The Significance of p-AKT1 as a Prognostic Marker and Therapeutic Target in Patients With Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor-2-Positive Early Breast Cancer

김지예; 박찬섭; 장세경; 설혜실; 성민기; 노우철; 박인철; 김현아

doi:10.4048/jbc.2022.25.e43

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자료유형: 학술저널

저자정보: 김지예 (Division of Fusion Radiology Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.) 박찬섭 (Department of Surgery Korea Cancer Center Hospital Korea Institute of Radiological and Medical Scie) 장세경 (Division of Fusion Radiology Research Korea Institute of Radiological and Medical Sciences Seoul Ko) 설혜실 (Department of Pathology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.) 성민기 (Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.) 노우철 (Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.) 박인철 (Division of Fusion Radiology Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.) 김현아 (Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea.)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.25 No.5

발행연도: 2022.10

수록면: 387 - 403 (17page)

DOI: 10.4048/jbc.2022.25.e43

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Purpose: Phosphorylated AKT1 (p-AKT1) at Ser473 is a functional isoform of AKT and a key component of the PI3K/mTOR/AKT pathway. This study aimed to evaluate the prognostic significance of p-AKT1 (Ser473) based on the molecular subtypes of breast cancer. Methods: To investigate the prognostic value of p-AKT1 (Ser473), we performed a retrospective chart review of patients with breast cancer. Data on p-AKT1 (Ser473) positivity, hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) expression status, and other clinicopathological factors were obtained. Furthermore, the therapeutic effect of blocking p-AKT1 (Ser473) in breast cancer cells was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis assay, apoptosis protein array, and western blot analysis. Results: A total of 3,044 patients were evaluated, and the median follow-up time was 43 (range: 0–125) months. In patients with HR-positive and HER2-positive disease, the p-AKT1 (Ser473)-positive group had worse disease-free survival (DFS) than the p-AKT1 (Ser473)-negative group (hazard ratio, 1.9; 95% confidence interval, 1.1–3.5; p = 0.024). In the multivariate analysis, p-AKT1 (Ser473) remained a significantly worse prognostic factor in patients with HR-positive/HER2-positive breast cancer (p = 0.03). There was no difference in DFS according to p-AKT1 (Ser473) status among patients with other breast cancer subgroups. In vitro analysis showed that blocking p-AKT1 (Ser473) levels enhanced trastuzumab-induced cell death in HR-positive/HER2-positive and p-AKT1 (Ser473)-positive breast cancer cells. Conclusion: p-AKT1 (Ser473) is a prognostic marker for poor outcomes in patients with HR-positive/HER2-positive breast cancer and may have a potential value as a therapeutic target.

#AKT1 Protein #Breast Neoplasms #Disease-Free Survival #Prognosis

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