Preoperative neutrophil-to-lymphocyte ratio predicts recurrence of patients with single-nodule small hepatocellular carcinoma following curative resection: a retrospective report

World Journal of Surgical Oncology

Cheng-You Du²  Ping Huang²  Shi-Qiao Luo²  De-Wei Li²  Zhuo-Wei Tang¹  Rui Liao² 

[1] Department of General Surgery, Mianyang Central Hospital, Mianyang 621000, China;Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

关键词: Prognosis;    Lymphocyte;    Neutrophil;    Inflammation;    Liver cancer;   

Others  :  1223955
DOI  :  10.1186/s12957-015-0670-y

 received in 2015-05-29, accepted in 2015-08-03,  发布年份 2015

【 摘 要 】

Background

Preoperative neutrophil-to-lymphocyte ratio (NLR) has been identified as a predictor for the recurrence of hepatocellular carcinoma (HCC), but the cut-off of NLR is inconsistent in various studies. Thus, we detected the prognostic value of preoperative NLR in the single-nodule small HCC (SHCC) patients using X-tile for cutpoint.

Methods

Between January 2007 and December 2010, a total of 222 single-nodule SHCC patients underwent curative resection and were examined for the prognostic roles of preoperative NLR by X-tile.

Results

In this study, all patients were divided into the low-NLR subgroup (NLR ≤ 2.1) and the high-NLR subgroup (NLR > 2.1) by X-tile. Preoperative NLR showed predictive value for time to recurrence (TTR) and overall survival (OS). Moreover, NLR was associated with total bilirubin, white blood cell counts, and HBsAg, respectively (P = 0.012, <0.001, and 0.011, respectively). Especially, NLR could discriminate the outcome of patients in the subgroup with alpha-fetoprotein (AFP) levels of ≤400 ng/mL. Importantly, postoperative transcatheter arterial chemoembolization (TACE) had close relationship with OS (P = 0.001) and TTR (P ≤ 0.001).

Conclusions

Therefore, this study indicates that preoperative NLR, divided by X-tile for the cutpoint, is a simple prognostic marker for the patients with single-nodule SHCC after curative resection.

