Prognostic value of neutrophil-to-lymphocyte ratio and fibrinogen levels in ovarian cancer

  • Roudhona Rosaudyn Department Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia
  • Faradillah Mutiani Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia https://orcid.org/0000-0002-5312-5822
  • Indra Yuliati Department Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia
  • Birama Robby Indraprasta Department Obstetrics and Gynecology, Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia https://orcid.org/0000-0002-4514-9672
DOI: https://doi.org/10.13181/mji.oa.236880
Keywords: meta-analysis, ovarian cancer, prognosis, progression-free survival, survival analysis
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Abstract

BACKGROUND High neutrophil-to-lymphocyte ratio (NLR) and fibrinogen levels have been associated with mortality in several malignancies. However, the studies on the association between NLR or fibrinogen levels and ovarian cancer prognosis are inconsistent. This study aimed to investigate the prognostic roles of NLR and fibrinogen in ovarian cancer.

METHODS A systematic search of electronic databases was performed to analyze studies on the association of pre-treatment NLR and fibrinogen levels with overall survival (OS) and progression-free survival (PFS) among patients with ovarian cancer. The hazard ratio (HR) and corresponding 95% confidence intervals [CIs] were analyzed. All statistical analyses were done using RevMan version 5.4 (Cochrane, United Kingdom).

RESULTS A total of 7,312 patients from 27 studies were included. The median cut-off for high NLR was 3.6 for OS among 17 studies and 3.23 for PFS among 11 studies reporting an NLR HR. The median cut-off for fibrinogen levels was 4.0 in 9 studies reporting fibrinogen levels HR. High NLR was associated with lower OS (HR 1.35, 95% CI 1.18 to 1.55, p<0.0001, I2 = 76%) and PFS (HR 1.35, 95% CI 1.14 to 1.60, p = 0.0005, I2 = 71%). High fibrinogen levels were associated with lower OS (HR 1.44, 95% CI 1.14 to 1.82, p = 0.002, I2 = 81%) and PFS (HR 1.34, 95% CI 1.17 to 1.55, p<0.0001, I2 = 15%). This association occurred in all ovarian cancer types.

CONCLUSIONS High pre-treatment NLR and plasma fibrinogen levels were related to poor OS and PFS in ovarian cancer.

References

  1. Huang J, Chan WC, Ngai CH, Lok V, Zhang L, Lucero-Prisno DE 3rd, et al. Worldwide burden, risk factors, and temporal trends of ovarian cancer: a global study. Cancers (Basel). 2022;14(9):2230. https://doi.org/10.3390/cancers14092230

  2. Arora T, Mullangi S, Lekkala MR. Ovarian cancer. [updated 2023 Jun 18]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567760/.

  3. American Cancer Society. Cancer facts & figures 2022. Atlanta: American Cancer Society; 2022. p. 1-80.

  4. Baldwin LA, Huang B, Miller RW, Tucker T, Goodrich ST, Podzielinski I, et al. Ten-year relative survival for epithelial ovarian cancer. Obstet Gynecol. 2012;120(3):612-8. https://doi.org/10.1097/AOG.0b013e318264f794

  5. PDQ Adult Treatment Editorial Board. Ovarian epithelial, fallopian tube, and primary peritoneal cancer treatment (PDQ®): health professional version. 2023. In: PDQ Cancer Information Summaries. Bethesda (MD): National Cancer Institute (US); 2002.

  6. Howard R, Kanetsky PA, Egan KM. Exploring the prognostic value of the neutrophil-to-lymphocyte ratio in cancer. Sci Rep. 2019;9(19673). https://doi.org/10.1038/s41598-019-56218-z

  7. 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. https://doi.org/10.1177/1533033818791500

  8. Gago-Dominguez M, Matabuena M, Redondo CM, Patel SP, Carracedo A, Ponte SM, et al. Neutrophil to lymphocyte ratio and breast cancer risk: analysis by subtype and potential interactions. Sci Rep. 2020;10(1):13203. Erratum in: Sci Rep. 2020;10(1):20641. https://doi.org/10.1038/s41598-020-70077-z

  9. Cupp MA, Cariolou M, Tzoulaki I, Aune D, Evangelou E, Berlanga-Taylor AJ. Neutrophil to lymphocyte ratio and cancer prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies. BMC Med. 2020;18(1):360. https://doi.org/10.1186/s12916-020-01817-1

  10. Zhang X, Long Q. Elevated serum plasma fibrinogen is associated with advanced tumor stage and poor survival in hepatocellular carcinoma patients. Medicine (Baltimore). 2017;96(17):e6694. https://doi.org/10.1097/MD.0000000000006694

