Molecular Subtypes of Uterine Leiomyosarcoma and Correlation with Clinical Outcome
| Autor: | Karin K. Shih, Li-Xuan Qin, Martee L. Hensley, Mario M. Leitao, Narciso Olvera, Qin C. Zhou, William D. Tap, Maria Bisogna, Douglas A. Levine, Nikolaus Schultz, Gary K. Schwartz, Joyce N. Barlin, Jeff Boyd, Anders Jacobsen |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Oncology
Leiomyosarcoma Adult Cancer Research medicine.medical_specialty FDR false discovery rate LMS leiomyosarcoma education FFPE formalin-fixed and paraffin-embedded Bioinformatics lcsh:RC254-282 Article OS overall survival 03 medical and health sciences 0302 clinical medicine GSEA gene set enrichment analysis Internal medicine medicine Humans Progression-free survival Gene NL normal myometrium 030304 developmental biology Aged Aged 80 and over 0303 health sciences business.industry Microarray analysis techniques Gene Expression Profiling Cell cycle Middle Aged medicine.disease Microarray Analysis MSKCC Memorial Sloan Kettering Cancer Center ULMS uterine leiomyosarcoma lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell Cycle Gene PFS progression-free survival 3. Good health Neoplasm Proteins Gene expression profiling Genes cdc 030220 oncology & carcinogenesis Uterine Neoplasms Female DNA microarray business |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 17, Iss 2, Pp 183-189 (2015) Neoplasia (New York, N.Y.) |
| ISSN: | 1522-8002 1476-5586 |
| Popis: | The molecular etiology of uterine leiomyosarcoma (ULMS) is poorly understood, which accounts for the wide disparity in outcomes among women with this disease. We examined and compared the molecular profiles of ULMS and normal myometrium (NL) to identify clinically relevant molecular subtypes. Discovery cases included 29 NL and 23 ULMS specimens. RNA was hybridized to Affymetrix U133A 2.0 transcription microarrays. Differentially expressed genes and pathways were identified using standard methods. Fourteen NL and 44 ULMS independent archival samples were used for external validation. Molecular subgroups were correlated with clinical outcome. Pathway analyses of differentially expressed genes between ULMS and NL samples identified overrepresentation of cell cycle regulation, DNA repair, and genomic integrity. External validation confirmed differential expression in 31 genes (P < 4.4 × 10−4, Bonferroni corrected), with 84% of the overexpressed genes, including CDC7, CDC20, GTSE1, CCNA2, CCNB1, and CCNB2, participating in cell cycle regulation. Unsupervised clustering of ULMS identified two clades that were reproducibly associated with progression-free (median, 4.0 vs 26.0 months; P = .02; HR, 0.33) and overall (median, 18.2 vs 77.2 months; P = .04; HR, 0.33) survival. Cell cycle genes play a key role in ULMS sarcomagenesis, providing opportunities for therapeutic targeting. Reproducible molecular subtypes associated with clinical outcome may permit individualized adjuvant treatment after clinical trial validation. |
| Databáze: | OpenAIRE |
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