Application progress of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in various treatment methods of hepatocellular carcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

WANG Xin , WANG Junwei ,  WU Dequan

Department of General Surgery, The Second Clinical Hospital Affiliated to Harbin Medical University, Harbin 150086, P. R. China;

Corresponding?author：

WU Dequan, Email: dqwu56@163.com

Keywords：

hepatocellular carcinoma; neutrophil to lymphocyte ratio; platelet to lymphocyte ratio

DOI：

10.7507/1007-9424.202105056

Video：

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Objective To investigate the application progress of peripheral blood neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) in various treatment methods of hepatocellular carcinoma(HCC), aiming to fully understand the value of NLR and PLR in various treatments of HCC.Method Retrieved and reviewed domestic and foreign literatures related to peripheral blood NLR and PLR and HCC in recent years.Results The treatment of HCC mainly included liver resection, liver transplantation, transarterial chemoembolization, radiofrequency ablation, and sorafenib. Peripheral blood NLR and PLR were related to the survival of HCC patients after treatment. High NLR and PLR often indicated poor prognosis for HCC patients.Conclusion NLR and PLR play a certain role in various treatment methods of HCC, and have a certain value in judging tumor prognosis, recurrence, and metastasis.

Citation： WANG Xin, WANG Junwei, WU Dequan. Application progress of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in various treatment methods of hepatocellular carcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(4): 551-555. doi: 10.7507/1007-9424.202105056 Copy

