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      Prognostic Significance of Systemic Inflammation-Based Lymphocyte- Monocyte Ratio in Patients with Lung Cancer: Based on a Large Cohort Study

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          Abstract

          Increasing evidence indicates cancer-related inflammatory biomarkers show great promise for predicting the outcome of cancer patients. The lymphocyte- monocyte ratio (LMR) was demonstrated to be independent prognostic factor mainly in hematologic tumor. The aim of the present study was to investigate the prognostic value of LMR in operable lung cancer. We retrospectively enrolled a large cohort of patients with primary lung cancer who underwent complete resection at our institution from 2006 to 2011. Inflammatory biomarkers including lymphocyte count and monocyte count were collected from routinely performed preoperative blood tests and the LMR was calculated. Survival analyses were calculated for overall survival (OS) and disease-free survival (DFS). A total of 1453 patients were enrolled in the study. The LMR was significantly associated with OS and DFS in multivariate analyses of the whole cohort (HR = 1.522, 95% CI: 1.275–1.816 for OS, and HR = 1.338, 95% CI: 1.152–1.556 for DFS). Univariate subgroup analyses disclosed that the prognostic value was limited to patients with non-small-cell lung cancer (NSCLC) (HR: 1.824, 95% CI: 1.520–2.190), in contrast to patients with small cell lung cancer (HR: 1.718, 95% CI: 0.946–3.122). Multivariate analyses demonstrated that LMR was still an independent prognostic factor in NSCLC. LMR can be considered as a useful independent prognostic marker in patients with NSCLC after complete resection. This will provide a reliable and convenient biomarker to stratify high risk of death in patients with operable NSCLC.

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          Role of systemic inflammatory response in predicting survival in patients with primary operable cancer.

          Campbell Roxburgh, Donald C. McMillan (2010)
          Disease progression in cancer is dependent on the complex interaction between the tumor and the host inflammatory response. There is substantial evidence in advanced cancer that host factors, such as weight loss, poor performance status and the host systemic inflammatory response, are linked, and the latter is an important tumor-stage-independent predictor of outcome. Indeed, the systemic inflammatory response, as evidenced by an elevated level of C-reactive protein, is now included in the definition of cancer cachexia. This review examines the role of the systemic inflammatory response in predicting survival in patients with primary operable cancer. Approximately 80 studies have evaluated the role of the systemic inflammatory response using biochemical or hematological markers, such as elevated C-reactive protein levels, hypoalbuminemia or increased white cell, neutrophil and platelet counts. Combinations of such factors have been used to derive simple inflammation-based prognostic scores, such as the Glasgow Prognostic Score, the neutrophil:lymphocyte ratio and the platelet:lymphocyte ratio. This review demonstrates that there is now good evidence that preoperative measures of the systemic inflammatory response predict cancer survival, independent of tumor stage, in primary operable cancer. The evidence is particularly robust in colorectal (including liver metastases), gastro-esophageal and renal cancers. As described in this article, measurement of the systemic inflammatory response is simple, reliable and can be clinically incorporated into current staging algorithms. This will provide the clinician with a better prediction of outcome, and therefore better treatment allocation in patients with primary operable cancer. Furthermore, systemic inflammation-based markers and prognostic scores not only identify patients at risk, but also provide well-defined therapeutic targets for future clinical trials.
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            Macrophages regulate the angiogenic switch in a mouse model of breast cancer.

