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

ABSTRACT: 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, ?<0.001); low Per2 expression was correlated with poor differentiation (Per2: OR=2.41, 95%CI: 1.53?3.79, ?<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, ?=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, ?<0.001, ?2=4.2%; Per2: HR=1.62, 95%CI: 1.25?2.18, P<0.001, I2=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.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7241715 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Zhang Jiangguo J Lv Hong H Ji Mingzhu M Wang Zhimo Z Wu Wenqing W

PloS one 20200521 5

<h4>Background</h4>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.<h4>Methods</h ...[more]

PMID: 32437452

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Project description:BackgroundPim-1 is overexpressed in cancer tissues and plays a vital role in carcinogenesis. However, its clinical significance in cancers is not fully verified by meta-analysis, especially in relation to prognosis and clinicopathological features.MethodsFour databases, PubMed, Embase, Cochrane Library, and Web of Science, were searched. Literature screening and data extraction according to the inclusion and exclusion criteria. The quality of the included literatures was evaluated using the Newcastle-Ottawa scale and the data analysis was performed using STATA and Review Manager software.Results15 articles were finally included for meta-analysis, involving 1651 patients. Effect-size pooling analysis showed that high Pim-1 was related to poor overall survival (OS) (HR 1.68 [95% CI 1.17-2.40], P = .004) and disease-free survival (DFS) (HR 2.15 [95 %CI 1.15-4.01], P = .000). Subgroup analysis indicated that the detection techniques of Pim-1 were the main sources of heterogeneity, and 2 literatures using quantitative polymerase chain reaction (qPCR) for Pim-1mRNA had high homogeneity (I2 = .0%, P = .321) in OS. Another 13 studies that applied immunohistochemistry (IHC) for Pim-1 protein had significant heterogeneity (I2=82.2%, P = .000; I2=92%, P = .000) in OS and DFS, respectively, and further analysis demonstrated that ethnicity, sample size, and histopathological origin were considered to be the main factors affecting their heterogeneity. In addition, high Pim-1 was associated with lymph node metastasis (OR 1.40 [95% CI 1.02-1.92], P = .04), distant metastasis (OR 2.69 [95%CI 1.67-4.35], P < .0001), and clinical stage III-IV (OR .7 [95% CI .50-.96, P = .03). Sensitivity analysis suggested that the pooled results of each effect-size were stable and reliable, and there was no significant publication bias (P = .138) in all included articles.ConclusionHigh Pim-1 can not only predict poor OS and DFS of cancer, but also help to infer the malignant clinical characteristics of tumor metastasis. Pim-1 may be a potential and promising biomarker for early diagnosis, prognostic analysis and targeted therapy of tumors.

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

Publications

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

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