Gao Wei, Shi Yuan, Liu Wei, Lin Wei-Yin, Wu Josh Chia-Ching, Chan Jimmy Yu-Wai, Wong Thian-Sze
Department of Surgery, The University of Hong Kong , Hong Kong , China.
Department of Plastic and Reconstructive Surgery, Shanghai Jiaotong University School of Medicine , Shanghai , China.
Front Oncol. 2015 Dec 24;5:296. doi: 10.3389/fonc.2015.00296. eCollection 2015.
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.
人端粒酶逆转录酶(hTERT)在人类恶性肿瘤的发病机制中起着关键作用。hTERT的过表达对于控制癌细胞的增殖至关重要。位于hTERT启动子区域的CpG岛在人类癌症中会发生甲基化修饰。在这篇观点文章中,我们讨论了甲基化hTERT在人类癌症中的诊断价值。大多数实体瘤的明确诊断基于组织学和免疫组化特征。然而,在某些情况下,使用甲基化hTERT可能有助于克服传统方法的局限性。甲基化hTERT在区分癌症与良性或正常组织方面显示出良好的诊断能力。尽管如此,检测方法、甲基化位点、癌症类型和癌症组织学亚型的差异使得难以评估甲基化hTERT的实际诊断准确性。因此,我们进行了亚组分析,以评估这些因素对甲基化hTERT诊断效率的影响。我们证明,与不同检测方法相比,定量甲基化特异性PCR(qMSP)检测在区分正常组织和癌组织方面具有最高的鉴别能力。此外,不同研究选择的甲基化位点对检测性能有影响。而且,甲基化hTERT的诊断能力受癌症类型和组织学亚型的影响。总之,现有证据表明甲基化hTERT在癌症检测中是有效的。有必要详细分析甲基化位点,以定位人类癌症中常见的甲基化热点,从而最大限度地提高甲基化hTERT在癌症检测中的诊断价值。