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and meta-analysis to specifically investigate and compare
EN2 as a possible biomarker for PCa.
According to Pandha et al.,
14
EN2 test can lead to
faster diagnosis, saving thousands of lives, and has the
potential to reduce the cost of disease. However, it has
the disadvantage of not providing disease progression or
predicting tumor recurrence.
To date, the PSA is the most widely used tumor bio-
marker to detect, track and monitor PCa. In the literature,
there are still differences regarding the use of PSA in-
dicative of biopsy to confirm cancer. There is a lack of
consensus among the authors on the ideal point. This
contributes substantially to the great heterogeneity be-
tween the studies.
15
Interestingly, there are few published studies assessing
EN2 protein in PCa because it is a relatively new subject. It
is thus necessary to conduct further studies so that we can
understand the actual link between the EN2 protein and
PCa, as well as in other types of neoplasias, such as breast
cancer. Certainly, the development of new studies on this
subject is essential to come up with a fast, accurate and
primary diagnosis in cancer evaluation.
Considering the high specificity of EN2 and the high
sensitivity of PSA, we hypothesize that using both tests
together would increase the likelihood of PCa diagnosis.
Thus, we suggest future studies to investigate if this oc-
curs in the practice.
We used the GRADE approach to assess the quality of
the evidence produced in this study, classifying it as low,
which means that “further research is very likely to have
an important impact on our confidence in the estimate of
effect and is likely to change the estimate or any estimate
of effect is very uncertain.” The evidence was downgraded
due to risk of bias (limitations in the study design and
execution) and indirectness (differences in patients, time
and flow of tests) across the included studies.
A limitation of this study is that some of the includ-
ed control patients did not undergo prostate biopsy. The
study protocol includes annual PSA screening for 5 years,
at which point recruits are offered an optional prostate
biopsy; approximately half of the 392 individuals with
PSA 3.0 ng/mL will undergo prostate biopsy. However,
we decided to include this study because all PCa patients
included were diagnosed by biopsy and did not present
heterogeneity between the studies.
C
onclusion
The low sensitivity and high specificity must be analyzed
carefully, since there are few studies analyzing EN2 and
the quality of evidence is low. It is too early to recommend
EN2 for detection and/or screening of PCa.
C
onflict
of
interest
The authors declare no conflict of interest.
R
esumo
Proteína EN2 urinária no diagnóstico do câncer de prósta-
ta: revisão sistemática e metanálise
Introdução:
O câncer de próstata é o segundo tipo de
câncer diagnosticado e a quinta causa de morte em ho-
mens em todo o mundo. O diagnóstico precoce é funda-
mental para o prognóstico da doença. Atualmente, o
antígeno específico da próstata (PSA) é o biomarcador
mais utilizado; porém, biomarcadores mais específicos
devem ser estudados.
Objetivo:
Avaliar a acurácia da proteína engrenada-2 (EN2)
na urina como biomarcador de câncer de próstata.
Método:
Foi realizada uma busca abrangente no período
de janeiro de 2005 a julho de 2016, utilizando as seguintes
bases de dados eletrônicas: Medline (PubMed), Embase,
Cochrane Library e Lilacs. As palavras-chave utilizadas
foram: “engrailed-2”, “EN2”, “prostatic neoplasms”. A bus-
ca foi limitada a humanos e não houve restrição de idioma.
A avaliação da qualidade dos estudos incluídos foi realiza-
da de acordo com Quadas-2. A análise estatística foi reali-
zada usando o software Meta-DiSc® e RevMan 5.3.
Resultados:
Foram identificados 248 estudos. Após a
triagem dos títulos e resumos, foram excluídos 231. Um
total de 17 foram lidos na íntegra e dois, incluídos na
metanálise. A sensibilidade combinada foi de 66% (IC95%
0,56-0,75). A especificidade foi de 89% (IC95% 0,86-0,92).
O DOR foi de 15,08 (IC95% 8,43-26,97).
Conclusão:
O teste EN2 mostrou alta especificidade (89%)
e baixa sensibilidade (66%).
Palavras-chave:
câncer de próstata, biomarcador, EN2,
revisão sistemática, metanálise.
R
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