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Abstract
BackgroundTo date, breast cancer remains the primary cause of tumor-related death among women, even though some leap-type developments of oncology have been done to slash the mortality. Considering the tumor heterogeneity and individual variation, the more reliable biomarkers are required to be identified for supporting the development of precision medicine in breast cancer.MethodsBased on the TCGA-BRCA and METABRIC databases, the differently expressed RNA binding proteins (RBPs) between tumor and normal tissues were investigated. In this study, we focused on the communal differently expressed RBPs in four subtypes of breast cancer. Lasso-penalized Cox analysis, Stepwise-multivariate Cox analysis and Kaplan–Meier survival curve were performed to identify the hub RBP-coding genes in predicting prognosis of breast cancer, and a prognostic model was established. The efficiency of this model was further validated in other independent GSE20685, GSE4922 and FUSCC-TNBC cohorts by calculating the risk score and performing survival analysis, ROC and nomogram. Moreover, pathologic functions of the candidate RBPs in breast cancer were explored using some routine experiments in vitro, and the potential compounds targeting these RBPs were predicted by reviewing the Comparative Toxicogenomics Database.ResultsHere, we identified 62 RBPs which were differently expressed between the tumor and normal tissues. Thereinto, three RBPs (MRPL12, MRPL13 and POP1) acted as independent risk factors, and their expression pattern also correlated with poor prognosis of patients. A prognostic model, built with these 3-RBPs, possessed statistical significance to predict the survival probability of patients with breast cancer. Furthermore, experimental validations showed that down-regulating the expression of endogenous MRPL12, MRPL13 or POP1 could dramatically suppress the cellular viability and migration of breast cancer cells in vitro. Besides, some compounds (such as the Acetaminophen, Urethane and Tunicamycin) were predicted for curing breast cancer via targeting MRPL12, MRPL13 and POP1 simultaneously.ConclusionThis study identified and established a 3-RBPs-based signature and nomogram for predicting the survival probability of patients with breast cancer. MRPL12, MRPL13 and POP1 might act as oncogenes in maintaining cellular viability and accelerating metastasis of breast cancer cells, implying the possibility of which to be designed as biomarkers and/or therapeutic targets for breast cancer.
Highlights
Breast cancer is an extraordinarily heterogeneous set of neoplasms with sophisticated pathogenesis and alarming incidence, especially being a formidable threat to women
There were 171 RNA-binding proteins (RBPs) differently expressed in tumor tissues of the Luminal A subtype, 179 RBPs differently expressed in the Luminal B subtype, 81 RBPs differently expressed in the human epidermal growth factor receptor 2 (HER2)-riched subtype while 252 RBPs differently expressed in TNBC samples (Figure 2A and Supplementary Table 4)
62 differently expressed RBPs were communal in four subtypes of breast cancer, wherein 24 RBPs were up-regulated but 38 RBPs were down-regulated in tumor tissues (Figure 2B and Supplementary Table 4)
Summary
Breast cancer is an extraordinarily heterogeneous set of neoplasms with sophisticated pathogenesis and alarming incidence, especially being a formidable threat to women. Advances in the early diagnosis and clinical intervention slashed the mortality of breast cancer significantly, breast cancer remains a feared, refractory and primary cause of tumor-related death among women. Following a curative intent while avoiding being overtreated, the novel personalized and precision medicine that constructed upon the set of reliable tumor biomarkers and targets are emerging and ongoing. RNA-binding proteins (RBPs) are ubiquitously expressed in cells and play important roles in regulating the cellular physiological and pathological processes [2]. Breast cancer remains the primary cause of tumor-related death among women, even though some leap-type developments of oncology have been done to slash the mortality. Considering the tumor heterogeneity and individual variation, the more reliable biomarkers are required to be identified for supporting the development of precision medicine in breast cancer
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