  11. Lin Y, Liu Z, Qiu Y, Zhang J, Wu H, Liang R, et al. Clinical significance of plasma D-dimer and fibrinogen in digestive cancer: a systematic review and meta-analysis. Eur J Surg Oncol. 2018;44(10):1494-503. https://doi.org/10.1016/j.ejso.2018.07.052

  12. Yu X, Hu F, Yao Q, Li C, Zhang H, Xue Y. Serum fibrinogen levels are positively correlated with advanced tumor stage and poor survival in patients with gastric cancer undergoing gastrectomy: a large cohort retrospective study. BMC Cancer. 2016;16:480. https://doi.org/10.1186/s12885-016-2510-z

  13. Wang YQ, Jin C, Zheng HM, Zhou K, Shi BB, Zhang Q, et al. A novel prognostic inflammation score predicts outcomes in patients with ovarian cancer. Clin Chim Acta. 2016;456:163-9. https://doi.org/10.1016/j.cca.2016.03.013

  14. Henriksen JR, Nederby L, Donskov F, Waldstrøm M, Adimi P, Jakobsen A, et al. Prognostic significance of baseline T cells, B cells and neutrophil-lymphocyte ratio (NLR) in recurrent ovarian cancer treated with chemotherapy. J Ovarian Res. 2020;13(1):59. https://doi.org/10.1186/s13048-020-00661-4

  15. Marchetti C, D'Indinosante M, Bottoni C, Di Ilio C, Di Berardino S, Costantini B, et al. NLR and BRCA mutational status in patients with high grade serous advanced ovarian cancer. Sci Rep. 2021;11(1):11125. https://doi.org/10.1038/s41598-021-90361-w

  16. Asher V, Lee J, Innamaa A, Bali A. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol. 2011;13(7):499-503. https://doi.org/10.1007/s12094-011-0687-9

  17. Komura N, Mabuchi S, Yokoi E, Kozasa K, Kuroda H, Sasano T, et al. Comparison of clinical utility between neutrophil count and neutrophil-lymphocyte ratio in patients with ovarian cancer: a single institutional experience and a literature review. Int J Clin Oncol. 2018;23(1):104-13. https://doi.org/10.1007/s10147-017-1180-4

  18. Baert T, Van Camp J, Vanbrabant L, Busschaert P, Laenen A, Han S, et al. Influence of CA125, platelet count and neutrophil to lymphocyte ratio on the immune system of ovarian cancer patients. Gynecol Oncol. 2018;150(1):31-7. https://doi.org/10.1016/j.ygyno.2018.05.004

  19. Miao Y, Yan Q, Li S, Li B, Feng Y. Neutrophil to lymphocyte ratio and platelet to lymphocyte ratio are predictive of chemotherapeutic response and prognosis in epithelial ovarian cancer patients treated with platinum-based chemotherapy. Cancer Biomark. 2016;17(1):33-40. https://doi.org/10.3233/CBM-160614

  20. Zhou M, Li L, Wang X, Wang C, Wang D. Neutrophil-to-lymphocyte ratio and platelet count predict long-term outcome of stage iiic epithelial ovarian cancer. Cell Physiol Biochem. 2018;46(1):178-86. https://doi.org/10.1159/000488420

  21. Badora-Rybicka A, Nowara E, Starzyczny-Słota D. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio before chemotherapy as potential prognostic factors in patients with newly diagnosed epithelial ovarian cancer. ESMO Open. 2016;1(2):e000039. https://doi.org/10.1136/esmoopen-2016-000039

  22. Salman L, Sabah G, Jakobson-Setton A, Raban O, Yeoshoua E, Eitan R. Neutrophil-to-lymphocyte ratio as a prognostic factor in advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy. Int J Gynaecol Obstet. 2020;148(1):102-6. https://doi.org/10.1002/ijgo.12986

  23. Jeerakornpassawat D, Suprasert P. Potential predictors for chemotherapeutic response and prognosis in epithelial ovarian, fallopian tube and primary peritoneal cancer patients treated with platinum-based chemotherapy. Obstet Gynecol Sci. 2020;63(1):55-63. https://doi.org/10.5468/ogs.2020.63.1.55

  24. Cho H, Hur HW, Kim SW, Kim SH, Kim JH, Kim YT, et al. Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol Immunother. 2009;58(1):15-23. https://doi.org/10.1007/s00262-008-0516-3

  25. Feng Z, Wen H, Bi R, Ju X, Chen X, Yang W, et al. Preoperative neutrophil-to-lymphocyte ratio as a predictive and prognostic factor for high-grade serous ovarian cancer. PLoS One. 2016;11(5):e0156101. https://doi.org/10.1371/journal.pone.0156101

  26. Wang Y, Liu P, Xu Y, Zhang W, Tong L, Guo Z, et al. Preoperative neutrophil-to-lymphocyte ratio predicts response to first-line platinum-based chemotherapy and prognosis in serous ovarian cancer. Cancer Chemother Pharmacol. 2015;75(2):255-62. https://doi.org/10.1007/s00280-014-2622-6

