Assessment of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and platelet count as predictors of long-term outcome after R0 resection for colorectal cancer

Corrado Pedrazzani, Guido Mantovani, Eduardo Fernandes, Fabio Bagante, Gian Luca Salvagno, Niccolò Surci, Tommaso Campagnaro, Andrea Ruzzenente, Elisa Danese, Giuseppe Lippi, Alfredo Guglielmi, Corrado Pedrazzani, Guido Mantovani, Eduardo Fernandes, Fabio Bagante, Gian Luca Salvagno, Niccolò Surci, Tommaso Campagnaro, Andrea Ruzzenente, Elisa Danese, Giuseppe Lippi, Alfredo Guglielmi

Abstract

Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and platelet count (PC) were shown to be prognostic in several solid malignancies. We analysed 603 R0 resected patients to assess whether NLR, PLR and PC correlate with other well-known prognostic factors and survival of patients with colorectal cancer (CRC). Receiver operating characteristic (ROC) curve analysis was performed to define cut-off values for high and low ratios of these indices. Univariate and multivariate analysis were used to determine the prognostic value of NLR, PLR and PC for overall and cancer-related survival. The distribution of NLR, PLR and PC in CRC patients was compared with 5270 healthy blood donors. The distribution of NLR, PLR and PC was significantly different between CRC patients and controls (all p < 0.05). A significant but heterogeneous association was found between the main CRC prognostic factors and high values of NLR, PLR and PC. Survival appeared to be worse in patients with high NLR with cancers in AJCC/UICC TNM Stages I-IV; nonetheless its prognostic value was not confirmed for cancer-related survival in multivariate analysis. After stratification of patients according to AJCC/UICC TNM stages, high PC value was significantly correlated with overall and cancer-related survival in TNM stage IV patients.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Distribution of (a) NLR, (b) PLR, and (c) PC stratified by study and control groups.
Figure 2
Figure 2
Kaplan-Meier curves for (a) overall survival (p < 0.001) and (b) cancer-related survival (p = 0.022) stratified by NLR.
Figure 3
Figure 3
Kaplan-Meier curves for (a) overall survival (p = 0.002) and (b) cancer-related survival (p = 0.041) stratified by PC in AJCC/UICC TNM Stage IV.

