膀胱癌 TERT 综合行为评估。

IF 2.4 3区医学 Q3 ONCOLOGY

Urologic Oncology-seminars and Original Investigations Pub Date : 2024-08-14 DOI:10.1016/j.urolonc.2024.06.024

Meryem El Azzouzi , Hajar El Ahanidi , Ilias Hassan , Mohammed Tetou , Ahmed Ameur , Mounia Bensaid , Abderrahmane Al Bouzidi , Mohamed Oukabli , Chaimae Hafidi Alaoui , Boutaina Addoum , Imane Chaoui , Laila Benbacer , Mohammed El Mzibri , Mohammed Attaleb

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引用次数: 0

摘要

背景：端粒酶活性在癌症的发生和发展中起着至关重要的作用。因此，通过端粒酶逆转录酶（TERT）启动子的突变和表观遗传学改变的相互作用来激活端粒酶，可以进一步揭示膀胱癌的诱发和进展：本研究选取了100例膀胱肿瘤组织，分析了四个分子特征：THOR甲基化状态、TERT启动子突变、端粒长度和TERT表达：在我们的研究中，88%的膀胱癌患者存在THOR区域的高甲基化，60%的患者存在TERT启动子区域的突变。在所有阶段和等级的膀胱癌中都能观察到 TERT 启动子甲基化。而TERT启动子突变则在晚期和分级中被检测到。在我们的队列中，非侵袭性膀胱癌病例中发现了高水平的TERT表达和长端粒，TERT表达与端粒长度之间存在显著关联。有趣的是，TERT表达量低的患者和端粒长的病例的无病生存期和总生存期明显更长：结论：TERT启动子中发生的甲基化和突变与膀胱癌的发生有关，可增加预后效果，并为端粒生物学在癌症中的应用提供新的见解。

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Comprehensive behavioural assessment of TERT in bladder cancer

Background

Telomerase activity plays a crucial role in cancer development and progression. Thus, telomerase activation through the interplay of mutations and epigenetic alterations in the telomerase reverse transcriptase (TERT) promoter may provide further insight into bladder cancer induction and progression.

Methods

In this study 100 bladder tumour tissues were selected, and four molecular signatures were analysed: THOR methylation status, TERT promotor mutation, telomere length, and TERT expression.

Results

In our study, 88% of bladder cancer patients had an hypermethylation of the THOR region and 60% had mutations in the TERT promoter region. TERT promoter methylation was observed in all stages and grades of bladder cancer. While, TERT promoter mutations were detected in advanced stages and grades. In our cohort, high levels of TERT expression and long telomeres have been found in noninvasive cases of bladder cancer, with a significant association between TERT expression and Telomere length. Interestingly, patients with low TERT expression and cases with long telomeres had significantly longer Disease-free survival and overall survival.

Conclusion

The methylation and mutations occurring in the TERT promoter are implicated in bladder carcinogenesis, offering added prognostic and supplying novel insight into telomere biology in cancer.

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来源期刊

Urologic Oncology-seminars and Original Investigations 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.70%

发文量

297

审稿时长

7.6 weeks

期刊介绍： Urologic Oncology: Seminars and Original Investigations is the official journal of the Society of Urologic Oncology. The journal publishes practical, timely, and relevant clinical and basic science research articles which address any aspect of urologic oncology. Each issue comprises original research, news and topics, survey articles providing short commentaries on other important articles in the urologic oncology literature, and reviews including an in-depth Seminar examining a specific clinical dilemma. The journal periodically publishes supplement issues devoted to areas of current interest to the urologic oncology community. Articles published are of interest to researchers and the clinicians involved in the practice of urologic oncology including urologists, oncologists, and radiologists.