Seven genes were closely associated with ALDH1 in triple negative breast cancer

Background : Aldehyde dehydrogenase1 (ALDH1) is widely accepted as a marker of normal and malignant breast stem cells. We reported that ALDH1 expression was associated with aggressive phenotypes and poor clinical outcome of breast cancer patients. However, mechanics of how ALDH1 affects cancer stem cell features is not known. Aim : To examine genes associated with ALDH1 and find novel druggable targets for the future cancer stem cell therapy. Methods : ALDH1-positive and ALDH1-negative cells were dissected by a laser capture microdissection from 5 ALDH1 positive triple negative breast cancer samples. A differential analysis of mRNA expression was performed between ALDH1 positive and negative breast cancer cells in each sample by Affymetrix GeneChip microarrays. 1) Microarray analysis suite (MAS5) and robust multi-chip average (RMA) were used as preprocessing algorithms to analyze gene expression data and to extract genes differently expressed between ALDH1 positive and negative cells. 2) The network analysis was performed with extracted genes with MAS5 by the comprehensive information platform “KeyMolnet TM ”. Results : 1) 54,682 genes were extracted and 32,264 genes were selected after eliminating background noise. One hundred and four genes: 63 up-regulated and 41 down-regulated, were extracted in ALDH1-positive cells by MAS5, while only 2 up-regulated genes by RMA. H19 was a gene that was commonly extracted by both algorithms. 2) The network with 104 genes was constructed and BRD4, SMAD4, Pitx3, RARa, MUC1, HASH1 and C/EBPb were identified as genes with the closest distance to ALDH1. Conclusions : Most of extracted 7 genes have been already known to exert critical roles for maintaining stem cell features, providing a rationale of ALDH1 for the stem cell marker of breast cancer. These genes including H19 could be targets of the cancer stem cell therapy for treating incurable breast cancer. Citation Format: Takashi Ishikawa, Kazutaka Narui, Akimitsu Yamada, Kumiko Kida, Hidetaka Shima, Chiho Endo, Shoko Adachi, Sadatoshi Sugae, Yohei Miyagi, Yasushi Ichikawa, Itaru Endo. Seven genes were closely associated with ALDH1 in triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1158.