Telomere shortening and PCDH10 promoter methylation in colorectal cancer mucosae

Background: telomerase activity and telomere length (TL) have important implications in several human diseases.Telomere shortening is associated with colorectal carcinogenesis. Recent studies also showed that protocadherin 10(PCDH10) plays a critical role in cancer cell growth, by negatively regulating telomerase activity. PCDH10isfrequently downregulated by promoter DNA methylation. The aim of this study was to investigate whether PCDH10promoter methylation was associated with TL in colorectal cancer (CRC). Methods: DNA was extracted from 35 CRC and 35 adjacent normal tissues with Gentra Purgene Kit (Qiagen, Hilden,Germany). A quantitative methylation-specific PCR (MSP) based method was used to analyze a selected CpG site inPCDH10promoter. TL was evaluated with qPCR and expressed as telomere to single copy gene (T/S) ratio.Differences were assessed with Mann-Whitney test or Wilcoxon signed-ranks test when appropriate, whilstcorrelation analyses were performed with Spearman’s test. Diagnostic performance was calculated with receiveroperating characteristics (ROC) curve analysis. The level of statistical significance was set at p <0.05. Results: we found that TL was significantly lower in CRC than in adjacent non-cancerous tissues (p=0.0005). Thearea under the ROC curve (AUC) for TL was 0.759 (95% Confidence Interval: 0.643-0.875, p=0.0002). AberrantPCDH10promoter methylation was detected in 100% of CRC tissues but in none of paired non-cancerous tissues.The median methylation rate in CRC tissues was 55.7% (range: 6.1-97.8%). TL was negatively correlated withPCDH10promoter methylation (r=-0.42, p=0.0002). Conclusions: these results suggest a pivotal role of telomere shortening and PCDH10methylation in CRC tissues.TL may be seen as a potential biomarker in CRC diagnostics.