Open Access

Neutrophil-to-lymphocyte ratio predicts overall survival of patients with combined hepatocellular cholangiocarcinoma

  • Authors:
    • Chaobin He
    • Yize Mao
    • Xiangming Lao
    • Shengping Li
    • Xiaojun Lin
  • View Affiliations

  • Published online on: January 26, 2018     https://doi.org/10.3892/ol.2018.7882
  • Pages: 4262-4268
  • Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

The neutrophil-to-lymphocyte ratio (NLR) has been regarded as a prognostic factor in various types of cancer. The present study aimed to identify the association between NLR and combined hepatocellular cholangiocarcinoma (cHCC‑CC) in patients who underwent surgical resection. The present study retrospectively reviewed 59 patients who were diagnosed with cHCC‑CC and treated with surgical resection between January 2000 and October 2014 at the Department of Hepatobiliary and Pancreatic Surgery at Sun Yat‑sen University Cancer Center (Guangzhou, China). The patients were divided into two groups: NLR≤2.75 and NLR>2.75. Patients with stage I and II or stage III and IV disease were classified into early‑ and advanced‑stage groups, respectively, according to the Tumor‑Node‑Metastasis (TNM) staging system. Overall survival time (OS) was estimated using the Kaplan‑Meier method. Univariate and multivariate Cox regression models were used to evaluate the prognostic value of NLR. The NLR value was significantly higher in the HCC advanced‑stage group compared with that in the HCC early‑stage group according to the TNM staging system (3.19 vs. 2.00; P=0.001). The median survival time was 83.6 months in the NLR≤2.75 group and 15 months in the NLR>2.75 group (P=0.004). Upon multivariate analysis, NLR>2.75 was an independent prognostic factor for poor cHCC‑CC outcomes. Overall, the easily evaluated pre‑treatment NLR may be an independent prognostic factor for patients with cHCC-CC treated by surgical resection.

References

1 

Allen RA and Lisa JR: Combined liver cell and bile duct carcinoma. Am J Pathol. 25:647–655. 1949.PubMed/NCBI

2 

Jarnagin WR, Weber S, Tickoo SK, Koea JB, Obiekwe S, Fong Y, DeMatteo RP, Blumgart LH and Klimstra D: Combined hepatocellular and cholangiocarcinoma: Demographic, clinical, and prognostic factors. Cancer. 94:2040–2046. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Panjala C, Senecal DL, Bridges MD, Kim GP, Nakhleh RE, Nguyen JH and Harnois DM: The diagnostic conundrum and liver transplantation outcome for combined hepatocellular-cholangiocarcinoma. Am J Transplant. 10:1263–1267. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Bosman FT, Carneiro F, Hruban RH and Theise ND: WHO classification of tumours of the digestive system. 4th. International Agency for Research on Cancer Publisher, Lyon. World Health Organization; 2010

5 

Kim SH, Park YN, Lim JH, Choi GH, Choi JS and Kim KS: Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma. Eur J Surg Oncol. 40:976–981. 2014. View Article : Google Scholar : PubMed/NCBI

6 

Chu KJ, Lu CD, Dong H, Fu XH, Zhang HW and Yao XP: Hepatitis B virus-related combined hepatocellular-cholangiocarcinoma: Clinicopathological and prognostic analysis of 390 cases. Eur J Gastroenterol Hepatol. 26:192–199. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Zheng W, Yao M, Sai W, Qian Q, Pan L, Qiu L, Huang J, Wu W and Yao D: Diagnostic and prognostic significance of secretory clusterin expression in patients with hepatocellular carcinoma. Tumour Biol. 37:999–1008. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Kassahun WT and Hauss J: Management of combined hepatocellular and cholangiocarcinoma. Int J Clin Pract. 62:1271–1278. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Zahorec R: Ratio of neutrophil to lymphocyte counts-rapid and simple parameter of systemic inflammation and stress in critically ill. Bratisl Lek Listy. 102:5–14. 2001.(In English, Slovak). PubMed/NCBI

11 

Sarraf KM, Belcher E, Raevsky E, Nicholson AG, Goldstraw P and Lim E: Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer. J Thorac Cardiovasc Surg. 137:425–428. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Yamanaka T, Matsumoto S, Teramukai S, Ishiwata R, Nagai Y and Fukushima M: The baseline ratio of neutrophils to lymphocytes is associated with patient prognosis in advanced gastric cancer. Oncology. 73:215–220. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Cho H, Hur HW, Kim SW, Kim SH, Kim JH, Kim YT and Lee K: Pre-treatment neutrophil to lymphocyte ratio is elevated in epithelial ovarian cancer and predicts survival after treatment. Cancer Immunol Immunother. 58:15–23. 2009. View Article : Google Scholar : PubMed/NCBI

14 

An X, Ding PR, Li YH, Wang FH, Shi YX, Wang ZQ, He YJ, Xu RH and Jiang WQ: Elevated neutrophil to lymphocyte ratio predicts survival in advanced pancreatic cancer. Biomarkers. 15:516–522. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Gomez D, Farid S, Malik HZ, Young AL, Toogood GJ, Lodge JP and Prasad KR: Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after curative resection for hepatocellular carcinoma. World J Surg. 32:1757–1762. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Kayadibi H, Sertoglu E, Uyanik M and Tapan S: Neutrophil-lymphocyte ratio is useful for the prognosis of patients with hepatocellular carcinoma. World J Gastroenterol. 20:9631–9632. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Oh BS, Jang JW, Kwon JH, You CR, Chung KW, Kay CS, Jung HS and Lee S: Prognostic value of C-reactive protein and neutrophil-to-lymphocyte ratio in patients with hepatocellular carcinoma. BMC Cancer. 13:782013. View Article : Google Scholar : PubMed/NCBI

