Molecular characterization of early breast cancer onset to understand disease phenotypes in African patients

Pamela Derliche Tonouo, Esther Dina Bell,Arnol Auvaker Tiofack Zebaze, Eliane Ndounga, Sidonie Noa Ananga, Etienne Atenguena,Gustave Simo,Abdel Jelil Njouendou,Smiths S. Lueong

MEDICAL ONCOLOGY(2022)

引用 1|浏览8
暂无评分
摘要
Female breast cancer (BC) is the leading cause of cancer-related deaths worldwide with higher mortality rates and early onset in developing countries. The molecular basis of early disease onset is still elusive. We recruited 472 female breast cancer from two sub-Saharan African countries (Cameroon and Congo) between 2007 and 2018 and collected clinical data from these patients. To investigate the molecular drivers of early disease onset, we analyzed publicly available breast cancer molecular data from the cancer genome atlas (TCGA) and the gene expression omnibus (GEO) for copy number alteration, mutation and gene expression. Early BC onset (EOBRCA) (diagnosis before 45 years) was higher in African women compared with the TCGA cohort (51.7% vs 15.6%). The tumor grade, mitotic index, HER2 + phenotype, basal-like phenotype and ki67 were higher in EOBRCA for all cohorts. BC risk factors such as parity, breastfeeding early onset of menarche and use of hormonal contraceptives were significantly associated with EOBRCA ( p < 0.05). EOBRCA was equally associated with copy number alterations in several oncogenes including CDH6 and FOXM1 and tumor suppressor including TGM3 and DMBT1 as well as higher TP53 mutation rates (OR: 2.93, p < 0.01). There was a significant enrichment of TGFß signaling in EOBRCA with TGM3 deletions, which was associated with high expression of all SMAD transcription factors as well as WNT ligands. The Frizzled receptors FZD1 , FZD4 and FZD6 were significantly upregulated in EOBRCA, suggesting activation of non-canonical WNT signaling. Our data, suggest the implication of TGM3 deletion in early breast cancer onset. Further molecular investigations are warranted in African patients.
更多
查看译文
关键词
CAN,TGFß signaling,Early onset of breast cancer,Oncogene,Tumor suppressor
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要