Prognostic impact of the combination of neutrophil-to-lymphocyte ratio and Glasgow prognostic score in colorectal cancer: a retrospective cohort study
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Although neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte count, and Glasgow prognostic score (GPS) are well-known prognostic markers in cancer, their prognostic importance is still controversial. We evaluated the prognostic value of NLR, PLR, monocyte count, and GPS in colorectal cancer (CRC).
We retrospectively evaluated 448 CRC patients undergoing curative resection. We compared overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) between dichotomized groups by the optimal cutoff point. Univariate and multivariate analyses were applied to identify prognostic factors.
High NLR, high monocyte count, and high GPS exhibited significantly worse prognosis in OS, CSS, and DFS compared with low NLR, low monocyte count, and low GPS, respectively. In contrast, PLR was not significantly associated with OS, CSS, and DFS. The univariate and multivariate analyses indicated that poor OS was significantly associated with age ≥ 69 and high NLR; that poor CSS was significantly associated with age ≥ 69, M factor, high CA19-9, adjuvant chemotherapy, and high GPS; and that poor DFS was significantly associated with venous invasion, high NLR, and high GPS. When 448 patients were classified into three groups based on NLR and GPS, there was a significant difference in OS, CSS, and DFS between all the three groups. Patients with NLR ≥ 2.05 and GPS = 1/2 exhibited remarkably poorer prognosis, whereas those with both NLR < 2.05 and GPS = 0 exhibited remarkably better prognosis.
Combination of NLR and GPS can be a novel scoring system to effectively stratify outcome in CRC.
KeywordsSystemic inflammatory response Colorectal cancer Neutrophil-to-lymphocyte ratio Glasgow prognostic score
This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to KK and SI).
KK, SI and YS planned the study concept and design. Acquisition of data was done by SI. Analysis and interpretation of data was done by SI, KK, RO, and HK. KK and SI wrote the manuscript, and edited by all the authors.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 7.Galizia G, Lieto E, Zamboli A, De Vita F, Castellano P, Romano C, Auricchio A, Cardella F, De Stefano L, Orditura M (2015) Neutrophil to lymphocyte ratio is a strong predictor of tumor recurrence in early colon cancers: a propensity score-matched analysis. Surgery 158(1):112–120CrossRefGoogle Scholar
- 8.Patel M, McSorley ST, Park JH, Roxburgh CSD, Edwards J, Horgan PG, McMillan DC (2018) The relationship between right-sided tumour location, tumour microenvironment, systemic inflammation, adjuvant therapy and survival in patients undergoing surgery for colon and rectal cancer. Br J Cancer 118(5):705–712CrossRefGoogle Scholar
- 9.Templeton AJ, McNamara MG, Šeruga B, Vera-Badillo FE, Aneja P, Ocaña A, Leibowitz-Amit R, Sonpavde G, Knox JJ, Tran B, Tannock IF, Amir E (2014) Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst 106(6):dju124CrossRefGoogle Scholar
- 13.Ozawa T, Ishihara S, Nishikawa T, Tanaka T, Tanaka J, Kiyomatsu T, Hata K, Kawai K, Nozawa H, Kazama S, Yamaguchi H, Sunami E, Kitayama J, Watanabe T (2015) The preoperative platelet to lymphocyte ratio is a prognostic marker in patients with stage II colorectal cancer. Int J Color Dis 30(9):1165–1171CrossRefGoogle Scholar
