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      The prognostic value of lactate dehydrogenase levels in colorectal cancer: a meta-analysis

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          Abstract

          Background

          The prognostic value of lactate dehydrogenase levels in the prognosis of colorectal cancer patients has been assessed for years, although the results remain controversial and heterogeneous. Thus, we comprehensively reviewed the evidence from studies that evaluated lactate dehydrogenase levels in colorectal cancer patients to determine their effect.

          Methods

          The following databases were searched in September 2014 to identify studies that evaluated the prognostic value of lactate dehydrogenase levels in colorectal cancer: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. We extracted hazard ratios (HRs) and the associated 95 % confidence intervals (CIs) from the identified studies, and performed random-effects model meta-analyses on the overall survival (OS) and progression-free survival (PFS). Thirty-two studies with a cumulative sample size of 8,261 patients were included in our analysis.

          Results

          Our meta-analyses revealed that high levels of lactate dehydrogenase were associated with poor OS (HR, 1.75; 95 % CI, 1.52–2.02) in colorectal cancer patients. However, this effect was not obvious in the OS of non-metastatic colorectal cancer patients (HR, 1.21; 95 % CI, 0.79–1.86). The prognostic value of lactate dehydrogenase levels on PFS was also not confirmed (HR, 1.36; 95 % CI, 0.98–1.87). Subgroup analyses revealed that the prognostic significance of lactate dehydrogenase was independent of study location, patient age, number of patients, metastasis, chemotherapy with anti-angiogenesis drugs, study type, or risk of bias.

          Conclusions

          Our results indicate that high lactate dehydrogenase levels are associated with poor OS among colorectal cancer patients, although these levels are not significant predictors of PFS.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12885-016-2276-3) contains supplementary material, which is available to authorized users.

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          Most cited references43

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          Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints.

          M Parmar, V. Torri, L. Stewart (1998)
          Meta-analyses aim to provide a full and comprehensive summary of related studies which have addressed a similar question. When the studies involve time to event (survival-type) data the most appropriate statistics to use are the log hazard ratio and its variance. However, these are not always explicitly presented for each study. In this paper a number of methods of extracting estimates of these statistics in a variety of situations are presented. Use of these methods should improve the efficiency and reliability of meta-analyses of the published literature with survival-type endpoints.
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            Targeting lactate metabolism for cancer therapeutics.

            Joanne R. Doherty, John L. Cleveland (2013)
            Lactate, once considered a waste product of glycolysis, has emerged as a critical regulator of cancer development, maintenance, and metastasis. Indeed, tumor lactate levels correlate with increased metastasis, tumor recurrence, and poor outcome. Lactate mediates cancer cell intrinsic effects on metabolism and has additional non-tumor cell autonomous effects that drive tumorigenesis. Tumor cells can metabolize lactate as an energy source and shuttle lactate to neighboring cancer cells, adjacent stroma, and vascular endothelial cells, which induces metabolic reprogramming. Lactate also plays roles in promoting tumor inflammation and in functioning as a signaling molecule that stimulates tumor angiogenesis. Here we review the mechanisms of lactate production and transport and highlight emerging evidence indicating that targeting lactate metabolism is a promising approach for cancer therapeutics.
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              Meta-analysis shows that detection of circulating tumor cells indicates poor prognosis in patients with colorectal cancer.

              Markus K. Diener, N Mollberg, Markus W. Büchler … (2010)
              The prognostic significance of circulating (CTCs) and disseminated tumor cells in patients with colorectal cancer (CRC) is controversial. We performed a meta-analysis of available studies to assess whether the detection of tumor cells in the blood and bone marrow (BM) of patients diagnosed with primary CRC can be used as a prognostic factor. We searched the Medline, Biosis, Science Citation Index, and Embase databases and reference lists of relevant articles (including review articles) for studies that assessed the prognostic relevance of tumor cell detection in the peripheral blood (PB), mesenteric/portal blood (MPB), or BM of patients with CRC. Meta-analyses were performed using a random effects model, with hazard ratio (HR) and 95% confidence intervals (95% CIs) as effect measures. A total of 36 studies, including 3094 patients, were eligible for final analyses. Pooled analyses that combined all sampling sites (PB, MPB, and BM) associated the detection of tumor cells with poor recurrence-free survival (RFS) (HR = 3.24 [95% CI: 2.06-5.10], n = 26, I(2) = 77%) and overall survival (OS) (2.28 [1.55-3.38], n = 21, I(2) = 66%). Stratification by sampling site showed that detection of tumor cells in the PB compartment was a statistically significant prognostic factor (RFS: 3.06 [1.74-5.38], n = 19, I(2) = 78%; OS: 2.70 [1.74-4.20], n = 16, I(2) = 59%) but not in the MPB (RFS: 4.12 [1.01-16.83], n = 8, I(2) = 75%; OS: 4.80 [0.81-28.32], n = 5, I(2) = 82%) or in the BM (RFS: 2.17 [0.94-5.03], n = 4, I(2) = 78%; OS: 1.50 [0.52-4.32], n = 3, I(2) = 84%). Detection of CTCs in the PB indicates poor prognosis in patients with primary CRC. Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Guanghua Li: lgh8711@gmail.com
                Zhao Wang: drzhaowang@163.com
                Jianbo Xu: 447527535@qq.com
                Hui Wu: docwuhui@126.com
                Shirong Cai: srcai2008@126.com
                Yulong He: 020-28823389 , lgh8711@126.com
                Journal
                Journal ID (nlm-ta): BMC Cancer
                Journal ID (iso-abbrev): BMC Cancer
                Title: BMC Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1471-2407
                Publication date (Electronic): 25 March 2016
                Publication date PMC-release: 25 March 2016
                Publication date Collection: 2016
                Volume: 16
                Electronic Location Identifier: 249
                Affiliations
                Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-sen University, 510080 Guangzhou, Guangdong Province People’s Republic of China
                Article
                Publisher ID: 2276
                DOI: 10.1186/s12885-016-2276-3
                PMC ID: 4807548
                PubMed ID: 27016045
                SO-VID: 5df4af4a-5e12-4d80-afc8-bd7ff11afbee
                Copyright © © Li et al. 2016
                License:

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 22 March 2015
                Date accepted : 13 March 2016
                Categories
                Subject: Research Article
                Custom metadata
                issue-copyright-statement © The Author(s) 2016

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: lactate dehydrogenase,colorectal cancer,prognosis,meta-analysis
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: lactate dehydrogenase, colorectal cancer, prognosis, meta-analysis

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