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      Preoperative Anemia or Low Hemoglobin Predicts Poor Prognosis in Gastric Cancer Patients: A Meta-Analysis

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          Abstract

          Background

          The prognostic value of preoperative anemia in gastric cancer remains unclear. Therefore, the purpose of the present study is to evaluate the prognostic value of preoperative anemia in gastric cancer.

          Methods

          We searched Embase and PubMed databases for relevant studies from inception to March 2018. The prognostic value of preoperative anemia in gastric cancer was determined by calculating the hazard ratio (HR) and the corresponding 95% confidence interval (CI) as effect measures. A random effect model was used in cases in which there was significant heterogeneity; otherwise, a fixed effect model was used. Statistical analyses were performed using Stata software.

          Results

          Seventeen studies involving 13,154 gastric cancer patients were included. The estimated rate of preoperative anemia was 36% (95%CI = 27-44%). The overall survival of preoperative anemia was poor (HR = 1.33, 95%CI = 1.21-1.45). Moreover, disease-free survival was significantly lower in patients with preoperative anemia compared with those without this condition (HR = 1.62, 95%CI = 1.13-2.32). These findings were corroborated by the results of subgroup analyses.

          Conclusions

          The results indicate that preoperative anemia predicts poor prognosis in gastric cancer, including overall survival and disease-free survival. Therefore, preoperative anemia may be a convenient and cost-effective blood-derived prognostic marker for gastric cancer.

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          Most cited references39

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          The role of hypoxia-induced factors in tumor progression.

          Peter Vaupel (2004)
          Hypoxia is a common characteristic of locally advanced solid tumors that has been associated with diminished therapeutic response and, more recently, with malignant progression, that is, an increasing probability of recurrence, locoregional spread, and distant metastasis. Emerging evidence indicates that the effect of hypoxia on malignant progression is mediated by a series of hypoxia-induced proteomic and genomic changes activating angiogenesis, anaerobic metabolism, and other processes that enable tumor cells to survive or escape their oxygen-deficient environment. The transcription factor hypoxia-inducible factor 1 (HIF-1) is a major regulator of tumor cell adaptation to hypoxic stress. Tumor cells with proteomic and genomic changes favoring survival under hypoxic conditions will proliferate, thereby further aggravating the hypoxia. The selection and expansion of new (and more aggressive) clones, which eventually become the dominant tumor cell type, lead to the establishment of a vicious circle of hypoxia and malignant progression.
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            Hypoxia, clonal selection, and the role of HIF-1 in tumor progression.

            G Semenza (1999)
            Tumor progression occurs as a result of the clonal selection of cells in which somatic mutations have activated oncogenes or inactivated tumor suppressor genes leading to increased proliferation and/or survival within the hypoxic tumor microenvironment. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates adaptive responses to reduced O2 availability, including angiogenesis and glycolysis. Expression of the O2-regulated HIF-1alpha subunit and HIF-1 transcriptional activity are increased dramatically in hypoxic cells. Recent studies indicate that many common tumor-specific genetic alterations also lead to increased HIF-1alpha expression and/or activity. Thus, genetic and physiologic alterations within tumors act synergistically to increase HIF-1 transcriptional activity, which appears to play a critical role in the development of invasive and metastatic properties that define the lethal cancer phenotype.
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              Prevalence and outcomes of anemia in cancer: a systematic review of the literature.

              Lodovico Balducci, Sally Wade, Kevin Knight (2004)
              Anemia is common in patients with cancer. This systematic literature review of reports published in 1966 through February 2003 identified the prevalence of anemia in specific cancers and assessed the impact of anemia on survival and quality of life (QOL). Studies about chemotherapy-induced anemia were excluded. Anemia prevalence varied widely; most studies found that between 30% and 90% of patients with cancer had anemia. Prevalence was affected strongly by the definition of anemia: 7% of patients with Hodgkin disease had anemia when the condition was defined as a hemoglobin level <90.0 g/L; as many as 86% of patients had anemia when it was defined as a hemoglobin value <110.0 g/L. Prevalence varied by cancer type and disease stage: 40% of patients with early-stage colon tumors and nearly 80% of patients with advanced disease had anemia. Patients with anemia had poorer survival and local tumor control than did their nonanemic counterparts in 15 of 18 studies. In 8 of 12 studies, patients without anemia (most treated with epoetin) needed fewer transfusions. QOL was positively correlated with hemoglobin levels in 15 of 16 studies. There was no significant difference in treatment toxicity between patients with and without anemia. Tumor hypoxia, which has been associated with resistance to radiation therapy and chemotherapy, may stimulate angiogenesis, leading to poor local control of tumors and increased morbidity and mortality. Treatment of anemia may have a significant impact on patient survival and QOL. However, a standard definition of anemia is needed, as is research about the effect of anemia on cancer progression.
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                Author and article information

                Contributors
                Zhen-ning Wang:
                ORCID: http://orcid.org/0000-0003-0557-3097
                Xi Zhang:
                ORCID: http://orcid.org/0000-0001-7033-8478
                Journal
                Journal ID (nlm-ta): Dis Markers
                Journal ID (iso-abbrev): Dis. Markers
                Journal ID (publisher-id): DM
                Title: Disease Markers
                Publisher: Hindawi
                ISSN (Print): 0278-0240
                ISSN (Electronic): 1875-8630
                Publication date Collection: 2019
                Publication date (Electronic): 2 January 2019
                Volume: 2019
                Electronic Location Identifier: 7606128
                Affiliations
                1Department of Chemotherapy and Radiotherapy, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Lucheng District, Wenzhou City 325027, China
                2Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin 300060, China
                3Wenzhou Dental Hospital, 197 Fuqian Street, Lucheng District, Wenzhou City 325027, China
                4Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, China
                Author notes

                Academic Editor: Giuseppe Biondi-Zoccai

                Author information
                http://orcid.org/0000-0003-0557-3097
                http://orcid.org/0000-0001-7033-8478
                Article
                DOI: 10.1155/2019/7606128
                PMC ID: 6334363
                PubMed ID: 30719182
                SO-VID: 08dc9ca8-3b76-4fc3-94b2-a78660373055
                Copyright © Copyright © 2019 Xuan-zhang Huang et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 8 September 2018
                Date revision received : 17 October 2018
                Date accepted : 25 November 2018
                Funding
                Funded by: Tianjin Medical University Cancer Institute and Hospital, and Department of Surgical Oncology of the First Hospital of China Medical University
                Funded by: Chemotherapy and Radiotherapy of the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
                Categories
                Subject: Review Article

                Data availability:

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