1.	中華人民共和國國家衛生健康委員會醫政醫管局. 原發性肝癌診療規范 (2019年版). 中華消化外科雜志, 2020, 19(1): 1-20.
2.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
3.	Yang N, Han X, Yu J, et al. Hemoglobin, albumin, lymphocyte, and platelet score and neutrophil-to-lymphocyte ratio are novel significant prognostic factors for patients with small-cell lung cancer undergoing chemotherapy. J Cancer Res Ther, 2020, 16(5): 1134-1139.
4.	Jonska-Gmyrek J, Gmyrek L, Zolciak-Siwinska A, et al. Pretreatment neutrophil to lymphocyte and platelet to lymphocyte ratios as predictive factors for the survival of cervical adenocarcinoma patients. Cancer Manag Res, 2018, 10: 6029-6038.
5.	Yamazaki H, Sugino K, Matsuzu K, et al. Inflammatory biomarkers and dynamics of neutrophil-to-lymphocyte ratio in anaplastic thyroid carcinoma. Endocrine, 2020, 70(1): 115-122.
6.	Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet, 2001, 357(9255): 539-545.
7.	Saha S, Biswas SK. Tumor-associated neutrophils show phenotypic and functional divergence in human lung cancer. Cancer Cell, 2016, 30(1): 11-13.
8.	Rawat K, Syeda S, Shrivastava A. Neutrophil-derived granule cargoes: paving the way for tumor growth and progression. Cancer Metastasis Rev, 2021, 40(1): 221-244.
9.	Schmidt H, Bastholt L, Geertsen P, et al. Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model. Br J Cancer, 2005, 93(3): 273-278.
10.	陳媛媛, 蔡晶, 江楚怡. 腫瘤浸潤淋巴細胞的過繼性T細胞療法在宮頸癌中的研究進展. 河南醫學研究, 2021, 30(1): 189-192.
11.	Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science, 1986, 233(4770): 1318-1321.
12.	Paijens ST, Vledder A, de Bruyn M, et al. Tumor-infiltrating lymphocytes in the immunotherapy era. Cell Mol Immunol, 2021, 18(4): 842-859.
13.	Sanchez K, Kim I, Chun B, et al. Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer. Breast Cancer Res, 2021, 23(1): 2. doi: 10.1186/s13058-020-01378-4.
14.	Klein S, Mauch C, Brinker K, et al. Tumor infiltrating lymphocyte clusters are associated with response to immune checkpoint inhibition in BRAF V600 E/K mutated malignant melanomas. Sci Rep, 2021, 11(1): 1834. doi: 10.1038/s41598-021-81330-4.
15.	Yao J, Xi W, Chen X, et al. Mast cell density in metastatic renal cell carcinoma: Association with prognosis and tumour-infiltrating lymphocytes. Scand J Immunol, 2021, 93(4): e13006. doi: 10.1111/sji.13006.
16.	Morimoto Y, Nouso K, Wada N, et al. Involvement of platelets in extrahepatic metastasis of hepatocellular carcinoma. Hepatol Res, 2014, 44(14): E353-E359. doi: 10.1111/hepr.12315.
17.	劉雙池, 龐青, 談燚. 血小板在肝細胞癌發生和轉移中的研究進展. 中華普通外科學文獻 (電子版), 2021, 15(1): 66-69.
18.	夏曉露, 肖玉玲, 邱培, 等. 肝癌根治性切除術后復發的高危因素分析. 實用癌癥雜志, 2020, 35(11): 1875-1878.
19.	Capone M, Giannarelli D, Mallardo D, et al. Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab. J Immunother Cancer, 2018, 6(1): 74. doi: 10.1186/s40425-018-0383-1.
20.	Ji F, Liang Y, Fu SJ, et al. A novel and accurate predictor of survival for patients with hepatocellular carcinoma after surgical resection: the neutrophil to lymphocyte ratio (NLR) combined with the aspartate aminotransferase/platelet count ratio index (APRI). BMC Cancer, 2016, 16: 137. doi: 10.1186/s12885-016-2189-1.
21.	Wang D, Bai N, Hu X, et al. Preoperative inflammatory markers of NLR and PLR as indicators of poor prognosis in resectable HCC. PeerJ, 2019, 7: e7132. doi: 10.7717/peerj.7132.
22.	Zheng J, Cai J, Li H, et al. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as prognostic predictors for hepatocellular carcinoma patients with various treatments: a meta-analysis and systematic review. Cell Physiol Biochem, 2017, 44(3): 967-981.
23.	Chen Y, Zeng J, Guo P, et al. Prognostic significance of platelet-to-lymphocyte ratio (PLR) in extrahepatic metastasis of hepatocellular carcinoma after curative resection. Cancer Manag Res, 2021, 13: 1395-1405.
24.	Kwon HM, Moon YJ, Jung KW, et al. Neutrophil-to-lymphocyte ratio is a predictor of early graft dysfunction following living donor liver transplantation. Liver Int, 2019, 39(8): 1545-1556.
25.	Harimoto N, Yoshizumi T, Shimagaki T, et al. Inflammation-based prognostic score in patients with living donor liver transplantation for hepatocellular carcinoma. Anticancer Res, 2016, 36(10): 5537-5542.
26.	Lai Q, Melandro F, Larghi Laureiro Z, et al. Platelet-to-lymphocyte ratio in the setting of liver transplantation for hepatocellular cancer: a systematic review and meta-analysis. World J Gastroenterol, 2018, 24(15): 1658-1665.
27.	Ismael MN, Forde J, Milla E, et al. Utility of inflammatory markers in predicting hepatocellular carcinoma survival after liver transplantation. Biomed Res Int, 2019, 2019: 7284040. doi: 10.1155/2019/7284040.
28.	Ren A, Li Z, Zhang X, et al. Inflammation-based prognostic scores in patients with hepatitis B virus-related hepatocellular carcinoma after liver transplantation. J Hepatocell Carcinoma, 2020, 7: 101-106.
29.	Fan W, Zhang Y, Wang Y, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of survival and metastasis for recurrent hepatocellular carcinoma after transarterial chemoembolization. PLoS One, 2015, 10(3): e0119312. doi: 10.1371/journal.pone.0119312.
30.	Li S, Feng X, Cao G, et al. Prognostic significance of inflammatory indices in hepatocellular carcinoma treated with transarterial chemoembolization: a systematic review and meta-analysis. PLoS One, 2020, 15(3): e0230879. doi: 10.1371/journal.pone.0230879.
31.	He C, Zhang Y, Cai Z, et al. The prognostic and predictive value of the combination of the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio in patients with hepatocellular carcinoma who receive transarterial chemoembolization therapy. Cancer Manag Res, 2019, 11: 1391-1400.
32.	Guo L, Ren H, Pu L, et al. The prognostic value of inflammation factors in hepatocellular carcinoma patients with hepatic artery interventional treatments: a retrospective study. Cancer Manag Res, 2020, 12: 7173-7188.
33.	Chu MO, Shen CH, Chang TS, et al. Pretreatment inflammation-based markers predict survival outcomes in patients with early stage hepatocellular carcinoma after radiofrequency ablation. Sci Rep, 2018, 8(1): 16611. doi: 10.1038/s41598-018-34543-z.
34.	Chen K, Zhan MX, Hu BS, et al. Combination of the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio as a useful predictor for recurrence following radiofrequency ablation of hepatocellular carcinoma. Oncol Lett, 2018, 15(1): 315-323.
35.	Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 2008, 359(4): 378-390.
36.	Liu L, Gong Y, Zhang Q, et al. Prognostic roles of blood inflammatory markers in hepatocellular carcinoma patients taking sorafenib. A systematic review and meta-analysis. Front Oncol, 2020, 9: 1557. doi: 10.3389/fonc.2019.01557.
37.	Hong YM, Yoon KT, Hwang TH, et al. Changes in the neutrophil-to-lymphocyte ratio predict the prognosis of patients with advanced hepatocellular carcinoma treated with sorafenib. Eur J Gastroenterol Hepatol, 2019, 31(10): 1250-1255.
38.	Casadei-Gardini A, Dadduzio V, Rovesti G, et al. Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib. Medicine (Baltimore), 2020, 99(22): e19958. doi: 10.1097/MD.0000000000019958.

