Prognostic value of the ubiquitin ligase carboxyl terminus of the Hsc70‐interacting protein in postmenopausal breast cancer

Abstract

The carboxyl terminus of the Hsc70‐interacting protein (CHIP) is considered to induce the ubiquitination and degradation of several oncogenic proteins, and play a role in the inhibition of tumor progression and invasion under experimental conditions. However, the impact of CHIP expression on the prognosis of breast cancer patients has not yet been established. In this study, using an immunohistochemical method, 272 patients with invasive breast cancer were assessed for the expression of CHIP (graded scores 0‐3) and the statuses of biomarkers, such as estrogen receptor (ER), progesterone receptor (PgR), and HER2. The relationships between the statuses of CHIP and biomarkers as well as clinical features were also evaluated, and that between the expression of CHIP and patient prognosis was analyzed. We revealed that the strong expression of CHIP correlated with positive ER (P < 0.001), positive PgR (P < 0.001), and negative HER2 (P = 0.02). In postmenopausal patients, relapse‐free survival (RFS) was significantly better in the high CHIP group than in the low CHIP group (P = 0.042). In addition, RFS and cancer‐specific survival (CSS) were significantly better in patients with ER‐positive/CHIP score 3 tumors than in those with ER‐negative/CHIP score 0 tumors (RFS: P = 0.038, CSS: P = 0.0098). The methylation status of CHIP gene promoter did not always account for the down‐regulation of its expression. In conclusion, the overexpression of CHIP is a potent prognostic factor of a good prognosis in ER‐positive breast cancer patients in the postmenopausal phase.

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

“…66,67 We previously demonstrated that strong CHIP expression is correlated with ER positivity, PgR positivity and HER2 negativity, and identified CHIP expression as a potent prognostic factor in postmenopausal patients with invasive breast cancer. 68 Ozgur et al 69 reported that two miRNAs, miR-29a and miR-193b, are associated with breast cancer through their contact with HSP70.…”

One DNA Methylation Regulates CHIP Gene Expression of Human Breast Cancer and Predicts Recurrence

“…Even in ER-positive cases, the CpG9-methylated group showed no significant difference in recurrence rate compared to each of the ER-negative methylation groups. Previously, we reported the relationship between ER and CHIP protein expression (31), and recurrence-free survival was significantly better in the ER-positive cases with high CHIP expression than in ER-negative cases. However, although positive for ER, such cases with low CHIP expression tended to have worse recurrence-free survival than those with high CHIP expression.…”

Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer

“…Furthermore, El Ansari et al (2018) elucidated that high LAT1 expression levels are associated with high proliferation potential, as indicated by the high Nottingham Prognostic Index and Ki67 labeling index; high LAT1 expression levels are also a poor prognosis factor in luminal B-like type breast tumors. It has been postulated that luminal A-like and luminal B-like type tumors display signi cantly different proliferation abilities in ER-positive BCa (Kurozumi S et al 2016;Burstein H J et al 2019). Thus, a combinatorial chemotherapeutic approach is recommended because luminal B-like type tumors have an extremely high proliferation potential.…”