Details

Autor(en) / Beteiligte

• Dubil, Elizabeth A.
• Tian, Chunqiao
• Wang, Guisong
• Tarney, Christopher M.
• Bateman, Nicholas W.
• Levine, Douglas A.
• Conrads, Thomas P.
• Hamilton, Chad A.
• Maxwell, George Larry
• Darcy, Kathleen M.

Titel

Racial disparities in molecular subtypes of endometrial cancer

Ist Teil von

• Gynecologic oncology, 2018-04, Vol.149 (1), p.106-116

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Racial differences in the molecular subtypes of endometrial cancer and associations with progression-free survival (PFS) were evaluated. Molecular, clinical and PFS data were acquired from the Cancer Genome Atlas (TCGA) including classification into the integrative, somatic copy number alteration and transcript-based subtypes. The prevalence and prognostic value of the aggressive molecular subtypes (copy number variant [CNV]-high, cluster 4 or mitotic) were evaluated in Black and White patients. There were 337 patients including 14% self-designated as Black, 27% with advanced stage, and 82% with endometrioid histology. The CNV-high subtype was more common in Black than White patients (61.9% vs. 23.5%, P=0.0005) and suggested worse PFS in Black patients (hazard ratio [HR]=3.4, P=0.189). The cluster 4 subtype was more prevalent in Black patients (56.8% vs. 20.9%, P<0.0001) and associated with worse PFS in Black patients (HR=3.4, P=0.049). The mitotic subtype was more abundant in Black patients (64.1% vs. 33.7%, P=0.002), indicated worse PFS in Black patients (HR=4.1, P=0.044) including the endometrioid histology (HR=6.1, P=0.024) and exhibited race-associated enrichment in cell cycle signaling and pathways in cancer including PLK1 and BIRC7. All of these aggressive molecular subtypes also indicated worse PFS in White patients, with unique enrichments in mitotic signaling different from Black patients. The aggressive molecular subtypes from TCGA were more common in Black endometrial cancer patients and indicated worse PFS in both Black and White patients. The mitotic subtypes also indicated worse PFS in Black patients with endometrioid histology. Enrichment patterns in mitotic signaling may represent therapeutic opportunities. Progression-free survival in White (A, C, E) or Black (B, D, F) endometrial cancer patients with versus without the copy number variant (CNV)-high subtype (A, B), the somatic copy number alterations (SCNA) cluster 4 subtype (C, D), or the transcript-based mitotic subtype (E, F). Survival distributions compared using log-rank testing. Bar chart displaying the proportion of patients with the more-aggressive copy number variant (CNV)-high subtype, the somatic copy number alterations (SCNA) cluster 4 subtype, or the transcript-based mitotic subtype (G). Fisher's exact testing was used to compare categorical variables. Venn diagram of the most significantly up-regulated transcripts in cell cycle signaling and in pathways in cancer in Black and/or in White endometrial cancer patients with mitotic versus non-mitotic subtypes with >2-fold change elevation and a false discovery rate<0.01 (H). [Display omitted] •Aggressive molecular subtypes were more frequently in Black endometrial cancers.•The mitotic subtype consistently indicated worse progression-free survival in Black patients.•Race-associated and –independent up-regulation in cell cycle signaling and cancer pathways.•Enrichment patterns in mitotic signaling may represent therapeutic opportunities.