1. 中華人民共和國國家衛生健康委員會醫政醫管局. 原發性肝癌診療規范 (2019年版). 中華消化外科雜志, 2020, 19(1): 1-20.
2. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
3. Yang N, Han X, Yu J, et al. Hemoglobin, albumin, lymphocyte, and platelet score and neutrophil-to-lymphocyte ratio are novel significant prognostic factors for patients with small-cell lung cancer undergoing chemotherapy. J Cancer Res Ther, 2020, 16(5): 1134-1139.
4. Jonska-Gmyrek J, Gmyrek L, Zolciak-Siwinska A, et al. Pretreatment neutrophil to lymphocyte and platelet to lymphocyte ratios as predictive factors for the survival of cervical adenocarcinoma patients. Cancer Manag Res, 2018, 10: 6029-6038.
5. Yamazaki H, Sugino K, Matsuzu K, et al. Inflammatory biomarkers and dynamics of neutrophil-to-lymphocyte ratio in anaplastic thyroid carcinoma. Endocrine, 2020, 70(1): 115-122.
6. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet, 2001, 357(9255): 539-545.
7. Saha S, Biswas SK. Tumor-associated neutrophils show phenotypic and functional divergence in human lung cancer. Cancer Cell, 2016, 30(1): 11-13.
8. Rawat K, Syeda S, Shrivastava A. Neutrophil-derived granule cargoes: paving the way for tumor growth and progression. Cancer Metastasis Rev, 2021, 40(1): 221-244.
9. Schmidt H, Bastholt L, Geertsen P, et al. Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model. Br J Cancer, 2005, 93(3): 273-278.
10. 陳媛媛, 蔡晶, 江楚怡. 腫瘤浸潤淋巴細胞的過繼性T細胞療法在宮頸癌中的研究進展. 河南醫學研究, 2021, 30(1): 189-192.
11. Rosenberg SA, Spiess P, Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science, 1986, 233(4770): 1318-1321.
12. Paijens ST, Vledder A, de Bruyn M, et al. Tumor-infiltrating lymphocytes in the immunotherapy era. Cell Mol Immunol, 2021, 18(4): 842-859.
13. Sanchez K, Kim I, Chun B, et al. Multiplex immunofluorescence to measure dynamic changes in tumor-infiltrating lymphocytes and PD-L1 in early-stage breast cancer. Breast Cancer Res, 2021, 23(1): 2. doi: 10.1186/s13058-020-01378-4.
14. Klein S, Mauch C, Brinker K, et al. Tumor infiltrating lymphocyte clusters are associated with response to immune checkpoint inhibition in BRAF V600 E/K mutated malignant melanomas. Sci Rep, 2021, 11(1): 1834. doi: 10.1038/s41598-021-81330-4.
15. Yao J, Xi W, Chen X, et al. Mast cell density in metastatic renal cell carcinoma: Association with prognosis and tumour-infiltrating lymphocytes. Scand J Immunol, 2021, 93(4): e13006. doi: 10.1111/sji.13006.
16. Morimoto Y, Nouso K, Wada N, et al. Involvement of platelets in extrahepatic metastasis of hepatocellular carcinoma. Hepatol Res, 2014, 44(14): E353-E359. doi: 10.1111/hepr.12315.
17. 劉雙池, 龐青, 談燚. 血小板在肝細胞癌發生和轉移中的研究進展. 中華普通外科學文獻 (電子版), 2021, 15(1): 66-69.
18. 夏曉露, 肖玉玲, 邱培, 等. 肝癌根治性切除術后復發的高危因素分析. 實用癌癥雜志, 2020, 35(11): 1875-1878.
19. Capone M, Giannarelli D, Mallardo D, et al. Baseline neutrophil-to-lymphocyte ratio (NLR) and derived NLR could predict overall survival in patients with advanced melanoma treated with nivolumab. J Immunother Cancer, 2018, 6(1): 74. doi: 10.1186/s40425-018-0383-1.
20. Ji F, Liang Y, Fu SJ, et al. A novel and accurate predictor of survival for patients with hepatocellular carcinoma after surgical resection: the neutrophil to lymphocyte ratio (NLR) combined with the aspartate aminotransferase/platelet count ratio index (APRI). BMC Cancer, 2016, 16: 137. doi: 10.1186/s12885-016-2189-1.
21. Wang D, Bai N, Hu X, et al. Preoperative inflammatory markers of NLR and PLR as indicators of poor prognosis in resectable HCC. PeerJ, 2019, 7: e7132. doi: 10.7717/peerj.7132.
22. Zheng J, Cai J, Li H, et al. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio as prognostic predictors for hepatocellular carcinoma patients with various treatments: a meta-analysis and systematic review. Cell Physiol Biochem, 2017, 44(3): 967-981.
