Abstract 2154: Differential expression of the PI3K-Akt signaling pathway pre and post chemotherapy in relation to hormonal profile in African women

Abstract

Abstract Background: Breast cancer (BC) is the most common cancer in US and Canadian women. Despite therapeutic advances, it remains the second leading cause of female cancer mortality. Aggressive breast cancers are represented as a clinical (inflammatory BC or locally advanced BC) or as a biopathological form (triple negative BC or HER2+ BC). These aggressive forms have a poor prognosis. In the US, African Americans have a 41% higher BC death rate than Caucasians women. As observed in the US, in African Gabon women, a more aggressive and cases of triple negative BC are found. Aggressive BC are mainly associated with African women. At this stage, chemotherapy is the main therapeutic treatment but chemoresistance is the major hurdle. One solution to chemoresistance would be to found candidates biomarkers that predict therapeutic responses. The goal of our study was to establish an RNA signature that could differentiate chemosensitive from chemoresistant patients in BC African women. Methods: RNA sequencing technique was used to establish expression profiling in African women before and after chemotherapy using three groups of aggressive BC patients treated with: Doxorubicin, 5-Fluorouracil or Navelbine. We first isolated RNA from tissues fixed in paraffin and sequenced it via the Nextseq 2000 system. A tximport (v1.20.0) and DESeq2 (v1.26.0) analysis then identified significantly and differentially expressed transcripts between the different groups. Results: In the doxorubicin group, post-chemotherapy patients had 962 significant genes out of the 46461 transcripts compared to pre-chemotherapy patients. The post-chemotherapy 5-FluoroUracil group had 3723 significant genes out of 43821 transcripts compared to pre-chemotherapy Fluorouracil group and the post-chemotherapy Navelbine group had 980 significant genes out of 44689 transcripts compared to pre-chemotherapy Navelbine group. Relevant overexpressed genes were selected for validation by immunohistochemistry (IHC). We found an enrichment in the KEGG and PI-3K/Akt pathways and observed that Akt downstream substrates were express differently between pre- and post-chemotherapy patients. Conclusion: Our study suggests that some of the overexpressed post chemotherapy genes could serve as biomarkers of aggressive BC. This is the first study in Canada to investigate Doxorubicin, Flurouracile and Navelbine chemoresistance-related genes in African women and could lead to the discovery of diagnostic markers and therapeutic targets. Citation Format: Hurette Junie Chansi Kengni. Differential expression of the PI3K-Akt signaling pathway pre and post chemotherapy in relation to hormonal profile in African women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2154.