ABSTRACT
Recently, microRNAs (miRNAs) have been shown to be involved in multiple biological pathways that can influence tumor progression and metastasis and they can serve as prognostic biomarkers in many cancers. The present study examined the prognostic significance of miR-215 in cervical cancer. The paraffin-embedded paired cervical scrape samples and tumor tissue samples from 302 patients with stage II cervical cancer were detected for the expression of miR-215 by using qRT-PCR. A miR-215-based classifier was established by using the Cox regression model. The prognostic and predictive accuracy of this classifier was determined in both the internal testing group of 138 patients, and the external independent group of 280 patients. Moreover, cervical cancer HeLa cells overexpressing miR-215 (HeLa-miR-215) were constructed and subcutaneously injected into the nude mice to examine the effect of miR-215 on tumor growth and metastasis in vivo. The results showed that the expression level of miR-215 was significantly higher in cervical cancer tissues than in paired normal tissues (P<0.0001). When patients were classified into high- and low-risk cancer progression groups according to miR-215 level, the 5-year disease-free survival in high- and low-risk groups were 43% (95% CI: 32.1-51.6) and 67% (95% CI: 48.6-77.3) (hazard ratio [HR] 2.02, 95% CI: 1.16-3.52; P=0.013) respectively. Moreover, the expression level of miR-215 was negatively associated with survival rate in patients at TNM stage T3 (HR: 3.317; 95% CI: 1.18-5.14, P=0.017) and TNM stage T4 (HR: 3.48; 95% CI: 1.49-4.45, P=0.008). Tumor volume in nude mice injected with HeLa-miR-215 cells was significantly larger than that in mice injected with control HeLa cells. It was concluded that the expression level of miR-215 is associated with cervical tumor progression and worse survival rate, suggesting that it may serve as a potential prognostic marker to identify patients at higher risk of recurrence.
Subject(s)
Aged , Animals , Female , Humans , Male , Mice , Middle Aged , Biomarkers, Tumor , Genetics , Disease-Free Survival , Gene Expression Regulation, Neoplastic , HeLa Cells , MicroRNAs , Genetics , Neoplasm Staging , Prognosis , Uterine Cervical Neoplasms , Genetics , PathologyABSTRACT
Recently, microRNAs (miRNAs) have been shown to be involved in multiple biological pathways that can influence tumor progression and metastasis and they can serve as prognostic biomarkers in many cancers. The present study examined the prognostic significance of miR-215 in cervical cancer. The paraffin-embedded paired cervical scrape samples and tumor tissue samples from 302 patients with stage II cervical cancer were detected for the expression of miR-215 by using qRT-PCR. A miR-215-based classifier was established by using the Cox regression model. The prognostic and predictive accuracy of this classifier was determined in both the internal testing group of 138 patients, and the external independent group of 280 patients. Moreover, cervical cancer HeLa cells overexpressing miR-215 (HeLa-miR-215) were constructed and subcutaneously injected into the nude mice to examine the effect of miR-215 on tumor growth and metastasis in vivo. The results showed that the expression level of miR-215 was significantly higher in cervical cancer tissues than in paired normal tissues (P<0.0001). When patients were classified into high- and low-risk cancer progression groups according to miR-215 level, the 5-year disease-free survival in high- and low-risk groups were 43% (95% CI: 32.1-51.6) and 67% (95% CI: 48.6-77.3) (hazard ratio [HR] 2.02, 95% CI: 1.16-3.52; P=0.013) respectively. Moreover, the expression level of miR-215 was negatively associated with survival rate in patients at TNM stage T3 (HR: 3.317; 95% CI: 1.18-5.14, P=0.017) and TNM stage T4 (HR: 3.48; 95% CI: 1.49-4.45, P=0.008). Tumor volume in nude mice injected with HeLa-miR-215 cells was significantly larger than that in mice injected with control HeLa cells. It was concluded that the expression level of miR-215 is associated with cervical tumor progression and worse survival rate, suggesting that it may serve as a potential prognostic marker to identify patients at higher risk of recurrence.
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the association between single nucleotide polymorphisms (SNPs) of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene and susceptibility to cervical cancer.</p><p><b>METHODS</b>One hundred patients and 100 healthy controls from Hubei province were genotyped for 20 polymorphic loci using Sequenom.</p><p><b>RESULTS</b>The frequency of rs11571316 G allele and rs5742909 T allele, which are localized in the promoter region, and rs11571319 A allele, which is downstream of the gene, were significantly higher in patients than in controls. Luciferase assay showed that, as the previously reported rs5742909 T allele, rs11571316 G allele could significantly increase the expression of the reporter gene.</p><p><b>CONCLUSION</b>SNPs in the promoter region of (CTLA4) gene might increase the susceptibility to cervical cancer by increasing (CTLA4) gene expression.</p>