Systematic Characterization of Expression Patterns and Immunocorrelations of Formin-Like Genes in Breast Cancer

乳腺癌中 Formin 样基因表达模式和免疫相关性的系统表征

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作者:Erli Gao, Xuehai Wang, Fengxu Wang, Siyuan Deng, Weiyi Xia, Rui Wang, Xiangdong Wang, Xinyuan Zhao, Haixin Qian

Background

Members of the formin-like gene (FMNL) family are required for cytoskeleton-related processes, and their expressions are implicated to the progression of a multitude of malignancies. However, there are insufficient studies on transcription factors and promising prognosis benefit of FMNLs during the genesis of breast cancer (BrCa).

Conclusions

The fact and result which we analyzed demonstrate FMNL1 as a diagnostic marker for TIICs by comprehensively elucidating the expression patterns and changeable prognostic implications of FMNLs in BrCa clinical applications.

Methods

The transcriptional levels of FMNL family members in primary BrCa tissues and their association with intrinsic subclasses were analyzed using the UALCAN database. Then, the prognostic values of FMNLs in BrCa patients were investigated via the Kaplan-Meier plotter. Moreover, the correlations between FMNL expression levels and immune infiltrations were analyzed using the TIMER database. In addition, the expression patterns of FMNLs in BrCa were investigated by single-cell RNA-sequencing (scRNA-seq) analysis and were validated by immunohistochemistry (IHC) staining.

Results

The transcriptional level of FMNL1 was shown to be considerably increased in BrCa. It is surprising that the transcriptional quantities of FMNL2 and FMNL3 were substantially reduced. In addition, during the comparison of several BrCa subclasses, FMNL1 and FMNL2 mRNA levels of patients with HER2-positive and triple-negative BrCa subclasses increased, while FMNL3 mRNA levels reduced. With the processions of experimentation, high FMNL1 expression was hopefully linked to well clinical outcome, while high FMNL2 expression predicted poor prognosis. Moreover, FMNL1 was highly expressed in tumor-infiltrating immune cells (TIICs) in tumor tissues. Last but not least, FMNL1 was highly expressed in TIICs and served as a gene marker for TIICs. Conclusions: The fact and result which we analyzed demonstrate FMNL1 as a diagnostic marker for TIICs by comprehensively elucidating the expression patterns and changeable prognostic implications of FMNLs in BrCa clinical applications.

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