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      Prognostic significance of preoperative aspartate aminotransferase to neutrophil ratio index in patients with hepatocellular carcinoma after hepatic resection

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          Abstract

          Objectives

          Various inflammation-based prognostic scores have been associated with poor survival in patients with hepatocellular carcinoma (HCC), and neutrophils display important roles. However, few studies have illuminated the relationship between preoperative aspartate aminotransferase (AST) to neutrophil ratio index (ANRI) and poor prognosis of HCC. We aimed to clarify the prognostic value of ANRI and evaluate the ability of different inflammation-based prognostic scores such as ANRI, AST to lymphocyte ratio index (ALRI), AST to platelet count ratio index (APRI), neutrophil-lymphocyte ratio index (NLR), and platelet-lymphocyte ratio index (PLR).

          Methods

          Data were collected retrospectively from 303 patients who underwent curative resection for HCC. Preoperative ANRI, ALRI, APRI, NLR, PLR and clinico-pathological variables were analyzed. Univariate, multivariate and Kaplan-Meier analyses were performed to identify the predictive value of the above factors for disease-free survival (DFS) and overall survival (OS).

          Results

          ANRI was correlated with presence of HBsAg, AST, presence of cirrhosis, tumor size, PVTT, cancer of the liver Italian program (CLIP) score, recurrence. Univariate analysis showed ANRI, ALRI, APRI, NLR, PLR were significantly associated with DFS and OS in HCC patients with curative resection. After multivariate analysis, ANRI was demonstrated to be superior to ALRI, APRI, NLR, PLR, which were independently correlated with DFS and OS. Survival analysis showed that preoperative ANRI > 7.8 predicted poor prognosis of patients with HCC after hepatectomy. preoperative ANRI also showed different prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of ANRI and NLR.

          Conclusions

          preoperative ANRI is an independent effective predictor of prognosis for patients with HCC, higher levels of ANRI predict poorer outcomes and the combining ANRI and NLR increases the prognostic accuracy of testing.

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          Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression.

          Marisa Queen, Randall E Ryan, Ryan Holzer … (2005)
          Tumor-associated and tumor-infiltrating neutrophils (TAN) and macrophages (TAM) can account for as much as 50% of the total tumor mass in invasive breast carcinomas. It is thought that tumors secrete factors that elicit a wound-repair response from TAMs and TANs and that this response inadvertently stimulates tumor progression. Oncostatin M is a pleiotropic cytokine belonging to the interleukin-6 family that is expressed by several cell types including activated human T lymphocytes, macrophages, and neutrophils. Whereas oncostatin M can inhibit the proliferation of breast cancer cells in vitro, recent studies suggest that oncostatin M may promote tumor progression by enhancing angiogenesis and metastasis. In addition, neutrophils can be stimulated to synthesize and rapidly release large quantities of oncostatin M. In this article, we show that human neutrophils secrete oncostatin M when cocultured with MDA-MB-231 and T47D human breast cancer cells. Neutrophils isolated from whole blood or breast cancer cells alone express little oncostatin M by immunocytochemistry and ELISA, but neutrophils express and release high levels of oncostatin M when they are cocultured with breast cancer cells. In addition, we show that granulocyte-macrophage colony-stimulating factor produced by breast cancer cells and cell-cell contact are both necessary for the release of oncostatin M from neutrophils. Importantly, neutrophil-derived oncostatin M induces vascular endothelial growth factor from breast cancer cells in coculture and increases breast cancer cell detachment and invasive capacity, suggesting that neutrophils and oncostatin M may promote tumor progression in vivo.
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            Intratumoral neutrophils: a poor prognostic factor for hepatocellular carcinoma following resection.