            Elaine Y Lin, Jiu-Feng Li, Leoid Gnatovskiy … (2006)
            The development of a tumor vasculature or access to the host vasculature is a crucial step for the survival and metastasis of malignant tumors. Although therapeutic strategies attempting to inhibit this step during tumor development are being developed, the biological regulation of this process is still largely unknown. Using a transgenic mouse susceptible to mammary cancer, PyMT mice, we have characterized the development of the vasculature in mammary tumors during their progression to malignancy. We show that the onset of the angiogenic switch, identified as the formation of a high-density vessel network, is closely associated with the transition to malignancy. More importantly, both the angiogenic switch and the progression to malignancy are regulated by infiltrated macrophages in the primary mammary tumors. Inhibition of the macrophage infiltration into the tumor delayed the angiogenic switch and malignant transition whereas genetic restoration of the macrophage population specifically in these tumors rescued the vessel phenotype. Furthermore, premature induction of macrophage infiltration into premalignant lesions promoted an early onset of the angiogenic switch independent of tumor progression. Taken together, this study shows that tumor-associated macrophages play a key role in promoting tumor angiogenesis, an essential step in the tumor progression to malignancy.
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              Neutrophil/lymphocyte ratio and its association with survival after complete resection in non-small cell lung cancer.

              Khaled Sarraf, Elizabeth Belcher, Evgeny Raevsky … (2009)
              Increasing neutrophil/lymphocyte ratios on preoperative blood tests have been associated with worse survival after resection of colorectal cancer. We sought to determine factors associated with increasing neutrophil/lymphocyte ratios and the stage-adjusted prognostic effect in patients undergoing resection for non-small cell lung cancer. We performed a retrospective review of patients undergoing complete resection for non-small cell lung cancer between 1999 and 2005. Data acquisition was through patient medical records, blood results recorded on admission before surgical intervention, and follow-up by National Health Service database searches and hospital records. Cox proportional hazards regression was used to estimate the effect of neutrophil/lymphocyte ratio on stage-adjusted survival. During the study period, 178 patients underwent pulmonary resection. Of 177 patients, the majority were male 104 (59%), with a mean age of 63 years (standard deviation, 10 years). The median follow-up time was 29 months (interquartile range, 8-56 months), and overall survival was 83% and 54% at 1 and 5 years, respectively. Higher stage was the only factor found to be associated with increasing neutrophil/lymphocyte ratios (P = .019). Total white cell count (P = .990) and neutrophil count (P = .490), age (P = .290), and cell type (P = .490) were not significant predictors of mortality. On multivariable analysis after adjusting for stage, increasing neutrophil/lymphocyte ratios (hazard ratio, 1.10; 95% confidence interval, 1.03-1.17; P = .004) remained an independent prognostic indicator. Increasing preoperative neutrophil/lymphocyte ratios are associated with higher stage but remain an independent predictor of survival after complete resection for primary lung cancer and are a potential biomarker to stratify high risk of death in patients with stage I disease.
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                Author and article information

                Contributors
                Wafik S. El-Deiry: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2014
                Publication date (Electronic): 2 October 2014
                Volume: 9
                Issue: 10
                Electronic Location Identifier: e108062
                Affiliations
                [1 ]Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
                [2 ]Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
                [3 ]Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Shandong University, Jinan, China
                Penn State Hershey Cancer Institute, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: PH QL JD. Performed the experiments: PH HS GW. Analyzed the data: PH GW PZ. Contributed reagents/materials/analysis tools: PH GW PZ. Wrote the paper: PH PZ.

                Article
                Publisher ID: PONE-D-14-32976
                DOI: 10.1371/journal.pone.0108062
                PMC ID: 4183469
                PubMed ID: 25275631
                SO-VID: e49d4647-e116-4281-9665-9a5887f5ae35
                Copyright statement: Copyright @ 2014
                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 : 23 July 2014
                Date accepted : 19 August 2014
                Page count
                Pages: 6
                Funding
                The work was supported by National Natural Science Foundation of China (81301728), Provincial Natural Science Foundation of Shandong (ZR2013HZ001), and Provincial Science and Technology Development Plan of Shandong (2012G0021836). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Medicine and Health Sciences
                Subject: Oncology
                Subject: Cancer Detection and Diagnosis
                Subject: Cancer Screening
                Subject: Cancers and Neoplasms
                Subject: Lung and Intrathoracic Tumors
                Subject: Non-Small Cell Lung Cancer
                Subject: Small Cell Lung Cancer
                Subject: Cancer Prevention
                Custom metadata
                Data Availability The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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