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

He,Chaobin; Mao,Yize; Lao,Xiangming; Li,Shengping; Lin,Xiaojun

doi:10.3892/ol.2018.7882

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

Affiliations: Department of Hepatobiliary Oncology, Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China
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: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View 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