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Low circadian clock genes expression in cancers: A meta-analysis of its association with clinicopathological features and prognosis

BACKGROUND: Per1, Per2, Per3, Cry1, Cry2, Bmal1, Npas2 and CLOCK genes are the eight core circadian clock genes. Low expression of these circadian clock genes plays an important role in the progression of cancers. However, its clinicopathological and prognostic value in patients with cancers remains...

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Autores principales: Zhang, Jiangguo, Lv, Hong, Ji, Mingzhu, Wang, Zhimo, Wu, Wenqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241715/
https://www.ncbi.nlm.nih.gov/pubmed/32437452
http://dx.doi.org/10.1371/journal.pone.0233508
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author Zhang, Jiangguo
Lv, Hong
Ji, Mingzhu
Wang, Zhimo
Wu, Wenqing
author_facet Zhang, Jiangguo
Lv, Hong
Ji, Mingzhu
Wang, Zhimo
Wu, Wenqing
author_sort Zhang, Jiangguo
collection PubMed
description BACKGROUND: Per1, Per2, Per3, Cry1, Cry2, Bmal1, Npas2 and CLOCK genes are the eight core circadian clock genes. Low expression of these circadian clock genes plays an important role in the progression of cancers. However, its clinicopathological and prognostic value in patients with cancers remains controversial and inconclusive. We performed a meta-analysis of studies assessing the clinicopathological and prognostic significance of low expression of these genes in cancers. METHODS: Relevant studies were searched from the Cochrane Central Register of Controlled Trials, Embase, EBSCO, Ovid, PubMed, Science Direct, Wiley Online Library database, CNKI and Wan Fang database. The meta-analysis was performed by using STATA version 12 software. A random-effect model was employed to evaluate all pooled hazard ratios (HRs) and odd ratios (ORs). RESULTS: A total of 36 studies comprising 7476 cases met the inclusion criteria. Meta-analysis suggested that low expression of Per1 was associated with poor differentiation (Per1: OR=2.30, 95%CI: 1.36∼3.87, P=0.002) and deeper invasion depth (Per1: OR=2.12, 95%CI: 1.62∼2.77, Ρ<0.001); low Per2 expression was correlated with poor differentiation (Per2: OR=2.41, 95%CI: 1.53∼3.79, Ρ<0.001), worse TNM stage (Per2:OR=3.47, 95%CI: 1.88∼6.42, P<0.001) and further metastasis (Per2:OR=2.35, 95%CI: 1.35∼4.11, Ρ=0.003). Furthermore, the results revealed that low expressions of Per1 and Per2 were also correlated with poor overall survival of cancers (Per1: HR=1.35, 95%CI: 1.06∼1.72, P=0.014; Per2: HR=1.43, 95%CI: 1.10∼1.85, P=0.007). Subgroup analysis indicated that low Per1 and Per2 expressions were especially associated with poor prognosis of gastrointestinal caners (Per1: HR=1.33, 95%CI: 1.14∼1.55, Ρ<0.001, Ι(2)=4.2%; Per2: HR=1.62, 95%CI: 1.25∼2.18, P<0.001, I(2)=0.0%). CONCLUSIONS: Our study suggested that low Per1, Per2 and Npas2 expression played a distinct and crucial role in progression of cancers. Low expressions of Per1 and Per2 could serve as unfavorable indicators for cancers prognosis, especially for gastrointestinal cancers.
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spelling pubmed-72417152020-06-08 Low circadian clock genes expression in cancers: A meta-analysis of its association with clinicopathological features and prognosis Zhang, Jiangguo Lv, Hong Ji, Mingzhu Wang, Zhimo Wu, Wenqing PLoS One Research Article BACKGROUND: Per1, Per2, Per3, Cry1, Cry2, Bmal1, Npas2 and CLOCK genes are the eight core circadian clock genes. Low expression of these circadian clock genes plays an important role in the progression of cancers. However, its clinicopathological and prognostic value in patients with cancers remains controversial and inconclusive. We performed a meta-analysis of studies assessing the clinicopathological and prognostic significance of low expression of these genes in cancers. METHODS: Relevant studies were searched from the Cochrane Central Register of Controlled Trials, Embase, EBSCO, Ovid, PubMed, Science Direct, Wiley Online Library database, CNKI and Wan Fang database. The meta-analysis was performed by using STATA version 12 software. A random-effect model was employed to evaluate all pooled hazard ratios (HRs) and odd ratios (ORs). RESULTS: A total of 36 studies comprising 7476 cases met the inclusion criteria. Meta-analysis suggested that low expression of Per1 was associated with poor differentiation (Per1: OR=2.30, 95%CI: 1.36∼3.87, P=0.002) and deeper invasion depth (Per1: OR=2.12, 95%CI: 1.62∼2.77, Ρ<0.001); low Per2 expression was correlated with poor differentiation (Per2: OR=2.41, 95%CI: 1.53∼3.79, Ρ<0.001), worse TNM stage (Per2:OR=3.47, 95%CI: 1.88∼6.42, P<0.001) and further metastasis (Per2:OR=2.35, 95%CI: 1.35∼4.11, Ρ=0.003). Furthermore, the results revealed that low expressions of Per1 and Per2 were also correlated with poor overall survival of cancers (Per1: HR=1.35, 95%CI: 1.06∼1.72, P=0.014; Per2: HR=1.43, 95%CI: 1.10∼1.85, P=0.007). Subgroup analysis indicated that low Per1 and Per2 expressions were especially associated with poor prognosis of gastrointestinal caners (Per1: HR=1.33, 95%CI: 1.14∼1.55, Ρ<0.001, Ι(2)=4.2%; Per2: HR=1.62, 95%CI: 1.25∼2.18, P<0.001, I(2)=0.0%). CONCLUSIONS: Our study suggested that low Per1, Per2 and Npas2 expression played a distinct and crucial role in progression of cancers. Low expressions of Per1 and Per2 could serve as unfavorable indicators for cancers prognosis, especially for gastrointestinal cancers. Public Library of Science 2020-05-21 /pmc/articles/PMC7241715/ /pubmed/32437452 http://dx.doi.org/10.1371/journal.pone.0233508 Text en © 2020 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Jiangguo
Lv, Hong
Ji, Mingzhu
Wang, Zhimo
Wu, Wenqing
Low circadian clock genes expression in cancers: A meta-analysis of its association with clinicopathological features and prognosis
title Low circadian clock genes expression in cancers: A meta-analysis of its association with clinicopathological features and prognosis
title_full Low circadian clock genes expression in cancers: A meta-analysis of its association with clinicopathological features and prognosis
title_fullStr Low circadian clock genes expression in cancers: A meta-analysis of its association with clinicopathological features and prognosis
title_full_unstemmed Low circadian clock genes expression in cancers: A meta-analysis of its association with clinicopathological features and prognosis
title_short Low circadian clock genes expression in cancers: A meta-analysis of its association with clinicopathological features and prognosis
title_sort low circadian clock genes expression in cancers: a meta-analysis of its association with clinicopathological features and prognosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241715/
https://www.ncbi.nlm.nih.gov/pubmed/32437452
http://dx.doi.org/10.1371/journal.pone.0233508
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