- 22.Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372(26):2509–2520CrossRefGoogle Scholar
- 23.Mizuno R, Kawada K, Itatani Y, Ogawa R, Kiyasu Y, Sakai Y (2019) The role of tumor-associated neutrophils in colorectal cancer. Int J Mol Sci 20(3)Google Scholar
- 24.Itatani Y, Kawada K, Fujishita T, Kakizaki F, Hirai H, Matsumoto T, Iwamoto M, Inamoto S, Hatano E, Hasegawa S, Maekawa T, Uemoto S, Sakai Y, Taketo MM (2013) Loss of SMAD4 from colorectal cancer cells promotes CCL15 expression to recruit CCR1+ myeloid cells and facilitate liver metastasis. Gastroenterology 145(5):1064–1075CrossRefGoogle Scholar
- 25.Inamoto S, Itatani Y, Yamamoto T, Minamiguchi S, Hirai H, Iwamoto M, Hasegawa S, Taketo MM, Sakai Y, Kawada K (2015) Loss of SMAD4 promotes colorectal cancer progression by accumulation of myeloid-derived suppressor cells through CCL15-CCR1 chemokine axis. Clin Cancer Res 22(2):492–501CrossRefGoogle Scholar
- 26.Yamamoto T, Kawada K, Itatani Y, Inamoto S, Okamura R, Iwamoto M, Miyamoto E, Chen-Yoshikawa TF, Hirai H, Hasegawa S, Date H, Taketo MM, Sakai Y (2017) Loss of SMAD4 promotes lung metastasis of colorectal cancer by accumulation of CCR1+ tumor-associated neutrophils through CCL15-CCR1 axis. Clin Cancer Res 23(3):833–844CrossRefGoogle Scholar
- 27.Ogawa R, Yamamoto T, Hirai H, Hanada K, Kiyasu Y, Nishikawa G, Mizuno R, Inamoto S, Itatani Y, Sakai Y, Kawada K (2019) Loss of SMAD4 promotes colorectal cancer progression by recruiting tumor-associated neutrophils via CXCL1/8-CXCR2 axis. Clin Cancer Res:2887–2899. https://doi.org/10.1158/1078-0432.CCR-18-3684
- 28.Pagès F, Mlecnik B, Marliot F, Bindea G, Ou FS, Bifulco C, Lugli A, Zlobec I, Rau TT, Berger MD, Nagtegaal ID, Vink-Börger E, Hartmann A, Geppert C, Kolwelter J, Merkel S, Grützmann R, Van den Eynde M, Jouret-Mourin A, Kartheuser A, Léonard D, Remue C, Wang JY, Bavi P, Roehrl MHA, Ohashi PS, Nguyen LT, Han S, MacGregor HL, Hafezi-Bakhtiari S, Wouters BG, Masucci GV, Andersson EK, Zavadova E, Vocka M, Spacek J, Petruzelka L, Konopasek B, Dundr P, Skalova H, Nemejcova K, Botti G, Tatangelo F, Delrio P, Ciliberto G, Maio M, Laghi L, Grizzi F, Fredriksen T, Buttard B, Angelova M, Vasaturo A, Maby P, Church SE, Angell HK, Lafontaine L, Bruni D, El Sissy C, Haicheur N, Kirilovsky A, Berger A, Lagorce C, Meyers JP, Paustian C, Feng Z, Ballesteros-Merino C, Dijkstra J, van de Water C, van Lent-van Vliet S, Knijn N, Mușină AM, Scripcariu DV, Popivanova B, Xu M, Fujita T, Hazama S, Suzuki N, Nagano H, Okuno K, Torigoe T, Sato N, Furuhata T, Takemasa I, Itoh K, Patel PS, Vora HH, Shah B, Patel JB, Rajvik KN, Pandya SJ, Shukla SN, Wang Y, Zhang G, Kawakami Y, Marincola FM, Ascierto PA, Sargent DJ, Fox BA, Galon J (2018) International validation of the consensus immunoscore for the classification of colon cancer: a prognostic and accuracy study. Lancet 391(10135):2128–2139CrossRefGoogle Scholar
- 29.Ogino S, Nosho K, Irahara N, Meyerhardt JA, Baba Y, Shima K, Glickman JN, Ferrone CR, Mino-Kenudson M, Tanaka N, Dranoff G, Giovannucci EL, Fuchs CS (2009) 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 15(20):6412–6420CrossRefGoogle Scholar
- 35.Mano Y, Shirabe K, Yamashita Y, Harimoto N, Tsujita E, Takeishi K, Aishima S, Ikegami T, Yoshizumi T, Yamanaka T, Maehara Y (2013) Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. Ann Surg 258(2):301–305CrossRefGoogle Scholar