18 

Xiao WK, Chen D, Li SQ, Fu SJ, Peng BG and Liang LJ: Prognostic significance of neutrophil-lymphocyte ratio in hepatocellular carcinoma: A meta-analysis. BMC Cancer. 14:1172014. View Article : Google Scholar : PubMed/NCBI

19 

Shen SL, Fu SJ, Huang XQ, Chen B, Kuang M, Li SQ, Hua YP, Liang LJ and Peng BG: Elevated preoperative peripheral blood monocyte count predicts poor prognosis for hepatocellular carcinoma after curative resection. BMC Cancer. 14:7442014. View Article : Google Scholar : PubMed/NCBI

20 

Chen Q, Yang LX, Li XD, Yin D, Shi SM, Chen EB, Yu L, Zhou ZJ, Zhou SL, Shi YH, et al: The elevated preoperative neutrophil-to-lymphocyte ratio predicts poor prognosis in intrahepatic cholangiocarcinoma patients undergoing hepatectomy. Tumour Biol. 36:5283–5289. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Edge S, Byrd D, Compton C, Fritz A, Greene F and Trotti A: AJCC cancer staging manual. 7. American Joint Committee on Cancer; 2010

22 

Heagerty PJ, Lumley T and Pepe MS: Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 56:337–344. 2000. View Article : Google Scholar : PubMed/NCBI

23 

Jaiswal M, LaRusso NF, Burgart LJ and Gores GJ: Inflammatory cytokines induce DNA damage and inhibit DNA repair in cholangiocarcinoma cells by a nitric oxide-dependent mechanism. Cancer Res. 60:184–190. 2000.PubMed/NCBI

24 

de Visser KE, Eichten A and Coussens LM: Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 6:24–37. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Jackson JR, Seed MP, Kircher CH, Willoughby DA and Winkler JD: The codependence of angiogenesis and chronic inflammation. FASEB J. 11:457–465. 1997. View Article : Google Scholar : PubMed/NCBI

26 

Ishigami S, Natsugoe S, Tokuda K, Nakajo A, Che X, Iwashige H, Aridome K, Hokita S and Aikou T: Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer. 88:577–583. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Liu CH, Chang SH, Narko K, Trifan OC, Wu MT, Smith E, Haudenschild C, Lane TF and Hla T: Overexpression of cyclooxygenase-2 is sufficient to induce tumorigenesis in transgenic mice. J Biol Chem. 276:18563–18569. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Schoppmann SF, Birner P, Stöckl J, Kalt R, Ullrich R, Caucig C, Kriehuber E, Nagy K, Alitalo K and Kerjaschki D: Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol. 161:947–956. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Dannenberg AJ and Subbaramaiah K: Targeting cyclooxygenase-2 in human neoplasia: Rationale and promise. Cancer Cell. 4:431–436. 2003. View Article : Google Scholar : PubMed/NCBI

30 

Mantovani A, Allavena P, Sica A and Balkwill F: Cancer-related inflammation. Nature. 454:436–444. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Zou W: Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer. 5:263–274. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Perez DR, Baser RE, Cavnar MJ, Balachandran VP, Antonescu CR, Tap WD, Strong VE, Brennan MF, Coit DG, Singer S and Dematteo RP: Blood neutrophil-to-lymphocyte ratio is prognostic in gastrointestinal stromal tumor. Ann Surg Oncol. 20:593–599. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Williams KA, Labidi-Galy SI, Terry KL, Vitonis AF, Welch WR, Goodman A and Cramer DW: Prognostic significance and predictors of the neutrophil-to-lymphocyte ratio in ovarian cancer. Gynecol Oncol. 132:542–550. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Cai X, Zhai J, Kaplan DE, Zhang Y, Zhou L, Chen X, Qian G, Zhao Q, Li Y, Gao L, et al: Background progenitor activation is associated with recurrence after hepatectomy of combined hepatocellular-cholangiocarcinoma. Hepatology. 56:1804–1816. 2012. View Article : Google Scholar : PubMed/NCBI

35 

Zeng X and Tao H: Diagnostic and prognostic serum marker of cholangiocarcinoma (Review). Oncol Lett. 9:3–8. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

April 2018
Volume 15 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
He, C., Mao, Y., Lao, X., Li, S., & Lin, X. (2018). Neutrophil-to-lymphocyte ratio predicts overall survival of patients with combined hepatocellular cholangiocarcinoma. Oncology Letters, 15, 4262-4268. https://doi.org/10.3892/ol.2018.7882
MLA
He, C., Mao, Y., Lao, X., Li, S., Lin, X."Neutrophil-to-lymphocyte ratio predicts overall survival of patients with combined hepatocellular cholangiocarcinoma". Oncology Letters 15.4 (2018): 4262-4268.
Chicago
He, C., Mao, Y., Lao, X., Li, S., Lin, X."Neutrophil-to-lymphocyte ratio predicts overall survival of patients with combined hepatocellular cholangiocarcinoma". Oncology Letters 15, no. 4 (2018): 4262-4268. https://doi.org/10.3892/ol.2018.7882