Abstract
Currently, Stathmin1 (STMN1) and phospho-STMN1 levels in breast cancers and their clinical implications are unknown. We examined the expression of STMN1 and its serine phospho-site (Ser16, Ser25, Ser38, and Ser63) status by immunohistochemistry. Using Cox regression analysis, a STMN1 expression signature and phosphorylation profile plus clinicopathological characteristics (STMN1-E/P/C) was developed in the training set (n = 204) and applied to the validation set (n = 106). This tool enabled us to separate breast cancer patients into high- and low-risk groups with significantly different disease-free survival (DFS) rates (P < 0.001). Importantly, this STMN1-E/P/C model had a greater prognostic value than the traditional TNM classifier, especially in luminal subtype breast cancer (P = 0.002). Further analysis showed that patients in the low-risk group would benefit more from adjuvant paclitaxel-based chemotherapy (P = 0.002). In conclusion, the STMN1-E/P/C signature is a reliable prognostic indicator for luminal subtype breast cancer and may predict the therapeutic response to paclitaxel-based treatments, potentially facilitating individualized management.
Highlights
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related morbidity and mortality among women worldwide [1]
By analyzing two independent patient cohorts, we showed and validated for the first time that integrated STMN1 expression, phosphorylation status and known clinicopathological characteristics of cancer patients can predict clinical outcomes successfully, and exhibit a remarkable predictive value to guide appropriate treatment
In this study of breast cancer, STMN1 expression and the phosphorylation status of its multiple serine residues were better correlated with disease-free survival (DFS) than standard clinicopathological features
Summary
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related morbidity and mortality among women worldwide [1]. Comprehensive gene expression profiling has distinguished four major molecular subtypes of breast cancer with different clinical outcomes: luminal A, luminal B, HER2/neu and triple-negative [2,3,4]. The luminal A and B subtypes are collectively referred to as the luminal type, which accounts for 65–70% of breast cancers. Compared with other breast cancers, patients with luminal subtypes benefit from endocrine therapies and have a better prognosis. Long-term recurrence remains a major clinical problem. Additional markers to individualize treatment and prognosis are urgently needed
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