The aim of the present study was to determine the most meaningful preoperative prognostic factor of cancer-related death in ovarian cancer patients by comparing potentially prognostic systemic inflammatory response (SIR) markers. The levels of fibrinogen, albumin, C-reactive protein (CRP), and serum cancer antigen-125 (CA-125) and the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were evaluated in 190 ovarian cancer patients to identify predictors of overall survival (OS) and progression-free survival (PFS) using univariate and multivariate analyses. Patients with a PLR >203 had a shorter PFS and OS than the patients in PLR ≤203 group (11 vs. 24 months and 28 vs. 64 months). Univariate analyses revealed that tumor stage, postoperative residual tumor mass, ascites, and the levels of all SIR markers were associated with PFS and OS. Multivariate analysis revealed that PLR was independently associated with PFS (hazard ratio [HR] 1.852, 95 % confidence interval [CI] 1.271–2.697, P = 0.001) and OS (HR 2.158, 95 %CI 1.468–3.171, P < 0.001), as well as tumor stage and postoperative residual tumor mass. In contrast, fibrinogen remained significant only for PFS (HR 1.724, 95 %CI 1.197–2.482, P = 0.003). Patients with a PLR >203 were more prone to have advanced tumor stage (P = 0.002), postoperative residual tumor mass >2 cm (P = 0.032), malignant ascites (P < 0.001), and all the other elevated SIR markers (P < 0.001). Preoperative PLR is superior to other SIR markers (CA-125, NLR, fibrinogen, CRP, and albumin) as a predictor of survival in ovarian cancer patients.
Platelet/lymphocyte ratio Prognostic factor Systemic inflammatory response markers Ovarian cancer
This is a preview of subscription content, log in to check access.
Wei-wei Zhang and Ke-jun Liu contributed equally to this work. The authors would like to thank doctors, nurses, patients, and their family members for their kindness to support our study.
The Department of the Science and Technology Planning Project Fund of Guangdong Province in China (2011B031800042).
Conflicts of interest
Cohen CA, Shea AA, Heffron CL, Schmelz EM, Roberts PC. The parity-associated microenvironmental niche in the omental fat band is refractory to ovarian cancer metastasis. Cancer Prev Res (Phila). 2013;6:1182–93.CrossRefGoogle Scholar
Hirashima K, Watanabe M, Shigaki H, Imamura Y, Ida S, Iwatsuki M, et al. Prognostic significance of the modified Glasgow prognostic score in elderly patients with gastric cancer. J Gastroenterol. 2014;49:1040–6.CrossRefPubMedGoogle Scholar
Wu N, Chen G, Hu H, Pang L, Chen Z. Low pretherapeutic serum albumin as a risk factor for poor outcome in esophageal squamous cell carcinomas. Nutr Cancer. 2015;67:481–5.CrossRefPubMedGoogle Scholar
Oh BS, Jang JW, Kwon JH, You CR, Chung KW, Kay CS, et al. Prognostic value of C-reactive protein and neutrophil-to-lymphocyte ratio in patients with hepatocellular carcinoma. BMC Cancer. 2013;13:78.CrossRefPubMedPubMedCentralGoogle Scholar
Chua W, Charles KA, Baracos VE, Clarke SJ. Neutrophil/lymphocyte ratio predicts chemotherapy outcomes in patients with advanced colorectal cancer. Br J Cancer. 2011;104:1288–95.CrossRefPubMedPubMedCentralGoogle Scholar
Chen Q, Yang LX, Li XD, Yin D, Shi SM, Chen EB, et al. The elevated preoperative neutrophil-to-lymphocyte ratio predicts poor prognosis in intrahepatic cholangiocarcinoma patients undergoing hepatectomy. Tumour Biol. 2015. doi:10.1007/s13277-015-3188-6.
Bishara S, Griffin M, Cargill A, Bali A, Gore ME, Kaye SB, et al. Pre-treatment white blood cell subtypes as prognostic indicators in ovarian cancer. Eur J Obstet Gynecol Reprod Biol. 2008;138:71–5.CrossRefPubMedGoogle Scholar
Kisielewski R, Tolwinska A, Mazurek A, Laudanski P. Inflammation and ovarian cancer—current views. Ginekol Pol. 2013;84:293–7.CrossRefPubMedGoogle Scholar
Petri AL, Hogdall E, Christensen IJ, Kjaer SK, Blaakaer J, Hogdall CK. Preoperative CA125 as a prognostic factor in stage I epithelial ovarian cancer. APMIS. 2006;114:359–63.CrossRefPubMedGoogle Scholar
Asher V, Lee J, Bali A. Preoperative serum albumin is an independent prognostic predictor of survival in ovarian cancer. Med Oncol. 2012;29:2005–9.CrossRefPubMedGoogle Scholar
Hefler LA, Concin N, Hofstetter G, Marth C, Mustea A, Sehouli J, et al. Serum C-reactive protein as independent prognostic variable in patients with ovarian cancer. Clin Cancer Res. 2008;14:710–4.CrossRefPubMedGoogle Scholar
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;132:542–50.CrossRefPubMedPubMedCentralGoogle Scholar
Asher V, Lee J, Innamaa A, Bali A. Preoperative platelet lymphocyte ratio as an independent prognostic marker in ovarian cancer. Clin Transl Oncol. 2011;13:499–503.CrossRefPubMedGoogle Scholar
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;14:979–85.CrossRefPubMedGoogle Scholar
Azab B, Shah N, Radbel J, Tan P, Bhatt V, Vonfrolio S, et al. Pretreatment neutrophil/lymphocyte ratio is superior to platelet/lymphocyte ratio as a predictor of long-term mortality in breast cancer patients. Med Oncol. 2013;30:432.CrossRefPubMedGoogle Scholar
He W, Yin C, Guo G, Jiang C, Wang F, Qiu H, et al. Initial neutrophil lymphocyte ratio is superior to platelet lymphocyte ratio as an adverse prognostic and predictive factor in metastatic colorectal cancer. Med Oncol. 2013;30:439.CrossRefPubMedGoogle Scholar
Piver MS, Lele SB, Marchetti DL, Baker TR, Tsukada Y, Emrich LJ. The impact of aggressive debulking surgery and cisplatin-based chemotherapy on progression-free survival in stage III and IV ovarian carcinoma. J Clin Oncol. 1988;6:983–9.CrossRefPubMedGoogle Scholar
Makar AP, Baekelandt M, Trope CG, Kristensen GB. The prognostic significance of residual disease, FIGO substage, tumor histology, and grade in patients with FIGO stage III ovarian cancer. Gynecol Oncol. 1995;56:175–80.CrossRefPubMedGoogle Scholar
Raungkaewmanee S, Tangjitgamol S, Manusirivithaya S, Srijaipracharoen S, Thavaramara T. Platelet to lymphocyte ratio as a prognostic factor for epithelial ovarian cancer. J Gynecol Oncol. 2012;23:265–73.CrossRefPubMedPubMedCentralGoogle Scholar
Yildirim M, Yildiz M, Duman E, Goktas S, Kaya V. Prognostic importance of the nutritional status and systemic inflammatory response in non-small cell lung cancer. J Buon. 2013;18:728–32.PubMedGoogle Scholar
Dirican A, Kucukzeybek Y, Somali I, Erten C, Demir L, Can A, et al. The association of hematologic parameters on the prognosis of patients with metastatic renal cell carcinoma. J Buon. 2013;18:413–9.PubMedGoogle Scholar
Hong C, Wei Y, Jiang J, Zhao C, Liang G, Wang G, et al. Associations between lifestyles and neutrophil-lymphocyte and platelet-lymphocyte ratios in colorectal cancer. Asia Pac J Clin Oncol. 2013;10:168–74. doi: 10.1111/ajco.12080.Google Scholar
Garcea G, Ladwa N, Neal CP, Metcalfe MS, Dennison AR, Berry DP. Preoperative neutrophil-to-lymphocyte ratio (NLR) is associated with reduced disease-free survival following curative resection of pancreatic adenocarcinoma. World J Surg. 2011;35:868–72.CrossRefPubMedGoogle Scholar
Smith RA, Ghaneh P, Sutton R, Raraty M, Campbell F, Neoptolemos JP. Prognosis of resected ampullary adenocarcinoma by preoperative serum CA19-9 levels and platelet-lymphocyte ratio. J Gastrointest Surg. 2008;12:1422–8.CrossRefPubMedGoogle Scholar
Wang D, Yang JX, Cao DY, Wan XR, Feng FZ, Huang HF, et al. Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma. Onco Targets Ther. 2013;6:211–6.PubMedPubMedCentralGoogle Scholar
Allensworth SK, Langstraat CL, Martin JR, Lemens MA, McGree ME, Weaver AL, et al. Evaluating the prognostic significance of preoperative thrombocytosis in epithelial ovarian cancer. Gynecol Oncol. 2013;130:499–504.CrossRefPubMedPubMedCentralGoogle Scholar
Alexandrakis MG, Passam FH, Moschandrea IA, Christophoridou AV, Pappa CA, Coulocheri SA, et al. Levels of serum cytokines and acute phase proteins in patients with essential and cancer-related thrombocytosis. Am J Clin Oncol. 2003;26:135–40.CrossRefPubMedGoogle Scholar
Suzuki K, Aiura K, Ueda M, Kitajima M. The influence of platelets on the promotion of invasion by tumor cells and inhibition by antiplatelet agents. Pancreas. 2004;29:132–40.CrossRefPubMedGoogle Scholar
Riesco A. Five-year cancer cure: relation to total amount of peripheral lymphocytes and neutrophils. Cancer-Am Cancer Soc. 1970;25:135–40.Google Scholar
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;58:15–23.CrossRefPubMedGoogle Scholar
Yigit R, Massuger LF, Figdor CG, Torensma R. Ovarian cancer creates a suppressive microenvironment to escape immune elimination. Gynecol Oncol. 2010;117:366–72.CrossRefPubMedGoogle Scholar
Ruka W, Rutkowski P, Kaminska J, Rysinska A, Steffen J. Alterations of routine blood tests in adult patients with soft tissue sarcomas: relationships to cytokine serum levels and prognostic significance. Ann Oncol. 2001;12:1423–32.CrossRefPubMedGoogle Scholar
Shen GH, Ghazizadeh M, Kawanami O, Shimizu H, Jin E, Araki T, et al. Prognostic significance of vascular endothelial growth factor expression in human ovarian carcinoma. Br J Cancer. 2000;83:196–203.CrossRefPubMedPubMedCentralGoogle Scholar
Huang Y, Chen X, Dikov MM, Novitskiy SV, Mosse CA, Yang L, et al. Distinct roles of VEGFR-1 and VEGFR-2 in the aberrant hematopoiesis associated with elevated levels of VEGF. Blood. 2007;110:624–31.CrossRefPubMedPubMedCentralGoogle Scholar