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Review
. 2018 Dec 27:18:217.
doi: 10.1186/s12935-018-0715-8. eCollection 2018.

Immunohistochemical investigation of prognostic biomarkers in resected colorectal liver metastases: a systematic review and meta-analysis

William Torén  1 , Daniel Ansari  1 , Roland Andersson  1
Affiliations
Review

Immunohistochemical investigation of prognostic biomarkers in resected colorectal liver metastases: a systematic review and meta-analysis

William Torén et al. Cancer Cell Int. .

Abstract

Background: Many studies have investigated the prognostic role of biomarkers in colorectal liver metastases (CRLM). However, no biomarker has been established in routine clinical practice. The aim of this study was to scrutinize the current literature for biomarkers evaluated by immunohistochemistry as prognostic markers in patients with resected CRLM.

Methods: A systematic review was performed according to the PRISMA guidelines. Articles were identified in the PubMed database with selected search terms and by cross-references search. The REMARK quality criteria were applied. Markers were included if they reported the prognostic impact of immunohistochemical markers in a multivariable setting in relation to overall survival (OS). A meta-analysis was conducted when more than one original article provided survival data of a marker.

Results: In total, 26 biomarkers were identified as independent significant markers for OS in resected CRLM. These biomarkers were found to be involved in multiple oncogenic signalling pathways that control cell growth, apoptosis, angiogenesis and evasion of immune detection. Among these biomarker candidates were Ki-67, EGFR, p53, hTERT, CD34, TSP-1, KISS1, Aurora kinase A and CDX2. CD34 and TSP-1 were reported as significantly associated with survival by more than one study and where therefore pooled in a meta-analysis.

Conclusion: A number of independent prognostic biomarkers for resected CRLM were identified. However, most markers were evaluated in a retrospective setting with small patient cohorts, without external validation. Large, prospective, multicentre studies with standardised methods are needed before biomarkers can translated into the clinic.

Keywords: Biomarkers; Colorectal liver metastasis; Immunohistochemistry; Prognosis; Tissue microarray.

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Figures

Fig. 1
Fig. 1
Search strategy
Fig. 2
Fig. 2
Forest plot of association between CD34 expression and survival after resection of CRLM. A fixed-effect model was used for meta-analysis
Fig. 3
Fig. 3
Forest plot of association between TSP-1 expression and survival after resection of CRLM. A fixed-effect model was used for meta-analysis
Fig. 4
Fig. 4
Functional relevance of selected biomarker candidates
See this image and copyright information in PMC

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