References

    1. Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2014;59:366–378. doi: 10.3322/caac.20038.
    1. Gu L, et al. Prognostic value of preoperative response biomarkers in patients with sarcomatoid renal cell carcinoma and the establishment of a nomogram. Sci Rep. 2016;6:23846. doi: 10.1038/srep23846.
    1. Pine JK, et al. Systemic neutrophil-to-lymphocyte ratio in colorectal cancer: the relationship to patient survival, tumour biology and local lymphocytic response to tumour. Br J Cancer. 2015;113:204–211. doi: 10.1038/bjc.2015.87.
    1. Passardi A, et al. Inflammatory indexes as predictors of prognosis and bevacizumab efficacy in patients with metastatic colorectal cancer. Oncotarget. 2016;7:33210–33219.
    1. Zhao W, et al. Pretreatment neutrophil-to-lymphocyte ratio and its dynamic changes are associated with overall survival in advanced cancer patients undergoing palliative care. Sci Rep. 2016;6:31394. doi: 10.1038/srep31394.
    1. Templeton AJ, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Canc Inst. 2014;6:dju124–dju124. doi: 10.1093/jnci/dju124.
    1. Pedrazzani C, et al. Elevated fibrinogen plasma level is not an independent predictor of poor prognosis in a large cohort of Western patients undergoing surgery for colorectal cancer. World J Gastroenterol. 2016;22:9994–10001. doi: 10.3748/wjg.v22.i45.9994.
    1. Long Y, et al. Prognostic significance of pretreatment elevated platelet count in patients with colorectal cancer. Oncotarget. 2016;7:81849–81861.
    1. Verheul HM, et al. Platelet and coagulation activation with vascular endothelial growth factor generation in soft tissue sarcomas. Clin Cancer Res. 2000;6:166–171.
    1. Ikeda M, et al. Poor prognosis associated with thrombocytosis in patients with gastric cancer. Ann Surg Oncol. 2002;9:287–291. doi: 10.1007/BF02573067.
    1. Dubernard V, Arbeille BB, Lemesle MB, Legrand C. Evidence for an alpha-granular pool of the cytoskeletal protein alpha-actinin in human platelets that redistributes with the adhesive glycoprotein thrombospondin-1 during the exocytotic process. Arterioscler Thromb Vasc Biol. 1997;17:2293–2305. doi: 10.1161/01.ATV.17.10.2293.
    1. Xiao Q, et al. The preoperative neutrophil-to-lymphocyte ratio is a novel immune parameter for the prognosis of esophageal basaloid squamous cell carcinoma. PLoS One. 2016;11:0168299.
    1. Yodying H, et al. Prognostic significance of neutrophil-to lymphocyte ratio and platelet-to-lymphocyte ratio in oncologic outcomes of esophageal cancer: a systematic review ant meta-analysis. Ann Surg Oncol. 2016;23:646–654. doi: 10.1245/s10434-015-4869-5.
    1. McNamara MG, et al. Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer. Eur J Cancer. 2014;50:1581–1589. doi: 10.1016/j.ejca.2014.02.015.
    1. Gemenetzis, G. et al. Neutrophil-to-lymphocyte ratio is a predictive marker for invasive malignancy in intraductal papillary mucinous neoplasms of the pancreas. Ann Surg. (2016) [Epub ahead of print].
    1. Sciarra A, et al. Prognostic value of inflammation in prostate cancer progression and response to therapeutic: a critical review. J Inflamm. 2016;13:12950. doi: 10.1186/s12950-016-0143-2.
    1. Turner N, et al. Primary tumor resection in patients with metastatic colorectal cancer is associated with reversal of systemic inflammation and improved survival. Clin Colorectal Cancer. 2015;14:185–191. doi: 10.1016/j.clcc.2015.02.004.
    1. Turner N, et al. Analysis of local chronic inflammatory cell infiltrate combined with systemic inflammation improves prognostication in stage II colon cancer independent of standard clinicopathologic criteria. Int J Cancer. 2016;138:671–678. doi: 10.1002/ijc.29805.
    1. Galon J, et al. Intratumoral immune reaction: a novel paradigm for cancer. J Clin Oncol. 2011;29(4_suppl):471–471. doi: 10.1200/jco.2011.29.4_suppl.471.
    1. Kwon KA, et al. Systemic inflammatory response in predicting survival in patients with operable colorectal cancer. J Clin Oncol. 2011;29(4_suppl):456–456. doi: 10.1200/jco.2011.29.4_suppl.456.
    1. Caronni, N., Savino, B. & Bonecchi R. Myelod cells in cancer-related inflammation. Immunobiology220, 249–53 (2015).
    1. Borsig L, et al. Inflammatory chemokines and metastasis-tracing the accessory. Oncogene. 2014;33:3217–32124. doi: 10.1038/onc.2013.272.
    1. Absenger G, et al. Preoperative Neutrophil-to Lymphocyte Ratio predicts Clinical Outcome in Patients with Stage II and III Colon Cancer. Anticancer Res. 2013;33:4591–4594.
    1. Malietzis G, et al. A preoperative neutrophil to lymphocyte ratio of 3 predicts disease-free survival after curative elective colorectal cancer surgery. Ann Surg. 2013;260:287–292. doi: 10.1097/SLA.0000000000000216.
    1. Ding ER, et al. Elevated preoperative neutrophil to lymphocyte ratio predicts risk of recurrence following curative resection for stage IIA colon cancer. Int J Colorectal Dis. 2010;25:1427–1433. doi: 10.1007/s00384-010-1052-0.
    1. Bensalah K, et al. Prognostic value of thrombocytosis in renal cell carcinoma. J Urol. 2006;175:859–863. doi: 10.1016/S0022-5347(05)00526-4.
    1. Hernandez E, Donohue KA, Anderson LL, Heller PB, Stehman FB. The significance of thrombocytosis in patients with locally advanced cervical carcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2000;78:137–142. doi: 10.1006/gyno.2000.5838.
    1. Gu X, et al. Prognostic value of platelet to lymphocyte ratio in non-small cell lung cancer: evidence from 3,430 patients. Sci Rep. 2016;6:23893. doi: 10.1038/srep23893.
    1. Aoe K, et al. Thrombocytosis as a useful prognostic indicator in patients with lung cancer. Respiration. 2004;71:170–173. doi: 10.1159/000076679.
    1. Adams RA, et al. Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for fist-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet Oncol. 2011;12:642–653. doi: 10.1016/S1470-2045(11)70102-4.
    1. Chiang SF, et al. Can neutrophil-to-lymphocyte ratio predict the survival of colorectal cancer patients who have received curative surgery electively? Int J Colorectal Dis. 2012;27:1347–1357. doi: 10.1007/s00384-012-1459-x.
    1. Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis. 2003;6:283–287. doi: 10.1023/B:.
    1. Lin EY, Pollard JW. Role of infiltrated leucocytes in tumour growth and spread. Br J Cancer. 2010;90:2053–2058. doi: 10.1038/sj.bjc.6601705.
    1. Terzic J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer. Gastroenterology. 2010;138:2101–2114. doi: 10.1053/j.gastro.2010.01.058.
    1. Egan K, et al. Platelet adhesion and degranulation induce pro-suvival and pro-angiogenic signalling in ovarian cancer cells. PLoS One. 2011;6:26125. doi: 10.1371/journal.pone.0026125.
    1. 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;29:132–140. doi: 10.1097/00006676-200408000-00008.
    1. Pedrazzani C, et al. Management of nodal disease from colon cancer in the laparoscopic era. Int J Colorectal Dis. 2015;30:303–314. doi: 10.1007/s00384-014-2075-8.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever