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Hematologic Markers of Lung Metastasis in Stage IV Colorectal Cancer

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Abstract

Background

Many studies showed an association between absolute neutrophil count (ANC), absolute monocyte count (AMC), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) with poor overall survival (OS) in patients with cancer. However, only a few studies were conducted to further investigate this association in colorectal cancer (CRC).

Methods

Clinical data from 299 stage IV CRC patients treated at King Hussein Cancer Center from 2004 to 2012 have been retrospectively reviewed. We examined the association between ANC, AMC, MLR, PLR, and NLR with lung metastasis in stage IV CRC. Receiver Operating Characteristic (ROC) curve analysis was operated to determine the optimal NLR cutoff value. Univariate and multivariate analysis were performed.

Results

The ROC value of 3.4 was determined as the cutoff value of NLR to study the association. Univariate and multivariate analysis showed that patients with high baseline NLR (≥ 3.4) had more baseline lung metastasis than patients with low NLR (< 3.4) (p = 0.0001, p = 0.0151, respectively). Also, baseline NLR correlated significantly with the presence of lymphovascular invasion (p = 0.001). In patients with no baseline lung metastasis, high post-treatment NLR was associated with consequent development of lung metastasis (p = 0.0227). Other markers including ANC, AMC, MLR, and PLR were significantly associated with lung metastasis at time of diagnosis (p = 0.0006, p = 0.0006, p = 0.0187, and p = 0.001, respectively).

Conclusion

Results are suggesting that different hematologic markers obtained from a cheap test (CBC) could potentially be used to predict the likelihood of lung metastasis in stage IV CRC. Prospective studies are needed to further assess the immune cells’ role in tumor metastasis promotion.

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References

  1. Haggar FA, Boushey RP. Colorectal cancer epidemiology: incidence, mortality, survival, and risk factors. Clin Colon Rectal Surg. 2009;22(4):191–7. https://doi.org/10.1055/s-0029-1242458. PubMed PMID: 21037809; PubMed Central PMCID: PMCPMC2796096.

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016;66(1):7–30. Epub 2016/01/07. https://doi.org/10.3322/caac.21332. PubMed.

  3. Moore MM, Chua W, Charles KA, Clarke SJ. Inflammation and cancer: causes and consequences. Clin Pharmacol Ther 2010;87(4):504–508. Epub 2010/02/10. https://doi.org/10.1038/clpt.2009.254. PubMed.

  4. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99. https://doi.org/10.1016/j.cell.2010.01.025. PubMed PMID: 20303878; PubMed Central PMCID: PMCPMC2866629.

  5. Tan D, Fu Y, Su Q, Wang H. Prognostic role of platelet-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Medicine (Baltimore). 2016;95(24):e3837. https://doi.org/10.1097/MD.0000000000003837. PubMed PMID: 27310960; PubMed Central PMCID: PMCPMC4998446.

  6. Nagasaki T, Akiyoshi T, Fujimoto Y, Konishi T, Nagayama S, Fukunaga Y, Ueno M Prognostic impact of neutrophil-to-lymphocyte ratio in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy. Dig Surg 2015;32(6):496–503. Epub 2015/11/07. https://doi.org/10.1159/000441396. PubMed.

  7. Li MX, Liu XM, Zhang XF, Zhang JF, Wang WL, Zhu Y, Dong J, Cheng JW, Liu ZW, Ma L, Lv Y Prognostic role of neutrophil-to-lymphocyte ratio in colorectal cancer: a systematic review and meta-analysis. Int J Cancer 2014;134(10):2403–2413. Epub 2014/01/29. https://doi.org/10.1002/ijc.28536. PubMed.

  8. An X, Ding PR, Wang FH, Jiang WQ, Li YH. Elevated neutrophil to lymphocyte ratio predicts poor prognosis in nasopharyngeal carcinoma. Tumour Biol 2011;32(2):317–324. Epub 2010/10/30. https://doi.org/10.1007/s13277-010-0124-7. PubMed.

  9. An X, Ding PR, Li YH, Wang FH, Shi YX, Wang ZQ, He YJ, Xu RH, Jiang WQ Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer. Biomarkers 2010;15(6):516–522. https://doi.org/10.3109/1354750X.2010.491557. PubMed.

  10. Liu H, Liu G, Bao Q, Sun W, Bao H, Bi L, Wen W, Liu Y, Wang Z, Yin X, Bai Y, Hu X The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in rectal carcinoma. J Gastrointest Cancer 2010;41(2):116–120. https://doi.org/10.1007/s12029-009-9125-4. PubMed.

