دورية أكاديمية
أعرض في EDS

mRNA Expression and Methylation of the RAD51 , ATM , ATR , BRCA1 , and BRCA2 Genes in Gastric Adenocarcinoma.

التفاصيل البيبلوغرافية
العنوان: mRNA Expression and Methylation of the RAD51 , ATM , ATR , BRCA1 , and BRCA2 Genes in Gastric Adenocarcinoma.
المؤلفون: Pádua JDB; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil., Mariano CFA; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil., Fabro AT; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil., Lizarte Neto FS; Department of Surgery and Anatomy, Ribeirão Preto Medical School, USP, Ribeirão Preto, SP, Brazil., Zuliani RL; Department of Surgery and Anatomy, Ribeirão Preto Medical School, USP, Ribeirão Preto, SP, Brazil., Sares CTG; Department of Surgery and Anatomy, Ribeirão Preto Medical School, USP, Ribeirão Preto, SP, Brazil., Dos Santos JS; Department of Surgery and Anatomy, Ribeirão Preto Medical School, USP, Ribeirão Preto, SP, Brazil., Sankarankutty AK; Department of Surgery and Anatomy, Ribeirão Preto Medical School, USP, Ribeirão Preto, SP, Brazil., Tirapelli DPDC; Department of Surgery and Anatomy, Ribeirão Preto Medical School, USP, Ribeirão Preto, SP, Brazil., Silveira VDS; Department of Genetics, Ribeirão Preto Medical School, USP, Ribeirão Preto, SP, Brazil., de Molfetta GA; Department of Genetics, Ribeirão Preto Medical School, USP, Ribeirão Preto, SP, Brazil., Júnior WADS; Department of Genetics, Ribeirão Preto Medical School, USP, Ribeirão Preto, SP, Brazil., Brunaldi MO; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil.
المصدر: Biomarker insights [Biomark Insights] 2024 Jan 29; Vol. 19, pp. 11772719231225206. Date of Electronic Publication: 2024 Jan 29 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: SAGE Publications Country of Publication: United States NLM ID: 101288638 Publication Model: eCollection Cited Medium: Print ISSN: 1177-2719 (Print) Linking ISSN: 11772719 NLM ISO Abbreviation: Biomark Insights Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: <2016- > : Thousand Oaks, CA : SAGE Publications
Original Publication: Auckland, N.Z. : Libertas Academica Ltd.
مستخلص: Background: Immunohistochemical prognostic significance of the homologous recombination-related proteins RAD51, ATM, BRCA1, and BRCA2 is known in gastric adenocarcinoma, one of the deadliest cancers.
Objective and Design: This retrospective cohort study aimed to evaluate mRNA expression and promoter methylation of some homologous recombination-related genes in this neoplasm.
Methods: We evaluated mRNA expression and methylation of RAD51 , ATM , ATR , BRCA1 , and BRCA2 in tumor and non-tumor frozen samples from gastrectomy specimens by RT-qPCR and MS-HRM, correlating our results with previous immunohistochemistry data and prognostic features.
Results: RAD51 , ATR , BRCA1 , BRCA2 , and ATM mRNA expression was detected in 93.75% (45/48), 93.75% (45/48), 91.67% (44/48), 83.33% (40/48), and 89.58% (43/48) of the tumors; partial or complete methylation, in 94.87% (37/39), 0 (0/42), 97.56% (40/41), 100% (41/41), and 0 (0/40), respectively. Most gene pairs showed significant weak to moderate positive correlations of tumoral mRNA expression with each other: RAD51 with ATR ( P  = .027), BRCA1 ( P  < .001), and BRCA2 ( P  < .001); ATR with BRCA1 ( P  = .007), and ATM ( P  = .001); BRCA1 with BRCA2 ( P  = 0.001). BRCA1 mRNA was reduced in tumors compared with non-neoplastic mucosa (0.345 vs 1.272, P  = .015) and, excluding neoadjuvant therapy cases, in T3 to T4 tumors compared with T2 (0.414 vs 0.954, P  = .035). Greater tumoral RAD51 mRNA levels correlated with perineural invasion (1.822 vs 0.725, P  = .010) and death (1.664 vs 0.929, P  = .036), but not with survival time. There was an inverse association between nuclear immunohistochemical positivity for ATR and its mRNA levels (0.487 vs 0.907, P  = .032), and no significant correlation for the other markers.
Conclusions: Our results suggest RAD51 , BRCA1 , and BRCA2 methylation as a frequent epigenetic mechanism in gastric cancer, support the hypothesis that reduced BRCA1 expression participates in disease progression, and show an association between RAD51 mRNA and perineural invasion and mortality that may be considered unexpected, considering the former immunohistochemical studies. The lack of correlation between immunohistochemistry and mRNA, and even the inverse association, for ATR , can be seen as indicative of action of post-transcriptional or post-translational regulatory mechanisms, to be better investigated.
Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
(© The Author(s) 2024.)
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فهرسة مساهمة: Keywords: DNA repair; Stomach neoplasms; homologous recombination; mRNA; methylation
تواريخ الأحداث: Date Created: 20240131 Latest Revision: 20240201
رمز التحديث: 20240201
مُعرف محوري في PubMed: PMC10826385
DOI: 10.1177/11772719231225206
PMID: 38293680
قاعدة البيانات: MEDLINE
الوصف
تدمد:1177-2719
DOI:10.1177/11772719231225206