  27. Li Z, Hong N, Robertson M, Wang C, Jiang G. Preoperative red cell distribution width and neutrophil-to-lymphocyte ratio predict survival in patients with epithelial ovarian cancer. Sci Rep. 2017;7:43001. https://doi.org/10.1038/srep43001

  28. Kim YJ, Lee I, Chung YS, Nam E, Kim S, Kim SW, et al. Pretreatment neutrophil-to-lymphocyte ratio and its dynamic change during neoadjuvant chemotherapy as poor prognostic factors in advanced ovarian cancer. Obstet Gynecol Sci. 2018;61(2):227-34. https://doi.org/10.5468/ogs.2018.61.2.227

  29. John-Olabode SO, Okunade KS, Olorunfemi G, Soibi-Harry A, Rimi G, Osunwusi B, et al. Pretreatment neutrophil-to-lymphocyte ratio: a prognostic biomarker of survival in patients with epithelial ovarian cancer. Cureus. 2021;13(7):e16429. https://doi.org/10.7759/cureus.16429

  30. Williams KA, Labidi-Galy SI, Terry KL, Vitonis AF, Welch WR, Goodman A, et al. Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer. Gynecol Oncol. 2014;132(3):542-50. https://doi.org/10.1016/j.ygyno.2014.01.026

  31. Qiu J, Yu Y, Fu Y, Ye F, Xie X, Lu W. Preoperative plasma fibrinogen, platelet count and prognosis in epithelial ovarian cancer. J Obstet Gynaecol Res. 2012;38(4):651-7. https://doi.org/10.1111/j.1447-0756.2011.01780.x

  32. Li Y, Yang JN, Cheng SS, Wang Y. Prognostic significance of FA score based on plasma fibrinogen and serum albumin in patients with epithelial ovarian cancer. Cancer Manag Res. 2019;11:7697-705. https://doi.org/10.2147/CMAR.S211524

  33. Polterauer S, Grimm C, Seebacher V, Concin N, Marth C, Tomovski C, et al. Plasma fibrinogen levels and prognosis in patients with ovarian cancer: a multicenter study. Oncologist. 2009;14(10):979-85. https://doi.org/10.1634/theoncologist.2009-0079

  34. Hu Q, Hada A, Han L. Platelet count as a biomarker for monitoring treatment response and disease recurrence in recurrent epithelial ovarian cancer. J Ovarian Res. 2020;13(78). https://doi.org/10.1186/s13048-020-00682-z

  35. Feng Z, Wen H, Bi R, Duan Y, Yang W, Wu X. Thrombocytosis and hyperfibrinogenemia are predictive factors of clinical outcomes in high-grade serous ovarian cancer patients. BMC Cancer. 2016;16:43. https://doi.org/10.1186/s12885-016-2070-2

  36. Zhang WW, Liu KJ, Hu GL, Liang WJ. Preoperative platelet/lymphocyte ratio is a superior prognostic factor compared to other systemic inflammatory response markers in ovarian cancer patients. Tumour Biol. 2015;36(11):8831-7. https://doi.org/10.1007/s13277-015-3533-9

  37. Man YN, Wang YN, Hao J, Liu X, Liu C, Zhu C, et al. Pretreatment plasma D-dimer, fibrinogen, and platelet levels significantly impact prognosis in patients with epithelial ovarian cancer independently of venous thromboembolism. Int J Gynecol Cancer. 2015;25(1):24-32. https://doi.org/10.1097/IGC.0000000000000303

  38. Liu P, Wang Y, Tong L, Xu Y, Zhang W, Guo Z, et al. Elevated preoperative plasma D-dimer level is a useful predictor of chemoresistance and poor disease outcome for serous ovarian cancer patients. Cancer Chemother Pharmacol. 2015;76(6):1163-71. https://doi.org/10.1007/s00280-015-2900-y

  39. Luo Y, Kim HS, Kim M, Lee M, Song YS. Elevated plasma fibrinogen levels and prognosis of epithelial ovarian cancer: a cohort study and meta-analysis. J Gynecol Oncol. 2017;28(3):e36. https://doi.org/10.3802/jgo.2017.28.e36

  40. Wang H, Zhao J, Zhang M, Han L, Wang M, Xingde L. The combination of plasma fibrinogen and neutrophil lymphocyte ratio (F-NLR) is a predictive factor in patients with resectable non small cell lung cancer. J Cell Physiol. 2018;233(5):4216-24. https://doi.org/10.1002/jcp.26239

  41. Kijima T, Arigami T, Uchikado Y, Uenosono Y, Kita Y, Owaki T, et al. Combined fibrinogen and neutrophil-lymphocyte ratio as a prognostic marker of advanced esophageal squamous cell carcinoma. Cancer Sci. 2017;108(2):193-9. https://doi.org/10.1111/cas.13127