  11. Gondo T, Nakashima J, Ohno Y, Choichiro O, Horiguchi Y, Namiki K, Yoshioka K, Ohori M, Hatano T, Tachibana M Prognostic value of neutrophil-to-lymphocyte ratio and establishment of novel preoperative risk stratification model in bladder cancer patients treated with radical cystectomy. Urology 2012;79(5):1085–1091. Epub 2012/03/23. https://doi.org/10.1016/j.urology.2011.11.070. PubMed.

  12. Stotz M, Gerger A, Eisner F, Szkandera J, Loibner H, Ress AL, et al. Increased neutrophil-lymphocyte ratio is a poor prognostic factor in patients with primary operable and inoperable pancreatic cancer. Br J Cancer. 2013;109(2):416–21. Epub 2013/06/25. https://doi.org/10.1038/bjc.2013.332. PubMed PMID: 23799847; PubMed Central PMCID: PMCPMC3721392.

  13. Paramanathan A, Saxena A, Morris DL. A systematic review and meta-analysis on the impact of pre-operative neutrophil lymphocyte ratio on long term outcomes after curative intent resection of solid tumours. Surg Oncol 2014;23(1):31–39. Epub 2013/12/20. https://doi.org/10.1016/j.suronc.2013.12.001. PubMed.

  14. Szkandera J, Absenger G, Liegl-Atzwanger B, Pichler M, Stotz M, Samonigg H, et al. Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients. Br J Cancer. 2013;108(8):1677–83. Epub 2013/04/04. https://doi.org/10.1038/bjc.2013.135. PubMed PMID: 23558897; PubMed Central PMCID: PMCPMC3668478.

  15. Ying HQ, Deng QW, He BS, Pan YQ, Wang F, Sun HL, Chen J, Liu X, Wang SK The prognostic value of preoperative NLR, d-NLR, PLR and LMR for predicting clinical outcome in surgical colorectal cancer patients. Med Oncol 2014;31(12):305. Epub 2014/10/30. https://doi.org/10.1007/s12032-014-0305-0. PubMed.

  16. Koh YW, Choi JH, Ahn MS, Choi YW, Lee HW. Baseline neutrophil-lymphocyte ratio is associated with baseline and subsequent presence of brain metastases in advanced non-small-cell lung cancer. Sci Rep. 2016;6:38585. Epub 2016/12/07. https://doi.org/10.1038/srep38585. PubMed PMID: 27924837; PubMed Central PMCID: PMCPMC5141478.

  17. Riihimäki M, Thomsen H, Sundquist K, Hemminki K. Colorectal cancer patients: what do they die of? Frontline Gastroenterol. 2012;3(3):143–9. Epub 2012/04/27. https://doi.org/10.1136/flgastro-2012-100141. PubMed PMID: 28839655; PubMed Central PMCID: PMCPMC5517285.

  18. van der Geest LG, Lam-Boer J, Koopman M, Verhoef C, Elferink MA, de Wilt JH. Nationwide trends in incidence, treatment and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis 2015;32(5):457–465. Epub 2015/04/22. https://doi.org/10.1007/s10585-015-9719-0. PubMed.

  19. Noone AM, Cronin KA, Altekruse SF, Howlader N, Lewis DR, Petkov VI, et al. Cancer incidence and survival trends by subtype using data from the Surveillance Epidemiology and End Results Program, 1992–2013. Cancer Epidemiol Biomarkers Prev. 2017;26(4):632–41. Epub 2016/12/12. https://doi.org/10.1158/1055-9965.EPI-16-0520. PubMed PMID: 27956436; PubMed Central PMCID: PMCPMC5380602.

  20. Balkwill F, Mantovani A. Inflammation and cancer: back to Virchow? Lancet 2001;357(9255):539–545. https://doi.org/10.1016/S0140-6736(00)04046-0. PubMed.

  21. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature 2008;454(7203):436–444. https://doi.org/10.1038/nature07205. PubMed.

  22. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7. https://doi.org/10.1038/nature01322. PubMed PMID: 12490959; PubMed Central PMCID: PMCPMC2803035.

  23. Kitamura T, Qian BZ, Pollard JW. Immune cell promotion of metastasis. Nat Rev Immunol. 2015;15(2):73–86. https://doi.org/10.1038/nri3789. PubMed PMID: 25614318; PubMed Central PMCID: PMCPMC4470277.

  24. 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(4):283–287. https://doi.org/10.1023/B:AGEN.0000029415.62384.ba. PubMed.

  25. Qian BZ, Pollard JW. Macrophage diversity enhances tumor progression and metastasis. Cell. 2010;141(1):39–51. https://doi.org/10.1016/j.cell.2010.03.014. PubMed PMID: 20371344; PubMed Central PMCID: PMCPMC4994190.

