RT Journal Article SR Electronic T1 High Expression of p62 and ALDH1A3 Is Associated With Poor Prognosis in Luminal B Breast Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3299 OP 3312 DO 10.21873/anticanres.15818 VO 42 IS 7 A1 AYAKA OZAKI A1 HITOMI MOTOMURA A1 SHOMA TAMORI A1 CHOTARO ONAGA A1 YUKA NAGASHIMA A1 MAHO KOTORI A1 CHIKA MATSUDA A1 AKARI MATSUDA A1 NANAKO MOCHIZUKI A1 TSUGUMICHI SATO A1 YASUSHI HARA A1 KEIKO SATO A1 YOHEI MIYAGI A1 YOJI NAGASHIMA A1 TAKEHISA HANAWA A1 YOHSUKE HARADA A1 YUYUN XIONG A1 KAZUNORI SASAKI A1 SHIGEO OHNO A1 KAZUNORI AKIMOTO YR 2022 UL http://ar.iiarjournals.org/content/42/7/3299.abstract AB Background/Aim: p62 (also known as sequestosome 1) is involved in cancer progression, and high expression of p62 indicates poor clinical outcome in several cancer types. However, the association between p62 gene expression and cancer stem cells (CSCs) in breast cancer subtypes remains unclear. Materials and Methods: In the present study, genomic datasets of primary breast cancer (The Cancer Genome Atlas, n=593; and Molecular Taxonomy of Breast Cancer International Consortium, n=2,509) were downloaded. p62 Expression was then examined in normal and breast cancer tissues derived from the same patients. Kaplan-Meier and multivariate Cox regression analyses were employed to evaluate disease-specific survival. Next, the effect on cell viability and in vitro tumor-sphere formation of p62 knockdown using targeted small interfering RNA was assessed by using cells with high activity of aldehyde dehydrogenase 1 (ALDH1high). Results: Patients with normal-like, luminal A or luminal B breast cancer with p62high had poor prognosis. Furthermore, patients with p62high ALDH1A3high luminal B type also exhibited poor prognoses. Knockdown of p62 suppressed viability and tumor-sphere formation by ALDH1high cells of the luminal B-type cell lines BT-474 and MDA-MB-361. These results suggest that p62 is essential for cancerous progression of ALDH1-positive luminal B breast CSCs, and contributes to poor prognosis of luminal B breast cancer. Conclusion: p62 is potentially a prognostic marker and therapeutic target for ALDH1-positive luminal B breast CSCs.