou R, Sun H, Liao Y, Liao W. Pretreatment lymphocyte monocyte ratio predicts long-term outcomes in patients with digestive system tumor: a meta-analysis. Gastroenterol Res Pract. 2016;2016:9801063.

PMid:27594882 PMCid:PMC4993921

Zhang Y, Shi S-M, Yang H, Yang L-X, Wang Z, Li X-D, et al. Systemic inflammation score predicts survival in patients with intrahepatic cholangiocarcinoma undergoing curative resection. J Cancer. 2019;10(2):494-503.

PMid:30719145 PMCid:PMC6360305

Liu L, Zhao Y, Jia J, Chen H, Bai W, Yang M, et al. The prognostic value of alpha-fetoprotein response for advanced-stage hepatocellular carcinoma treated with sorafenib combined with transarterial chemoembolization. Sci Rep. 2016;6:19851.

PMid:26831408 PMCid:PMC4735679

Fatourou EM, Suddle AR, Heneghan MA. Alpha-fetoprotein as a predictor of hepatocellular carcinoma recurrence following liver transplantation. Hepatoma Res. 2018;4:63.

Carr BI, Pancoska P, Branch RA. Low alpha-fetoprotein hepatocellular carcinoma. J Gastroenterol Hepatol. 2010;25(9):1543-9.


Peng D, Lu J, Hu H, Li B, Ye X, Cheng N. Lymphocyte to Monocyte Ratio Predicts Resectability and Early Recurrence of Bismuth-Corlette Type IV Hilar Cholangiocarcinoma. J Gastroint Surg. 2019:1-11.

PMid:30671792 PMCid:PMC7026310

Zhao Y-J, Ju Q, Li G-C. Tumor markers for hepatocellular carcinoma. Mol Clin Oncol. 2013;1(4):593-8.

PMid:24649215 PMCid:PMC3915636

Passacquale G, Vamadevan P, Pereira L, Hamid C, Corrigall V, Ferro A. Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes. PloS one. 2011;6(10):e25595.

PMid:22022418 PMCid:PMC3192052

Lisman T. Platelet-neutrophil interactions as drivers of inflammatory and thrombotic disease. Cell Tissue Res. 2018;371(3):567-76.

PMid:29178039 PMCid:PMC5820397

Lin Z-X, Ruan D-Y, Li Y, Wu D-H, Ma X-K, Chen J, et al. Lymphocyte-to-monocyte ratio predicts survival of patients with hepatocellular carcinoma after curative resection. World J Gastroenterol. 2015;21(38):10898.

PMid:26478681 PMCid:PMC4600591

Wu SJ, Lin YX, Ye H, Li FY, Xiong XZ, Cheng NS. Lymphocyte to monocyte ratio and prognostic nutritional index predict survival outcomes of hepatitis B virus-associated hepatocellular carcinoma patients after curative hepatectomy. J Surg Oncol. 2016;114(2):202-10.


Li G-J, Ji J-J, Yang F, Xu H-W, Bai Y. Preoperative lymphocyte-to-monocyte ratio predicts survival in primary hepatitis B virus-positive hepatocellular carcinoma after curative resection. Onco Targets Ther. 2017;10:1181.

PMid:28260933 PMCid:PMC5328305

Hong YF, Chen ZH, Wei L, Ma XK, Li X, Wen JY, et al. Identification of the prognostic value of lymphocyte-to-monocyte ratio in patients with HBV-associated advanced hepatocellular carcinoma. Oncol Lett. 2017;14(2):2089-96.

PMid:28789436 PMCid:PMC5530031

Shi S, Chen Q, Ye L, Yin D, Li X, Dai Z, et al. Prognostic value of systemic inflammation score in patients with hepatocellular carcinoma after hepatectomy. Oncotarget. 2017;8(45):79366.

PMid:29108315 PMCid:PMC5668048

Chen Z-H, Hong Y, Ma X-k, Li X, Wu D-h, Lin Q, et al. Identification of prognostic value of lymphocyte-to-monocyte ratio in patients with advanced HBV-associated hepatocellular carcinoma. Oncol Lett. 2016.

