Prognostic Significance of Cyclin D1 Expression in Colorectal Cancer: A Meta-Analysis of Observational Studies

<div><p>Objective</p><p>Cyclin D1 plays a vital role in cancer cell cycle progression and is overexpressed in many human cancers, including colorectal cancer (CRC). However, the prognostic value of cyclin D1 overexpression in colorectal cancer is conflicting and heterogeneous. We conducted a meta-analysis to more precisely evaluate its prognostic significance.</p><p>Methods</p><p>A comprehensive literature search for relevant studies published up to January 2014 was performed using PubMed, EMBASE, and ISI Web of Science. The pooled hazard ratio (HR) with 95% confidence intervals (CI) was used to estimate the effects.</p><p>Results</p><p>22 studies with 4150 CRC patients were selected to evaluate the association between cyclin D1 and overall survival (OS), disease-free survival (DFS) and clinicopathological parameters. In a random-effects model, the results showed that cyclin D1 overexpression in CRC was significantly associated with both poor OS (HR = 0.73, 95% CI: 0.63–0.85, <i>P</i><0.001) and DFS (HR = 0.60, 95% CI: 0.44–0.82, <i>P</i> = 0.001). Additionally, cyclin D1 overexpression was significantly associated with more relative older patients (≥60 years) (OR 0.62, 95% CI 0.44–0.89, <i>P</i> = 0.009), T3,4 tumor invasion (OR 0.70, 95% CI 0.57–0.85, <i>P</i><0.001), N positive (OR 0.75, 95% CI 0.60–0.95, <i>P</i> = 0.016) and distant metastasis (OR 0.60, 95% CI 0.36–0.99, <i>P</i> = 0.047) of CRC.</p><p>Conclusion</p><p>The meta-analysis results indicated that cyclin D1 is an unfavorable prognostic factor for CRC. Cyclin D1 overexpression might be associated with poor clinical outcome and some clinicopathological factors such as age, T category, N category and distant metastasis in CRC patients.</p></div

Forest plot of the hazard ratio (HR) for the association of cyclin D1 expression with disease-free survival (DFS).

<p>Forest plot of the hazard ratio (HR) for the association of cyclin D1 expression with disease-free survival (DFS).</p

Begg's funnel plot for the evaluation of potential publication bias on overall estimate of overall survival (OS).

<p>Begg's funnel plot for the evaluation of potential publication bias on overall estimate of overall survival (OS).</p

Results of overall and subgroup analyses for effects of cyclin D1 expression on overall and disease-free survival in colorectal cancer.

<p>Abbreviations: HR: hazard ratio; 95% CI: 95% confidence interval; N: number of studies.</p

Sensitivity analysis based on stepwise omitting one study at a time for disease-free survival (DFS).

<p>Sensitivity analysis based on stepwise omitting one study at a time for disease-free survival (DFS).</p

Flow diagram of screened, excluded, and analyzed publications.

<p>Flow diagram of screened, excluded, and analyzed publications.</p

Sensitivity analysis based on stepwise omitting one study at a time for overall survival (OS).

<p>Sensitivity analysis based on stepwise omitting one study at a time for overall survival (OS).</p

Characteristics of studies included in the meta-analysis.

<p>*these studies looked back at medical records and did not report the time of follow-up.</p><p>Abbreviations: BMI: body mass index; CA19-9: carbohydrate antigen 19-9; CEA: carcinoembryonic antigen; CIMP: the CpG island methylator phenotype; CK-19: cytokeratin-19; COX-2: cyclooxygenase-2; CRC: colorectal cancer; DFS, disease-free survival; FASN: fatty acid synthase; HR: hazard ratio; LINE-1: long interspersed nucleotide element-1; MMP-7: matrix metalloproteinase-7; MSI: microsatellite instability; NA: not available; OS: overall survival; pRb: retinoblastoma protein; PRL: prolactin; P-Stat5: phosphorylated signal transducer and activator of transcription-5; VEGF: vascular endothelial growth factor; YAP: Yes-associated protein.</p

Meta-analysis of the association between cyclin D1 expression and clinicopathological features of colorectal cancer.

<p>Abbreviations: OR: odds ratio; 95% CI: 95% confidence interval; mod: moderate; por: poor; N, number of studies.</p

Begg's funnel plot for the evaluation of potential publication bias on overall estimate of disease-free survival (DFS).

<p>Begg's funnel plot for the evaluation of potential publication bias on overall estimate of disease-free survival (DFS).</p