Diagnostic Value of Methylated Human Telomerase Reverse Transcriptase in Human Cancers: A Meta-Analysis.

Wei Gao,Yuan Shi,Josh Chia-Ching Wu,Wei Liu,Wei-Yin Lin,Thian-Sze Wong,Jimmy Yu-Wai Chan

doi:10.3389/fonc.2015.00296

Abstract

Human telomerase reverse transcriptase (hTERT) plays a critical role in the pathogenesis of human malignancies. Overexpression of hTERT is essential in controlling the propagation of cancer cells. The CpG island located at hTERT promoter region is subjected to methylation modification in human cancer. In this perspective article, we discussed the diagnostic value of methylated hTERT in human cancers. The definitive diagnosis of most solid tumors is based on histological and immunohistochemical features. Under certain circumstances, however, the use of methylated hTERT might be useful in overcoming the limitation of the conventional methods. Methylated hTERT showed a good diagnostic power in discriminating cancer from benign or normal tissues. Nevertheless, differences in detection method, methylation site, cancer type, and histological subtype of cancer make it difficult to evaluate the actual diagnostic accuracy of methylated hTERT. Therefore, we performed subgroup analysis to assess the effects of these factors on the diagnostic efficiency of methylated hTERT. We demonstrated that quantitative MSP (qMSP) assay offers the highest discriminative power between normal and cancer in comparison with different detection methods. In addition, the methylated sites selected by different studies had an impact on the detection performance. Moreover, the diagnostic power of methylated hTERT was affected by cancer type and histological subtype. In conclusion, the existing evidence demonstrated that methylated hTERT is effective in cancer detection. Detailed profiling of the methylation sites to local the common methylation hotspot across human cancers is warranted to maximize the diagnostic value of methylated hTERT in cancer detection.

Highlights

Cancer is a leading cause of death, accounting for about 14.6% of all human deaths [1]
Increased Human telomerase reverse transcriptase (hTERT) transcript level is an indication of cancer cells and reflects the proliferative propensity
High hTERT level in the cancerous tissue is associated with the poor outcome in a number of human cancers [5,6,7,8]

Summary

INTRODUCTION

Cancer is a leading cause of death, accounting for about 14.6% of all human deaths [1]. For the diagnostic performance of methylated hTERT in discriminating cancer from benign tissue, the pooled sensitivity and specificity were 0.57 (95% CI, 0.49–0.65) and 0.81 (95% CI, 0.75–0.86), respectively AUC from studies using qMSP assay (0.97) was obviously higher in comparison with the non-qMSP studies (range: 0.58–0.85) (Table 1) These results indicated that different detection methods affected the diagnostic efficiency of methylated hTERT. Among the 10 included studies, only Wang et al [27] provided histological information for subsequent subgroup analysis Their lung cancer cohorts could be stratified into two groups: adenocarcinoma and squamous cell carcinoma of which, methylated hTERT had a remarkably higher value in sensitivity, DOR, and AUC in lung squamous cell carcinoma in comparison with adenocarcinoma (Table 1)

CONCLUSION

Findings

Detection methods qMSP