  26. Dirkx AE, Oude Egbrink MG, Wagstaff J, Griffioen AW. Monocyte/macrophage infiltration in tumors: modulators of angiogenesis. J Leukoc Biol 2006;80(6):1183–1196. Epub 2006/09/22. https://doi.org/10.1189/jlb.0905495. PubMed.

  27. Yuan A, Chen JJ, Yang PC. Pathophysiology of tumor-associated macrophages. Adv Clin Chem 2008;45:199–223. PubMed.

  28. Kitayama J, Yasuda K, Kawai K, Sunami E, Nagawa H. Circulating lymphocyte is an important determinant of the effectiveness of preoperative radiotherapy in advanced rectal cancer. BMC Cancer. 2011;11:64. Epub 2011/02/10. https://doi.org/10.1186/1471-2407-11-64. PubMed PMID: 21306650; PubMed Central PMCID: PMCPMC3041780.

  29. Mahmoud SM, Paish EC, Powe DG, Macmillan RD, Grainge MJ, Lee AH, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 2011;29(15):1949–1955. Epub 2011/04/11. https://doi.org/10.1200/JCO.2010.30.5037. PubMed.

  30. Clemente CG, Mihm MC, Bufalino R, Zurrida S, Collini P, Cascinelli N. Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 1996;77(7):1303–1310. https://doi.org/10.1002/(SICI)1097-0142(19960401)77:7<1303::AID-CNCR12>3.0.CO;2-5. PubMed.

  31. Ogino S, Nosho K, Irahara N, Meyerhardt JA, Baba Y, Shima K, et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype. Clin Cancer Res. 2009;15(20):6412–20. Epub 2009/10/13. https://doi.org/10.1158/1078-0432.CCR-09-1438. PubMed PMID: 19825961; PubMed Central PMCID: PMCPMC2771425.

  32. Templeton AJ, Knox JJ, Lin X, Simantov R, Xie W, Lawrence N, Broom R, Fay AP, Rini B, Donskov F, Bjarnason GA, Smoragiewicz M, Kollmannsberger C, Kanesvaran R, Alimohamed N, Hermanns T, Wells JC, Amir E, Choueiri TK, Heng DYC Change in neutrophil-to-lymphocyte ratio in response to targeted therapy for metastatic renal cell carcinoma as a prognosticator and biomarker of efficacy. Eur Urol 2016;70(2):358–364. Epub 2016/02/28. https://doi.org/10.1016/j.eururo.2016.02.033. PubMed.

  33. Ohno Y, Nakashima J, Ohori M, Gondo T, Hatano T, Tachibana M. Followup of neutrophil-to-lymphocyte ratio and recurrence of clear cell renal cell carcinoma. J Urol 2012;187(2):411–417. Epub 2011/12/15. doi: https://doi.org/10.1016/j.juro.2011.10.026. PubMed.

  34. Riihimäki M, Hemminki A, Sundquist J, Hemminki K. Patterns of metastasis in colon and rectal cancer. Sci Rep. 2016;6:29765. Epub 2016/07/15. doi: https://doi.org/10.1038/srep29765. PubMed PMID: 27416752; PubMed Central PMCID: PMCPMC4945942.

  35. Shoenfeld Y, Gurewich Y, Gallant LA, Pinkhas J. Prednisone-induced leukocytosis. Influence of dosage, method and duration of administration on the degree of leukocytosis. Am J Med 1981;71(5):773–778. PubMed.

  36. Nakagawa M, Terashima T, D’yachkova Y, Bondy GP, Hogg JC, van Eeden SF. Glucocorticoid-induced granulocytosis: contribution of marrow release and demargination of intravascular granulocytes. Circulation 1998;98(21):2307–2313. PubMed.

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Acknowledgements

We would like to thank Mrs. Dalia Al-Rimawi and Ayat Taqash from the Biostatistics Unit at the Office of Scientific Affairs and Research for their help with the statistical analysis.

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Authors and Affiliations

  1. Clinical Research Office, King Hussein Cancer Center, Amman, Jordan

    Mohammad Abu-Shawer

  2. University of Jordan School of Medicine, Amman, Jordan

    Osama Abu-Shawer, Mamoun Souleiman, Mohammad Akkawi, Osama Alshakhatreh & Tamer Altamimi

  3. Office of Scientific Affairs and Research, King Hussein Cancer Center, Amman, Jordan

    Amal Al-Omari

  4. Department of Pathology and Laboratory Medicine, King Hussein Cancer Center, Amman, 11941, Jordan

    Maysa Al-Hussaini

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  1. Mohammad Abu-Shawer
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Abu-Shawer, M., Abu-Shawer, O., Souleiman, M. et al. Hematologic Markers of Lung Metastasis in Stage IV Colorectal Cancer. J Gastrointest Canc 50, 428–433 (2019). https://doi.org/10.1007/s12029-018-0089-0

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