【 授权许可】

   
2015 Liao et al.

【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

【 参考文献 】

• [1]Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140:883-899.
• [2]Hernandez-Gea V, Toffanin S, Friedman SL, Llovet JM. Role of the microenvironment in the pathogenesis and treatment of hepatocellular carcinoma. Gastroenterology. 2013; 144:512-527.
• [3]Yang G, Wang Y, Zeng Y, Gao GF, Liang X, Zhou M et al.. Rapid health transition in China, 1990–2010: findings from the Global Burden of Disease Study 2010. Lancet. 2013; 381:1987-2015.
• [4]Poon RT. Prevention of recurrence after resection of hepatocellular carcinoma: a daunting challenge. Hepatology. 2011; 54:757-759.
• [5]Maluccio M, Covey A. Recent progress in understanding, diagnosing, and treating hepatocellular carcinoma. CA Cancer J Clin. 2012; 62:394-399.
• [6]Liao R, Sun TW, Yi Y, Wu H, Li YW, Wang JX et al.. Expression of TREM-1 in hepatic stellate cells and prognostic value in hepatitis B-related hepatocellular carcinoma. Cancer Sci. 2012; 103:984-992.
• [7]Liao R, Sun J, Wu H, Yi Y, Wang JX, He HW et al.. High expression of IL-17 and IL-17RE associate with poor prognosis of hepatocellular carcinoma. J Exp Clin Cancer Res. 2013; 32:3. BioMed Central Full Text
• [8]Liao R, Wu H, Yi Y, Wang JX, Cai XY, He HW et al.. Clinical significance and gene expression study of human hepatic stellate cells in HBV related-hepatocellular carcinoma. J Exp Clin Cancer Res. 2013; 32:22. BioMed Central Full Text
• [9]Xu YF, Yi Y, Qiu SJ, Gao Q, Li YW, Dai CX et al.. PEBP1 downregulation is associated to poor prognosis in HCC related to hepatitis B infection. J Hepatol. 2010; 53:872-879.
• [10]Wang H, Li H, Zhang Y, Wei Q, Ma H, Wu D et al.. Label-free immunosensor based on Pd nanoplates for amperometric immunoassay of alpha-fetoprotein. Biosens Bioelectron. 2014; 53:305-309.
• [11]Budhu A, Forgues M, Ye QH, Jia HL, He P, Zanetti KA et al.. Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment. Cancer Cell. 2006; 10:99-111.
• [12]Sherman M. Recurrence of hepatocellular carcinoma. N Engl J Med. 2008; 359:2045-2047.
• [13]Chen L, Zhang Q, Chang W, Du Y, Zhang H, Cao G. Viral and host inflammation-related factors that can predict the prognosis of hepatocellular carcinoma. Eur J Cancer. 2012; 48:1977-1987.
• [14]Barash H, Gross RE, Edrei Y, Ella E, Israel A, Cohen I, Corchia N, Ben-Moshe T, Pappo O, Pikarsky E, Goldenberg D, Shiloh Y, Galun E, Abramovitch R et al.. Accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks. Proc Natl Acad Sci U S A. 2010; 107:2207-2212.
• [15]Yamamura K, Sugimoto H, Kanda M, Yamada S, Nomoto S, Nakayama G et al.. Comparison of inflammation-based prognostic scores as predictors of tumor recurrence in patients with hepatocellular carcinoma after curative resection. J Hepatobiliary Pancreat Sci. 2014; 21:682-688.
• [16]Schreiber H, Rowley DA. Cancer. Awakening immunity. Science. 2010; 330:761-762.
• [17]Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis. 2009; 30:1073-1081.
• [18]Hoffmann A, Xia Y, Verma IM. Inflammatory tales of liver cancer. Cancer Cell. 2007; 11:99-101.
• [19]Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011; 144:646-674.
• [20]Li YW, Qiu SJ, Fan J, Zhou J, Gao Q, Xiao YS et al.. Intratumoral neutrophils: a poor prognostic factor for hepatocellular carcinoma following resection. J Hepatol. 2011; 54:497-505.
• [21]Li YW, Qiu SJ, Fan J, Gao Q, Zhou J, Xiao YS et al.. Tumor-infiltrating macrophages can predict favorable prognosis in hepatocellular carcinoma after resection. J Cancer Res Clin Oncol. 2009; 135:439-449.
• [22]Gao Q, Qiu SJ, Fan J, Zhou J, Wang XY, Xiao YS et al.. Intratumoral balance of regulatory and cytotoxic T cells is associated with prognosis of hepatocellular carcinoma after resection. J Clin Oncol. 2007; 25:2586-2593.
• [23]Walsh SR, Cook EJ, Goulder F, Justin TA, Keeling NJ. Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer. J Surg Oncol. 2005; 91:181-184.
• [24]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; 109:416-421.
• [25]Ishizuka M, Oyama Y, Abe A, Kubota K. Combination of platelet count and neutrophil to lymphocyte ratio is a useful predictor of postoperative survival in patients undergoing surgery for gastric cancer. J Surg Oncol. 2014; 110:935-941.
• [26]Mano Y, Shirabe K, Yamashita Y, Harimoto N, Tsujita E, Takeishi K et al.. Preoperative neutrophil-to-lymphocyte ratio is a predictor of survival after hepatectomy for hepatocellular carcinoma: a retrospective analysis. Ann Surg. 2013; 258:301-305.
• [27]Liao W, Zhang J, Zhu Q, Qin L, Yao W, Lei B et al.. Preoperative neutrophil-to-lymphocyte ratio as a new prognostic marker in hepatocellular carcinoma after curative resection. Transl Oncol. 2014; 7:248-255.
• [28]Motomura T, Shirabe K, Mano Y, Muto J, Toshima T, Umemoto Y et al.. Neutrophil-lymphocyte ratio reflects hepatocellular carcinoma recurrence after liver transplantation via inflammatory microenvironment. J Hepatol. 2013; 58:58-64.
• [29]Huang ZL, Luo J, Chen MS, Li JQ, Shi M. Blood neutrophil-to-lymphocyte ratio predicts survival in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization. J Vasc Interv Radiol. 2011; 22:702-709.
• [30]Chen TM, Lin CC, Huang PT, Wen CF. Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation. J Gastroenterol Hepatol. 2012; 27:553-561.
• [31]Halazun KJ, Hardy MA, Rana AA, Woodland DC, Luyten EJ, Mahadev S et al.. Negative impact of neutrophil-lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma. Ann Surg. 2009; 250:141-151.
• [32]Dan J, Zhang Y, Peng Z, Huang J, Gao H, Xu L et al.. Postoperative neutrophil-to-lymphocyte ratio change predicts survival of patients with small hepatocellular carcinoma undergoing radiofrequency ablation. PLoS One. 2013; 8: Article ID e58184
• [33]Altman DG, Lausen B, Sauerbrei W, Schumacher M. Dangers of using “optimal” cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst. 1994; 86:829-835.
• [34]Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C et al.. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006; 313:1960-1964.
• [35]Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX et al.. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008; 100:698-711.
• [36]Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004; 10:7252-7259.
• [37]Imai Y, Kubota Y, Yamamoto S, Tsuji K, Shimatani M, Shibatani N et al.. Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells: an in vitro study. J Gastroenterol Hepatol. 2005; 20:287-293.
• [38]McDonald B, Spicer J, Giannais B, Fallavollita L, Brodt P, Ferri LE. Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms. Int J Cancer. 2009; 125:1298-1305.
• [39]Nozawa H, Chiu C, Hanahan D. Infiltrating neutrophils mediate the initial angiogenic switch in a mouse model of multistage carcinogenesis. Proc Natl Acad Sci U S A. 2006; 103:12493-12498.
• [40]Yi Y, He HW, Wang JX, Cai XY, Li YW, Zhou J et al.. The functional impairment of HCC-infiltrating gammadelta T cells, partially mediated by regulatory T cells in a TGFbeta- and IL-10-dependent manner. J Hepatol. 2013; 58:977-983.
• [41]Ding PR, An X, Zhang RX, Fang YJ, Li LR, Chen G 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.
• [42]Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L et al.. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009; 16:183-194.
• [43]Zhou J, Yu L, Gao X, Hu J, Wang J, Dai Z et al.. Plasma microRNA panel to diagnose hepatitis B virus-related hepatocellular carcinoma. J Clin Oncol. 2011; 29:4781-4788.
• [44]Ma WJ, Wang HY, Teng LS. Correlation analysis of preoperative serum alpha-fetoprotein (AFP) level and prognosis of hepatocellular carcinoma (HCC) after hepatectomy. World J Surg Oncol. 2013; 11:212. BioMed Central Full Text
• [45]Sun YF, Xu Y, Yang XR, Guo W, Zhang X, Qiu SJ et al.. Circulating stem cell–like epithelial cell adhesion molecule-positive tumor cells indicate poor prognosis of hepatocellular carcinoma after curative resection. Hepatology. 2013; 57:1458-1468.
• [46]Wang CC, Iyer SG, Low JK, Lin CY, Wang SH, Lu SN et al.. Perioperative factors affecting long-term outcomes of 473 consecutive patients undergoing hepatectomy for hepatocellular carcinoma. Ann Surg Oncol. 2009; 16:1832-1842.