Cancer-specific alterations in nuclear matrix proteins determined by multi-omics analyses of ductal carcinoma in situ .

Autor:	Almutairy AF; Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, Saudi Arabia.; Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, United States.; AutoNation Institute for Breast Cancer Research and Care, Nova Southeastern University, Fort Lauderdale, FL, United States., Alhamed AS; Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, United States.; AutoNation Institute for Breast Cancer Research and Care, Nova Southeastern University, Fort Lauderdale, FL, United States.; Pharmacology Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia., Grant SG; AutoNation Institute for Breast Cancer Research and Care, Nova Southeastern University, Fort Lauderdale, FL, United States.; Department of Public Health, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, FL, United States.; Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States., Falso MJ; Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States., Day BW; Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, United States., Simmons CR; Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, United States.; AutoNation Institute for Breast Cancer Research and Care, Nova Southeastern University, Fort Lauderdale, FL, United States., Latimer JJ; Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, United States.; AutoNation Institute for Breast Cancer Research and Care, Nova Southeastern University, Fort Lauderdale, FL, United States.; Department of Obstetrics and Gynecology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in oncology [Front Oncol] 2024 Aug 06; Vol. 14, pp. 1406946. Date of Electronic Publication: 2024 Aug 06 (Print Publication: 2024).
DOI:	10.3389/fonc.2024.1406946
Abstrakt:	Introduction: Breast cancer (BC) is the most common cancer affecting women in the United States. Ductal carcinoma in situ (DCIS) is the earliest identifiable pre-invasive BC lesion. Estimates show that 14 to 50% of DCIS cases progress to invasive BC. Methods: Our objective was to identify nuclear matrix proteins (NMP) with specifically altered expression in DCIS and later stages of BC compared to non-diseased breast reduction mammoplasty and a contralateral breast explant culture using mass spectrometry and RNA sequencing to accurately identify aggressive DCIS. Results: Sixty NMPs were significantly differentially expressed between the DCIS and non-diseased breast epithelium in an isogenic contralateral pair of patient-derived extended explants. Ten of the sixty showed significant mRNA expression level differences that matched the protein expression. These 10 proteins were similarly expressed in non-diseased breast reduction cells. Three NMPs (RPL7A, RPL11, RPL31) were significantly upregulated in DCIS and all other BC stages compared to the matching contralateral breast culture and an unrelated non-diseased breast reduction culture. RNA sequencing analyses showed that these three genes were increasingly upregulated with BC progression. Finally, we identified three NMPs (AHNAK, CDC37 and DNAJB1) that were significantly downregulated in DCIS and all other BC stages compared to the isogenically matched contralateral culture and the non-diseased breast reduction culture using both proteomics and RNA sequencing techniques. Discussion: These genes should form the basis of, or contribute to, a molecular diagnostic panel that could identify DCIS lesions likely to be indolent and therefore not requiring aggressive treatment. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Almutairy, Alhamed, Grant, Falso, Day, Simmons and Latimer.)
Databáze:	MEDLINE
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