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Supplementary Tables from Pooled Clustering of High-Grade Serous Ovarian Cancer Gene Expression Leads to Novel Consensus Subtypes Associated with Survival and Surgical Outcomes

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posted on 2023-03-31, 20:20 authored by Chen Wang, Sebastian M. Armasu, Kimberly R. Kalli, Matthew J. Maurer, Ethan P. Heinzen, Gary L. Keeney, William A. Cliby, Ann L. Oberg, Scott H. Kaufmann, Ellen L. Goode

Supplementary Table 1. Key clinical characteristics of public cohort with respect to individual 14 studies Supplementary Table 2. Key clinical characteristics of Mayo Clinic HGSOC cohort Supplementary Table 3. Expression centroids of five de novo subtypes Supplementary Table 4. Expression centroids of four Tothill's HGSOC subtypes (C1/C2/C4/C5) Supplementary Table 5. Cross-tab between de novo subtypes and two other subtyping systems in public cohort Supplementary Table 6. The differential expression analysis results between s1.MES and rest de novo subtypes in public cohort Supplementary Table 7. The differential expression analysis results between s2.IMM and rest de novo subtypes in public cohort Supplementary Table 8. The differential expression analysis results between s3.RPO and rest de novo subtypes in public cohort Supplementary Table 9. The differential expression analysis results between s4.DIF and rest de novo subtypes in public cohort Supplementary Table 10. The differential expression analysis results between s5.ANM and rest de novo subtypes in public cohort Supplementary Table 11. Distribution tables of HGSOC molecular subtypes vs. surgical outcomes (optimal- and sub-optimal debulking) in Public and Mayo Clinic cohorts Supplementary Table 12. Previously reported debulking-predictive genes and their differential expressions related to s1.MES subtype in HGSOC public cases Supplementary Table 13. Enriched pathways (q-value <=0.1) for s1.MES vs. rest de novo subtypes comparisons Supplementary Table 14. Enriched pathways (q-value <=0.1) for s2.IMM vs. rest de novo subtypes comparisons Supplementary Table 15. Enriched pathways (q-value <=0.1) for s3.PRO vs. rest de novo subtypes comparisons Supplementary Table 16. Enriched pathways (q-value <=0.1) for s4.DIF vs. rest de novo subtypes comparisons Supplementary Table 17. Enriched pathways (q-value <=0.1) for s5.ANM vs. rest de novo subtypes comparisons Supplementary Table 18. Distributions of BRCAness status versus de novo subtypes for TCGA cases with mutation and methylation calls: "mBRCA" indicates cases with germline or somatic deleterious mutations in BRCA1/2; "meth.BRCA1" indicates cases with BRCA1 promoter methylation; "wtBRCA" indicates cases without known BRCA1/2 mutations or promoter methylations.

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Mayo Clinic

National Cancer Institute

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ARTICLE ABSTRACT

Purpose: Here we assess whether molecular subtyping identifies biological features of tumors that correlate with survival and surgical outcomes of high-grade serous ovarian cancer (HGSOC).Experimental Design: Consensus clustering of pooled mRNA expression data from over 2,000 HGSOC cases was used to define molecular subtypes of HGSOCs. This de novo classification scheme was then applied to 381 Mayo Clinic HGSOC patients with detailed survival and surgical outcome information.Results: Five molecular subtypes of HGSOC were identified. In the pooled dataset, three subtypes were largely concordant with prior studies describing proliferative, mesenchymal, and immunoreactive tumors (concordance > 70%), and the group of tumors previously described as differentiated type was segregated into two new types, one of which (anti-mesenchymal) had downregulation of genes that were typically upregulated in the mesenchymal subtype. Molecular subtypes were significantly associated with overall survival (P < 0.001) and with rate of optimal surgical debulking (≤1 cm, P = 1.9E−4) in the pooled dataset. Among stage III-C or IV Mayo Clinic patients, molecular subtypes were also significantly associated with overall survival (P = 0.001), as well as rate of complete surgical debulking (no residual disease; 16% in mesenchymal tumors compared with >28% in other subtypes; P = 0.02).Conclusions: HGSOC tumors may be categorized into five molecular subtypes that associate with overall survival and the extent of residual disease following debulking surgery. Because mesenchymal tumors may have features that were associated with less favorable surgical outcome, molecular subtyping may have future utility in guiding neoadjuvant treatment decisions for women with HGSOC. Clin Cancer Res; 23(15); 4077–85. ©2017 AACR.

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