  42. Diakos CI, Charles KA, McMillan DC, Clarke SJ. Cancer-related inflammation and treatment effectiveness. Lancet Oncol. 2014;15(11):e493-503. https://doi.org/10.1016/S1470-2045(14)70263-3

  43. Song XD, Wang YN, Zhang AL, Liu B. Advances in research on the interaction between inflammation and cancer. J Int Med Res. 2020;48(4):300060519895347. https://doi.org/10.1177/0300060519895347

  44. Nøst TH, Alcala K, Urbarova I, Byrne KS, Guida F, Sandanger TM, et al. Systemic inflammation markers and cancer incidence in the UK Biobank. Eur J Epidemiol. 2021;36(8):841-8. https://doi.org/10.1007/s10654-021-00752-6

  45. Dolan RD, McSorley ST, Horgan PG, Laird B, McMillan DC. The role of the systemic inflammatory response in predicting outcomes in patients with advanced inoperable cancer: Systematic review and meta-analysis. Crit Rev Oncol Hematol. 2017;116:134-46. https://doi.org/10.1016/j.critrevonc.2017.06.002

  46. Sylman JL, Mitrugno A, Atallah M, Tormoen GW, Shatzel JJ, Tassi Yunga S, et al. The predictive value of inflammation-related peripheral blood measurements in cancer staging and prognosis. Front Oncol. 2018;8:78. https://doi.org/10.3389/fonc.2018.00078

  47. Uribe-Querol E, Rosales C. Neutrophils in cancer: two sides of the same coin. J Immunol Res. 2015;2015:983698. https://doi.org/10.1155/2015/983698

  48. Corbeau I, Jacot W, Guiu S. Neutrophil to lymphocyte ratio as prognostic and predictive factor in breast cancer patients: a systematic review. Cancers (Basel). 2020;12(4):958. https://doi.org/10.3390/cancers12040958

  49. Ethier JL, Desautels DN, Templeton AJ, Oza A, Amir E, Lheureux S. Is the neutrophil-to-lymphocyte ratio prognostic of survival outcomes in gynecologic cancers? A systematic review and meta-analysis. Gynecol Oncol. 2017;145(3):584-94. https://doi.org/10.1016/j.ygyno.2017.02.026

  50. Sheng L, Luo M, Sun X, Lin N, Mao W, Su D. Serum fibrinogen is an independent prognostic factor in operable nonsmall cell lung cancer. Int J Cancer. 2013;133(11):2720-5. https://doi.org/10.1002/ijc.28284

  51. Zheng S, Shen J, Jiao Y, Liu Y, Zhang C, Wei M, et al. Platelets and fibrinogen facilitate each other in protecting tumor cells from natural killer cytotoxicity. Cancer Sci. 2009;100(5):859-65. https://doi.org/10.1111/j.1349-7006.2009.01115.x

  52. Gropp C, Egbring R, Havemann K. Fibrinogen split products, antiproteases and granulocytic elastase in patients with lung cancer. Eur J Cancer (1965). 1980;16(5):679-85. https://doi.org/10.1016/0014-2964(80)90209-1

  53. Yin X, Wu L, Yang H, Yang H. Prognostic significance of neutrophil-lymphocyte ratio (NLR) in patients with ovarian cancer: a systematic review and meta-analysis. Medicine (Baltimore). 2019;98(45):e17475. https://doi.org/10.1097/MD.0000000000017475

  54. Liontos M, Andrikopoulou A, Koutsoukos K, Markellos C, Skafida E, Fiste O, et al. Neutrophil-to-lymphocyte ratio and chemotherapy response score as prognostic markers in ovarian cancer patients treated with neoadjuvant chemotherapy. J Ovarian Res. 2021;14(1):148. https://doi.org/10.1186/s13048-021-00902-0

  55. Marchetti C, Romito A, Musella A, Santo G, Palaia I, Perniola G, et al. Combined plasma fibrinogen and neutrophil lymphocyte ratio in ovarian cancer prognosis may play a role? Int J Gynecol Cancer. 2018;28:939-44. https://doi.org/10.1097/IGC.0000000000001233

Published
2023-10-02
How to Cite
1.
Rosaudyn R, Mutiani F, Yuliati I, Indraprasta BR. Prognostic value of neutrophil-to-lymphocyte ratio and fibrinogen levels in ovarian cancer. Med J Indones [Internet]. 2023Oct.2 [cited 2024May22];32(2):86-7. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/6880
Issue
Vol. 32 No. 2 (2023): June
Section
Clinical Research

Copyright (c) 2023 Roudhona Rosaudyn, Faradillah Mutiani, Indra Yuliati, Birama Robby Indraprasta

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