多平台生物信息学图谱分析鉴定TTK和NEK2为三阴性乳腺癌中与生存相关的驱动因子

Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of ER, PR, and HER2 receptors, limiting targeted therapeutic options and contributing to poorer outcomes among women. Prior evidence from our group indicates that mitotic kinases TTK and NEK2 are frequently overexpressed in TNBC, promoting centrosome amplification and invasive behaviour. Therefore, we aim to further explore how these mitotic kinases impact biological processes and the overall survival of TNBC patients. Hypothesis: Mitotic kinases, such as TTK and NEK2, play a pivotal role in EMT and metastatic processes in TNBC, while their overexpression leads to a lower overall survival of TNBC patients. Method: To functionally assess this hypothesis, we performed a series of bioinformatic analyses using the TCGA and STRING databases to evaluate the molecular processes associated with TTK and NEK2 expression. We also collected information from the Kaplan Meier (KM) Plotter database to evaluate the correlation between TTK and NEK2 expression on BC patients' overall survival. Results: mRNA expression profiles from TCGA demonstrated significantly elevated TTK and NEK2 levels across TNBC groups. Moreover, high expression of both mitotic kinases correlated with reduced overall survival in KM analyses. STRING network analysis revealed enrichment for beta-catenin binding, cell-to-cell junction regulation, and mesenchymal differentiation, supporting a role for these kinases in EMT-associated processes. Conclusion: Collectively, these data provide complementary bioinformatic evidence that the mitotic kinases TTK and NEK2 contribute to EMT activation and invasive potential in TNBC. Their overexpression in patient tumors correlates with poor survival outcomes. Thus, these results highlight TTK and NEK2 as promising molecular targets for limiting TNBC progression and metastasis.