Yang T, Zhu J, Zhao L, Mai K, Ye J, Huang S, et al. Lymphocyte to monocyte ratio and neutrophil to lymphocyte ratio are superior inflammation-based predictors of recurrence in patients with hepatocellular carcinoma after hepatic resection. J Surg Oncol. 2017;115(6):718-28.


Conroy G, Salleron J, Belle A, Bensenane M, Nani A, Ayav A, et al. The prognostic value of inflammation-based scores in advanced hepatocellular carcinoma patients prior to treatment with sorafenib. Oncotarget. 2017;8(56):95853.

PMid:29221172 PMCid:PMC5707066

Yang Y-T, Jiang J-H, Yang H-J, Wu Z-j, Xiao Z-M, Xiang B-D. The lymphocyte-to-monocyte ratio is a superior predictor of overall survival compared to established biomarkers in HCC patients undergoing liver resection. Sci Rep. 2018;8(1):2535.

PMid:29416061 PMCid:PMC5803218

Takagi Y, Shimizu T, Ishizuka M, Shiraki T, Mori S, Iso Y, et al. Preoperative lymphocyte-to-monocyte ratio is useful for stratifying the prognosis of HCC patients with low CLIP scores. HPB. 2018;20:S371-S2.

Zhang L, Chen QG, Li SQ, Zhang J, Min QH, Gao QF, et al. Preoperative fibrinogen to prealbumin ratio as a novel predictor for clinical outcome of hepatocellular carcinoma. Future Oncol. 2019;15(1):13-22.


Shimizu T, Ishizuka M, Park KH, Shiraki T, Sakuraoka Y, Mori S, et al. Preoperative lymphocyte-to-monocyte ratio is useful for stratifying the prognosis of hepatocellular carcinoma patients with a low Cancer of the Liver Italian Program score undergoing curative resection. Ann Gastroenterol Surg. 2019;3(3):325-35.

PMid:31131362 PMCid:PMC6524078

Gilmore E, McCabe N, Kennedy RD, Parkes EE. DNA Repair Deficiency in Breast Cancer: Opportunities for Immunotherapy. J Oncol. 2019;2019:4325105.

PMid:31320901 PMCid:PMC6607732

Ni L, Lu J. Interferon gamma in cancer immunotherapy. Cancer medicine. 2018;7(9):4509-16.

PMid:30039553 PMCid:PMC6143921

Shen M, Wang J, Ren X. New Insights into Tumor-Infiltrating B Lymphocytes in Breast Cancer: Clinical Impacts and Regulatory Mechanisms. Front Immunol. 2018;9:470.

PMid:29568299 PMCid:PMC5852074

Han Y, Guo W, Ren T, Huang Y, Wang S, Liu K, et al. Tumor-associated macrophages promote lung metastasis and induce epithelial-mesenchymal transition in osteosarcoma by activating the COX-2/STAT3 axis. Cancer Lett. 2019;440-441:116-25.


Kondo M, Yamato M, Takagi R, Namiki H, Okano T. The regulation of epithelial cell proliferation and growth by IL-1 receptor antagonist. Biomaterials. 2013;34(1):121-9.


Mancino A, Lawrence T. Nuclear factor-kappaB and tumor-associated macrophages. Clin Cancer Res. 2010;16(3):784-9.

PMid:20103670 PMCid:PMC6485421

Hutchins AP, Diez D, Miranda-Saavedra D. The IL-10/STAT3-mediated anti-inflammatory response: recent developments and future challenges. Brief Funct Genomics. 2013;12(6):489-98.

PMid:23943603 PMCid:PMC3838198

Wan S, Zhao E, Kryczek I, Vatan L, Sadovskaya A, Ludema G, et al. Tumor-associated macrophages produce interleukin 6 and signal via STAT3 to promote expansion of human hepatocellular carcinoma stem cells. Gastroenterology. 2014;147(6):1393-404.

PMid:25181692 PMCid:PMC4253315

How to Cite
Nouri-Vaskeh, M., Mirza-Aghazadeh-Attari, M., Pashazadeh, F., Azami-Aghdash, S., Alizadeh, H., Pouya, P., Halimi, M., Jadideslam, G., & Zarei, M. (2020). Prognostic Impact of Monocyte to Lymphocyte Ratio in Clinical Outcome for Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Galen Medical Journal, 9, e1948.
Review Article