TY - JOUR
T1 - Development and validation of Ran as a prognostic marker in stage I and stage II primary breast cancer
AU - El-Tanani, Mohamed
AU - Platt-Higgins, Angela
AU - Nsairat, Hamdi
AU - Matalka, Ismail I
AU - Ahmed, Khaled Abdul-Aziz
AU - Zhang, Shu-Dong
AU - Alshaer, Walhan
AU - Awidi, Abdalla
AU - Matchett, Kyle B
AU - Aljabali, Alaa A
AU - Mishra, Vijay
AU - Serrano-Aroca, Ángel
AU - Tambuwala, Murtaza M
AU - Rudland, Philip S
N1 - Copyright © 2023. Published by Elsevier Inc.
PY - 2023/9/15
Y1 - 2023/9/15
N2 - PURPOSE: Existing prognostic biomarkers are inadequate for stratifying breast cancer patients with the highest risk of tumor progression at the time of diagnosis. Here, we demonstrate that the small GTPase Ran has predictive value for breast cancer (BC) patients as a whole, and for specific BC subtypes.PATIENTS AND METHODS: Ran expression was quantified by immunohistochemistry in 263 patients with primary breast cancer diagnosed at the Breast Unit, Royal Liverpool Hospital. Additionally as an independent validation, we also analyzed the mRNA expressions of Ran, ER, PR, and Cerb-2, the triple-negative endocrine receptors, and their associations with patient survival in a combined patient cohorts of multiple public datasets (n = 1079). We analyzed the data with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided.RESULTS: Ran nuclear, cytoplasmic, and total staining are substantially associated with poor survival, independent of conventional prognostic markers such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and lymph node status. According to the datasets, Ran was significantly correlated with distant metastasis-free survival (DMFS) and relapse-free survival (RFS).CONCLUSION: We found that Ran expression is a unique predictive biomarker for patient survival, metastasis, and tumor relapse. This biomarker could be used for diagnostic purposes, using formalin-fixed, paraffin-embedded tumor biopsy samples from breast cancer patients in the early stages.
AB - PURPOSE: Existing prognostic biomarkers are inadequate for stratifying breast cancer patients with the highest risk of tumor progression at the time of diagnosis. Here, we demonstrate that the small GTPase Ran has predictive value for breast cancer (BC) patients as a whole, and for specific BC subtypes.PATIENTS AND METHODS: Ran expression was quantified by immunohistochemistry in 263 patients with primary breast cancer diagnosed at the Breast Unit, Royal Liverpool Hospital. Additionally as an independent validation, we also analyzed the mRNA expressions of Ran, ER, PR, and Cerb-2, the triple-negative endocrine receptors, and their associations with patient survival in a combined patient cohorts of multiple public datasets (n = 1079). We analyzed the data with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided.RESULTS: Ran nuclear, cytoplasmic, and total staining are substantially associated with poor survival, independent of conventional prognostic markers such as estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and lymph node status. According to the datasets, Ran was significantly correlated with distant metastasis-free survival (DMFS) and relapse-free survival (RFS).CONCLUSION: We found that Ran expression is a unique predictive biomarker for patient survival, metastasis, and tumor relapse. This biomarker could be used for diagnostic purposes, using formalin-fixed, paraffin-embedded tumor biopsy samples from breast cancer patients in the early stages.
KW - Breast cancer
KW - Diagnostic
KW - RAN
KW - HER2
KW - Immuno histology
KW - Estrogen receptor
UR - http://www.scopus.com/inward/record.url?scp=85166273321&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2023.121964
DO - 10.1016/j.lfs.2023.121964
M3 - Article
C2 - 37473800
SN - 0024-3205
VL - 329
SP - 121964
JO - Life Sciences
JF - Life Sciences
M1 - 121964
ER -