23. Chen Y, Zeng J, Guo P, et al. Prognostic significance of platelet-to-lymphocyte ratio (PLR) in extrahepatic metastasis of hepatocellular carcinoma after curative resection. Cancer Manag Res, 2021, 13: 1395-1405.
24. Kwon HM, Moon YJ, Jung KW, et al. Neutrophil-to-lymphocyte ratio is a predictor of early graft dysfunction following living donor liver transplantation. Liver Int, 2019, 39(8): 1545-1556.
25. Harimoto N, Yoshizumi T, Shimagaki T, et al. Inflammation-based prognostic score in patients with living donor liver transplantation for hepatocellular carcinoma. Anticancer Res, 2016, 36(10): 5537-5542.
26. Lai Q, Melandro F, Larghi Laureiro Z, et al. Platelet-to-lymphocyte ratio in the setting of liver transplantation for hepatocellular cancer: a systematic review and meta-analysis. World J Gastroenterol, 2018, 24(15): 1658-1665.
27. Ismael MN, Forde J, Milla E, et al. Utility of inflammatory markers in predicting hepatocellular carcinoma survival after liver transplantation. Biomed Res Int, 2019, 2019: 7284040. doi: 10.1155/2019/7284040.
28. Ren A, Li Z, Zhang X, et al. Inflammation-based prognostic scores in patients with hepatitis B virus-related hepatocellular carcinoma after liver transplantation. J Hepatocell Carcinoma, 2020, 7: 101-106.
29. Fan W, Zhang Y, Wang Y, et al. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictors of survival and metastasis for recurrent hepatocellular carcinoma after transarterial chemoembolization. PLoS One, 2015, 10(3): e0119312. doi: 10.1371/journal.pone.0119312.
30. Li S, Feng X, Cao G, et al. Prognostic significance of inflammatory indices in hepatocellular carcinoma treated with transarterial chemoembolization: a systematic review and meta-analysis. PLoS One, 2020, 15(3): e0230879. doi: 10.1371/journal.pone.0230879.
31. He C, Zhang Y, Cai Z, et al. The prognostic and predictive value of the combination of the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio in patients with hepatocellular carcinoma who receive transarterial chemoembolization therapy. Cancer Manag Res, 2019, 11: 1391-1400.
32. Guo L, Ren H, Pu L, et al. The prognostic value of inflammation factors in hepatocellular carcinoma patients with hepatic artery interventional treatments: a retrospective study. Cancer Manag Res, 2020, 12: 7173-7188.
33. Chu MO, Shen CH, Chang TS, et al. Pretreatment inflammation-based markers predict survival outcomes in patients with early stage hepatocellular carcinoma after radiofrequency ablation. Sci Rep, 2018, 8(1): 16611. doi: 10.1038/s41598-018-34543-z.
34. Chen K, Zhan MX, Hu BS, et al. Combination of the neutrophil to lymphocyte ratio and the platelet to lymphocyte ratio as a useful predictor for recurrence following radiofrequency ablation of hepatocellular carcinoma. Oncol Lett, 2018, 15(1): 315-323.
35. Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med, 2008, 359(4): 378-390.
36. Liu L, Gong Y, Zhang Q, et al. Prognostic roles of blood inflammatory markers in hepatocellular carcinoma patients taking sorafenib. A systematic review and meta-analysis. Front Oncol, 2020, 9: 1557. doi: 10.3389/fonc.2019.01557.
37. Hong YM, Yoon KT, Hwang TH, et al. Changes in the neutrophil-to-lymphocyte ratio predict the prognosis of patients with advanced hepatocellular carcinoma treated with sorafenib. Eur J Gastroenterol Hepatol, 2019, 31(10): 1250-1255.
38. Casadei-Gardini A, Dadduzio V, Rovesti G, et al. Utility of neutrophil-to-lymphocyte ratio to identify long-term survivors among HCC patients treated with sorafenib. Medicine (Baltimore), 2020, 99(22): e19958. doi: 10.1097/MD.0000000000019958.

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Application progress of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in various treatment methods of hepatocellular carcinoma

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