AUTHOR=Liu Xiuming , Teng Yuee , Wu Xin , Li Zhi , Bao Bowen , Liu Yunpeng , Qu Xiujuan , Zhang Lingyun TITLE=The E3 Ubiquitin Ligase Cbl-b Predicts Favorable Prognosis in Breast Cancer JOURNAL=Frontiers in Oncology VOLUME=10 YEAR=2020 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00695 DOI=10.3389/fonc.2020.00695 ISSN=2234-943X ABSTRACT=

Background: Casitas B-lineage lymphoma proto-oncogene-b (Cbl-b) is an E3 ubiquitin-protein ligase and a signal-transducing adaptor protein involved in the development and progression of cancer. Despite the known functions of Cbl-b, its role in breast cancer remains unclear. The aim of this study is to explore the prognostic value of Cbl-b in breast cancer.

Methods: Cbl-b expression was analyzed by immunohistochemistry in 292 breast cancer patients from the First Hospital of China Medical University between 1999 and 2008. Kaplan-Meier curve and Cox proportional hazards regression were used to analyze the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Nomogram was constructed based on these prognostic factors.

Results: Cbl-b expression was detected in 54.1% (158/292) breast cancer tissue samples. Cbl-b expression was correlated with DFS (p = 0.033), but was not significantly associated with the known clinic-pathological factors in this study. Log-rank analysis indicated that Cbl-b expression was correlated with better OS (p = 0.013) and DFS (p = 0.016). Multivariate analysis showed that Cbl-b expression was an independent prognostic factor in breast cancer. The nomogram we built for predicting OS was integrated with Cbl-b expression, age, tumor size, lymph node metastasis and histological grade. Except tumor size, all the above factors and date of diagnosis were used to construct the DFS nomogram. The C-indexes of the nomograms were 0.735 and 0.678, respectively. Our new clinical model was superior to the TNM staging for prediction of OS.

Conclusion: Cbl-b expression independently predicts favorable prognosis in breast cancer. Cbl-b expression, combined with other variables could be more precise clinical predictive models for predicting OS and DFS in patients with breast cancer.