دورية أكاديمية
أعرض في EDS

Epigenetic Regulation of the Homeobox Gene MSX1 Associates with Platinum-Resistant Disease in High-Grade Serous Epithelial Ovarian Cancer.

التفاصيل البيبلوغرافية
العنوان: Epigenetic Regulation of the Homeobox Gene MSX1 Associates with Platinum-Resistant Disease in High-Grade Serous Epithelial Ovarian Cancer.
المؤلفون: Bonito NA; Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK., Borley J; Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK., Wilhelm-Benartzi CS; Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK., Ghaem-Maghami S; Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK., Brown R; Department of Surgery & Cancer, Imperial College London, London W12 0NN, UK.; Institute of Cancer Research, Sutton, London SM2 5NG, UK.
المصدر: Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2016 Jun 15; Vol. 22 (12), pp. 3097-3104. Date of Electronic Publication: 2016 Jan 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1557-3265 (Electronic) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Denville, NJ : The Association, c1995-
مواضيع طبية MeSH: Antineoplastic Agents/*therapeutic use , Biomarkers, Tumor/*genetics , Cisplatin/*therapeutic use , DNA Methylation/*genetics , Drug Resistance, Neoplasm/*genetics , MSX1 Transcription Factor/*genetics , Neoplasms, Glandular and Epithelial/*drug therapy , Neoplasms, Glandular and Epithelial/*genetics , Ovarian Neoplasms/*drug therapy , Ovarian Neoplasms/*genetics, Carcinoma, Ovarian Epithelial ; Cell Line, Tumor ; Cell Proliferation/genetics ; CpG Islands/genetics ; Cyclin-Dependent Kinase Inhibitor p21/biosynthesis ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Neoplasms, Glandular and Epithelial/mortality ; Ovarian Neoplasms/mortality ; RNA Interference ; RNA, Small Interfering/genetics
مستخلص: Purpose: Although high-grade serous ovarian cancer (HGSOC) is frequently chemoresponsive, a proportion of patients do not respond to platinum-based chemotherapy at presentation or have progression-free survival (PFS) of less than 6 months. Validated predictive biomarkers of lack of response would enable alternative treatment stratification for these patients and identify novel mechanisms of intrinsic resistance. Our aim was to identify DNA methylation biomarkers of poor response to chemotherapy and demonstrate involvement of the associated gene in platinum drug cell sensitivity.
Experimental Design: DNA methylation was investigated in independent tumor cohorts using Illumina HumanMethylation arrays and gene expression by Affymetrix arrays and qRT-PCR. The role of Msh homeobox 1 (MSX1) in drug sensitivity was investigated by gene reintroduction and siRNA knockdown of ovarian cancer cell lines.
Results: CpG sites at contiguous genomic locations within the MSX1 gene have significantly lower levels of methylation in independent cohorts of HGSOC patients, which recur by 6 months compared with after 12 months (P < 0.05, q < 0.05, n = 78), have poor RECIST response (P < 0.05, q < 0.05, n = 61), and are associated with PFS in an independent cohort (n = 146). A decrease in methylation at these CpG sites correlates with decreased MSX1 gene expression. MSX1 expression is associated with PFS (HR, 0.92; 95% CI, 0.85-0.99; P = 0.029; n = 309). Cisplatin-resistant ovarian cancer cell lines have reduced MSX1 expression, and MSX1 overexpression leads to cisplatin sensitization, increased apoptosis, and increased cisplatin-induced p21 expression.
Conclusions: Hypomethylation of CpG sites within the MSX1 gene is associated with resistant HGSOC disease at presentation and identifies expression of MSX1 as conferring platinum drug sensitivity. Clin Cancer Res; 22(12); 3097-104. ©2016 AACR.
(©2016 American Association for Cancer Research.)
References: Cancer Res. 1987 Jan 15;47(2):414-8. (PMID: 3539322)
J Clin Oncol. 1992 Apr;10(4):513-4. (PMID: 1548513)
Cancer Res. 2005 Feb 1;65(3):749-57. (PMID: 15705871)
Br J Cancer. 2012 Sep 25;107(7):1069-74. (PMID: 22935582)
Genes Dev. 1989 Jan;3(1):26-37. (PMID: 2565278)
Eur J Oral Sci. 2013 Oct;121(5):412-20. (PMID: 24028588)
Biochimie. 2012 Nov;94(11):2314-37. (PMID: 22847185)
EMBO Mol Med. 2014 Sep 11;6(10):1279-93. (PMID: 25214461)
Cancer Res. 1988 Nov 1;48(21):6166-72. (PMID: 3167863)
Cancer Res. 2005 Oct 1;65(19):8961-7. (PMID: 16204069)
Eur J Cancer. 2009 Jan;45(2):228-47. (PMID: 19097774)
Cancer Res. 1992 Aug 1;52(15):4196-9. (PMID: 1638534)
BJOG. 2010 Nov;117(12):1459-67. (PMID: 20560942)
Dev Cell. 2011 Sep 13;21(3):575-88. (PMID: 21852201)
Epigenetics. 2015;10(2):167-77. (PMID: 25587870)
Future Oncol. 2013 Dec;9(12 Suppl):19-23. (PMID: 24195526)
Mol Clin Oncol. 2014 Mar;2(2):212-218. (PMID: 24649335)
PLoS One. 2012;7(5):e37647. (PMID: 22629437)
J Pathol. 2010 May;221(1):49-56. (PMID: 20229506)
J Biol Chem. 2010 Mar 26;285(13):9636-41. (PMID: 20118233)
Cancer Manag Res. 2011;3:25-38. (PMID: 21734812)
J Mol Med (Berl). 2014 Aug;92(8):811-23. (PMID: 24996520)
Nat Rev Cancer. 2014 Nov;14(11):747-53. (PMID: 25253389)
معلومات مُعتمدة: 13086 United Kingdom CRUK_ Cancer Research UK; 15954 United Kingdom CRUK_ Cancer Research UK; A13086 United Kingdom CRUK_ Cancer Research UK
فهرسة مساهمة: Indexing Agency: NLM Local ID #: EMS66735 [Available on 12/15/16].
المشرفين على المادة: 0 (Antineoplastic Agents)
0 (Biomarkers, Tumor)
0 (Cyclin-Dependent Kinase Inhibitor p21)
0 (MSX1 Transcription Factor)
0 (MSX1 protein, human)
0 (RNA, Small Interfering)
Q20Q21Q62J (Cisplatin)
تواريخ الأحداث: Date Created: 20160115 Date Completed: 20180131 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC4849558
DOI: 10.1158/1078-0432.CCR-15-1669
PMID: 26763252
قاعدة البيانات: MEDLINE
الوصف
تدمد:1557-3265
DOI:10.1158/1078-0432.CCR-15-1669