            Shuang Qiu, Jian Zhou, FAN-FAN XING … (2011)
            Neutrophil infiltration has been linked to clinical outcome of various cancer types. However, its role in hepatocellular carcinoma (HCC) is unclear. In this study, we investigated prognostic values for intratumoral and peritumoral neutrophils in HCC patients undergoing curative resection. The expression of CD66b, CD8, TGF-beta, and CD34 was assessed by immunohistochemistry in tissue microarrays containing paired intratumoral and peritumoral tissues from 197 patients receiving curative resection for HCC. Prognostic values for these and other clinicopathologic factors were evaluated. Intratumoral CD66b(+) neutrophils significantly correlated with CD8(+) T cells (r=0.240, p=0.004), TGF-beta expression (p=0.012), BCLC stage (p=0.016), and early recurrence (p=0.041). Increased intratumoral neutrophils were significantly associated with decreased RFS/OS (p=0.001 and p<0.001, respectively) in univariate analysis and were identified as an independent prognostic factor (HR=1.845, 95% CI=1.169-2.911, p=0.008 for RFS; HR=2.578, 95% CI=1.618-4.106, p<0.001 for OS) in multivariate analysis. Intratumoral neutrophil-to-CD8(+) T cell ratio (iNTR) better predicted the outcome in terms of minimum p values. Intratumoral neutrophils were also demonstrated to be statistically predictive for RFS/OS in the normal AFP subgroup, small HCC subgroup, and validation cohort. However, peritumoral neutrophils were not associated with the outcome of HCC. The presence of intratumoral neutrophils was a poor prognostic factor for HCC after resection. Intratumoral neutrophil-to-CD8(+) T cell ratio was a better predictor of outcome. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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              Pretreatment neutrophil count as an independent prognostic factor in advanced non-small-cell lung cancer: an analysis of Japan Multinational Trial Organisation LC00-03.

              Satoshi Teramukai, Toshiyuki Kitano, Yusuke Kishida … (2009)
              We examined the impact of pretreatment neutrophil count on survival in patients with advanced non-small-cell lung cancer (NSCLC). A total of 388 chemo-naïve patients with stage IIIB or IV NSCLC from a randomised controlled trial were evaluated. The effects of pretreatment peripheral blood neutrophil, lymphocyte and monocyte counts and neutrophil-lymphocyte ratio on survival were examined using the proportional hazards regression model to estimate hazard ratios after adjustment for covariates. The optimal cut-off value was determined by proportional hazards regression analysis with the minimum P-value approach and shrinkage procedure. After adjustment for prognostic factors, the pretreatment elevated neutrophil count was statistically significantly associated with short overall (P=0.0008) and progression-free survival (P=0.024), whereas no association was found between prognosis and lymphocyte or monocyte count. The cut-off value selected for neutrophil count was 4500 mm(-3) (corrected hazard ratio, 1.67; 95% confidence interval (CI), 1.09-2.54). The median survival time was 19.3 months (95%CI, 16.5-21.4) for the low-neutrophil group (4500 mm(-3), n=204) and was 10.2 months (95%CI, 8.0-12.3) for the high-neutrophil group (4500 mm(-3), n=184). We confirmed that pretreatment elevated neutrophil count is an independent prognostic factor in patients with advanced NSCLC receiving modern chemotherapy. Neutrophil count is easily measured at low cost, and it may be a useful indicator of patient prognosis.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oncotarget
                Journal ID (iso-abbrev): Oncotarget
                Journal ID (publisher-id): Oncotarget
                Journal ID (publisher-id): ImpactJ
                Title: Oncotarget
                Publisher: Impact Journals LLC
                ISSN (Electronic): 1949-2553
                Publication date Collection: 1 November 2016
                Publication date (Electronic): 26 July 2016
                Volume: 7
                Issue: 44
                Pages: 72276-72289
                Affiliations
                1 Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
                2 Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology, Guangzhou, P. R. China
                3 Guangdong Provincial International Cooperation Base of Science and Technology (Organ Transplantation), Guangzhou, P. R. China
                4 Department of Medical Records, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
                5 Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
                6 Department of Liver Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P. R. China
                Author notes
                Correspondence to: Baogang Peng, pengbaogang@ 123456medmail.com.cn
                Xiaoshun He, gdtrc@ 123456163.com
                Article
                Publisher ID: 10848
                DOI: 10.18632/oncotarget.10848
                PMC ID: 5342161
                PubMed ID: 27472390
                SO-VID: 261dc811-9e9d-40fc-bc88-cb2a02277811
                Copyright © Copyright: © 2016 Ji et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 6 February 2016
                Date accepted : 9 July 2016
                Categories
                Subject: Clinical Research Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: aspartate aminotransferase to neutrophil ratio index,systemic immune-inflammation,hepatocellular carcinoma,prognosis,biomarkers
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: aspartate aminotransferase to neutrophil ratio index, systemic immune-inflammation, hepatocellular carcinoma, prognosis, biomarkers

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