دورية أكاديمية
Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome.
| العنوان: | Novel molecular subtypes of serous and endometrioid ovarian cancer linked to clinical outcome. |
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| المؤلفون: | Tothill RW; Peter MacCallum Cancer Center, University of Melbourne, Melbourne, Australia., Tinker AV, George J, Brown R, Fox SB, Lade S, Johnson DS, Trivett MK, Etemadmoghadam D, Locandro B, Traficante N, Fereday S, Hung JA, Chiew YE, Haviv I, Gertig D, DeFazio A, Bowtell DD |
| مؤلفون مشاركون: | Australian Ovarian Cancer Study Group |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2008 Aug 15; Vol. 14 (16), pp. 5198-208. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Print ISSN: 1078-0432 (Print) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Gene Expression Profiling*, Biomarkers, Tumor/*analysis , Ovarian Neoplasms/*genetics , Ovarian Neoplasms/*pathology, Adult ; Aged ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Lasers ; Microdissection ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; Ovarian Neoplasms/mortality ; Prognosis ; Tissue Array Analysis |
| مستخلص: | Purpose: The study aim to identify novel molecular subtypes of ovarian cancer by gene expression profiling with linkage to clinical and pathologic features. Experimental Design: Microarray gene expression profiling was done on 285 serous and endometrioid tumors of the ovary, peritoneum, and fallopian tube. K-means clustering was applied to identify robust molecular subtypes. Statistical analysis identified differentially expressed genes, pathways, and gene ontologies. Laser capture microdissection, pathology review, and immunohistochemistry validated the array-based findings. Patient survival within k-means groups was evaluated using Cox proportional hazards models. Class prediction validated k-means groups in an independent dataset. A semisupervised survival analysis of the array data was used to compare against unsupervised clustering results. Results: Optimal clustering of array data identified six molecular subtypes. Two subtypes represented predominantly serous low malignant potential and low-grade endometrioid subtypes, respectively. The remaining four subtypes represented higher grade and advanced stage cancers of serous and endometrioid morphology. A novel subtype of high-grade serous cancers reflected a mesenchymal cell type, characterized by overexpression of N-cadherin and P-cadherin and low expression of differentiation markers, including CA125 and MUC1. A poor prognosis subtype was defined by a reactive stroma gene expression signature, correlating with extensive desmoplasia in such samples. A similar poor prognosis signature could be found using a semisupervised analysis. Each subtype displayed distinct levels and patterns of immune cell infiltration. Class prediction identified similar subtypes in an independent ovarian dataset with similar prognostic trends. Conclusion: Gene expression profiling identified molecular subtypes of ovarian cancer of biological and clinical importance. |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) |
| تواريخ الأحداث: | Date Created: 20080814 Date Completed: 20080930 Latest Revision: 20220409 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1158/1078-0432.CCR-08-0196 |
| PMID: | 18698038 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1078-0432 |
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| DOI: | 10.1158/1078-0432.CCR-08-0196 |