Metallothionein - immunohistochemical cancer biomarker: a meta-analysis

Jaromir Gumulec; Martina Raudenska; Vojtech Adam; Rene Kizek; Michal Masarik

doi:10.1371/journal.pone.0085346

Metallothionein - immunohistochemical cancer biomarker: a meta-analysis

PLoS One. 2014 Jan 8;9(1):e85346. doi: 10.1371/journal.pone.0085346. eCollection 2014.

Authors

Jaromir Gumulec¹, Martina Raudenska¹, Vojtech Adam², Rene Kizek², Michal Masarik¹

Affiliations

¹ Department of Pathological Physiology, Masaryk University, Brno, Czech Republic ; Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic.
² Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic ; Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic.

Abstract

Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review. Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests. A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82-17.03) and ovarian tumors (OR 7.83; 1.09-56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03-0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08-2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03-2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47-2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer. Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / metabolism*
Case-Control Studies
Databases, Bibliographic
Female
Head and Neck Neoplasms / diagnosis
Head and Neck Neoplasms / metabolism*
Head and Neck Neoplasms / pathology
Humans
Immunohistochemistry
Liver Neoplasms / diagnosis
Liver Neoplasms / metabolism*
Liver Neoplasms / pathology
Metallothionein / metabolism*
Neoplasm Grading
Neoplasm Metastasis
Odds Ratio
Ovarian Neoplasms / diagnosis
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology
Prognosis

Substances

Biomarkers, Tumor
Metallothionein

Grants and funding

Financial support from Central European Institute of Technology (CEITEC CZ.1.05/1.1.00/02.0068) and Internal Grant Agency of Ministry of Health of the Czech Republic (IGA MH NT14337-3/2013) is acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.