Analysis of TERT mRNA Levels and Clinicopathological Features in Patients with Peritoneal Mesothelioma.

IF 4.4 2区医学 Q1 ONCOLOGY Cancers Pub Date : 2025-01-14 DOI:10.3390/cancers17020252

Antonio d'Amati, Gabriella Serio, Andrea Quaranta, Luigi Vimercati, Michelina De Giorgis, Loredana Lorusso, Mariella Errede, Vito Longo, Andrea Marzullo, Domenico Ribatti, Tiziana Annese

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Abstract

Background/objectives: Telomerase reverse transcriptase (TERT) is the catalytic subunit of the telomerase enzyme responsible for telomere length maintenance and is an important cancer hallmark. Our study aimed to clarify the mRNA expression of TERT in peritoneal mesothelioma (PeM), and to explore the relationship between its expression and the clinicopathological parameters and prognosis of patients with PeM.

Methods: In a cohort of 13 MpeM patients, we evaluated histotype, nuclear grade, mitotic count, necrosis, inflammation, Ki67, BAP1, MTAP and p16 expression by immunohistochemistry, p16/CDKN2A status by FISH and TERT mRNA expression by RNAscope.

Results: Our results showed several statistical correlations between TERT mRNA-score and other investigated features: (i) a poor positive correlation with BAP1 score (r = 0.06340; p ≤ 0.0001); (ii) a moderate positive correlation with p16 FISH del homo (r = 0.6340; p ≤ 0.0001); (iii) a fair negative correlation with p16 FISH del hetero (r = -0.3965; p ≤ 0.0001); a negative poor correlation with MTAP (r = -0.2443; p ≤ 0.0001); and (iv) a negative fair correlation with inflammatory infiltrate (r = -0.5407; p = 0.0233). Moreover, patients survive for a significantly longer time if they have a low mitotic index adjusted (2-4 mitotic figures per 2 mm²) (p ≤ 0.0001), are male (p = 0.0152), lose BAP1 (p = 0.0152), are p16 positive and present no deletion or heterozygous for p16 (p ≤ 0.01).

Conclusions: TERT is highly expressed in PeM, but it is not one of the crucial factors in evaluating the prognosis of patients. Nevertheless, the results validate the prognostic significance of the mitotic index, BAP1 loss and p16/CDKN2A status.

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腹膜间皮瘤患者的 TERT mRNA 水平和临床病理特征分析

背景/目的：端粒酶逆转录酶（TERT）是端粒酶的催化亚基，负责端粒长度的维持，是一个重要的癌症标志。本研究旨在明确TERT mRNA在腹膜间皮瘤（PeM）中的表达情况，并探讨其表达与PeM患者临床病理参数及预后的关系。方法：在13例MpeM患者队列中，我们通过免疫组织化学评估组织类型，核分级，有丝分裂计数，坏死，炎症，Ki67, BAP1， MTAP和p16表达，FISH评估p16/CDKN2A状态，RNAscope评估TERT mRNA表达。结果：我们的研究结果显示，TERT mrna评分与其他研究特征之间存在统计学相关性：(i)与BAP1评分呈正相关(r = 0.06340；P≤0.0001)；（ii）与p16 FISH del homo呈正相关(r = 0.6340；P≤0.0001)；（iii）与p16 FISH del hetero呈负相关（r = -0.3965）；P≤0.0001)；与MTAP呈负相关（r = -0.2443）；P≤0.0001)；（iv）与炎症浸润呈负相关(r = -0.5407；P = 0.0233)。此外，如果有丝分裂指数调整后较低（每2平方毫米2-4个有丝分裂数）（p≤0.0001），男性（p = 0.0152）， BAP1缺失（p = 0.0152）， p16阳性，p16无缺失或杂合（p≤0.01），患者存活时间明显延长。结论：TERT在PeM中高表达，但并不是评价患者预后的关键因素之一。然而，结果验证了有丝分裂指数、BAP1缺失和p16/CDKN2A状态的预后意义。

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来源期刊

Cancers Medicine-Oncology

CiteScore

8.00

自引率

9.60%

发文量

5371

审稿时长

18.07 days

期刊介绍： Cancers (ISSN 2072-6694) is an international, peer-reviewed open access journal on oncology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.