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Meta-Analysis
. 2017 Sep 5;117(6):856-866.
doi: 10.1038/bjc.2017.244. Epub 2017 Jul 27.

Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis

Alhadi Almangush  1   2   3 , Ilkka Heikkinen  1   2 , Antti A Mäkitie  4 , Ricardo D Coletta  5 , Esa Läärä  6 , Ilmo Leivo  7 , Tuula Salo  2   8   9   10
Affiliations
Meta-Analysis

Prognostic biomarkers for oral tongue squamous cell carcinoma: a systematic review and meta-analysis

Alhadi Almangush et al. Br J Cancer. .

Abstract

Background: Identifying informative prognostic biomarkers for oral tongue squamous cell carcinoma (OTSCC) is of great importance in order to better predict tumour behaviour and to guide treatment planning. Here, we summarise existing evidence regarding immunohistochemical prognostic biomarkers for OTSCC.

Methods: A systematic search of the literature was performed using the databases of Scopus, Ovid Medline, Web of Science and Cochrane Library. All studies which had investigated the prognostic significance of immunohistochemical biomarkers in OTSCC during the period from 1985 to 2015 were retrieved. For the five most often evaluated biomarkers a random-effects meta-analysis on overall survival was performed, including those studies that provided the necessary statistical results.

Results: A total of 174 studies conducted during the last three decades were found, and in these 184 biomarkers were evaluated for the prognostication of OTSCC. The five biomarkers most frequently assessed were p53, Ki-67, p16, VEGFs and cyclin D1. In the meta-analyses, the most promising results of the prognostic power for OTSCC were obtained for cyclin D1. For studies of VEGF A and C the results were equivocal, but the pooled analysis of VEGF A separately showed it to be a useful prognosticator for OTSCC. There was no sufficient evidence to support p53, Ki-67 and p16 as prognostic biomarkers for OTSCC. Limitations in the quality of the published studies (e.g., small cohorts, lack of compliance with REMARK guidelines) are widespread.

Conclusions: Numerous biomarkers have been presented as useful prognosticators for OTSCC, but the quality of the conduct and reporting of original studies is overall unsatisfactory which does not allow reliable conclusions. The value of two biomarkers (VEGF-A and cyclin D1) should be validated in a multicentre study setting following REMARK guidelines.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart: studies included and excluded along the various steps.
Figure 2
Figure 2
Biomarkers evaluated in three studies or more for their prognostic value in OTSCC.
Figure 3
Figure 3
Forest plots for the pooled analyses of the biomarkers that have been studied most frequently in OTSCC but did not have prognostic usefulness in OTSCC. (A) p53 studies, (B) Ki-67 studies, and (C) p16 studies.
Figure 4
Figure 4
Forest plots for the pooled analyses of the biomarkers that have been studied most frequently in OTSCC and have shown prognostic usefulness in OTSCC. (A) VEGFs studies and (B) cyclin D1 studies.
See this image and copyright information in PMC

Comment in

References

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