An Eleven-microRNA Signature Related to Tumor-Associated Macrophages Predicts Prognosis of Breast Cancer

Abstract

The dysregulation of microRNAs (miRNAs) has been known to play important roles in tumor development and progression. However, the understanding of the involvement of miRNAs in regulating tumor-associated macrophages (TAMs) and how these TAM-related miRNAs (TRMs) modulate cancer progression is still in its infancy. This study aims to explore the prognostic value of TRMs in breast cancer via the construction of a novel TRM signature. Potential TRMs were identified from the literature, and their prognostic value was evaluated using 1063 cases in The Cancer Genome Atlas Breast Cancer database. The TRM signature was further validated in the external Gene Expression Omnibus GSE22220 dataset. Gene sets enrichment analyses were performed to gain insight into the biological functions of this TRM signature. An eleven-TRM signature consisting of mir-21, mir-24-2, mir-125a, mir-221, mir-22, mir-501, mir-365b, mir-660, mir-146a, let-7b and mir-31 was constructed. This signature significantly differentiated the high-risk group from the low-risk in terms of overall survival (OS)/ distant-relapse free survival (DRFS) (p value < 0.001). The prognostic value of the signature was further enhanced by incorporating other independent prognostic factors in a nomogram-based prediction model, yielding the highest AUC of 0.79 (95% CI: 0.72–0.86) at 5-year OS. Enrichment analyses confirmed that the differentially expressed genes were mainly involved in immune-related pathways such as adaptive immune response, humoral immune response and Th1 and Th2 cell differentiation. This eleven-TRM signature has great potential as a prognostic factor for breast cancer patients besides unravelling the dysregulated immune pathways in high-risk breast cancer.

Knockdown of let‐7b in leukemia associated macrophages inhibit acute myeloid leukemia progression

“…According to biological information database, TLR was related to macrophage polarization, then microRNAs including let‐7b , let‐7e , let‐7i , miR146 , miR105 , miR223 and miR147 which regulated TLR and its downstream NF‐κB signaling pathway were selected for PCR verification and let‐7b , miR146 and miR147 were confirmed to be significantly up‐regulated in LAMs from AML‐refractory mice (Figure 3C). It was reported that let‐7b participated in the TAMs mediated growth of prostate cancer and breast cancer, 9,10 however its role was not reported in hematologic malignancies. Therefore, let‐7b was selected as the research target to modify LAM reprogram.…”

Identification of MicroRNAs Associated with Histological Grade in Early-Stage Invasive Breast Cancer

“…miRNAs comprise small noncoding RNA molecules that regulate gene expression post-transcriptionally and are involved in the onset, progression, and metastasis of breast cancer [ 19 , 20 ]. Recent studies reported that a diagnostic miRNA signature can be employed to assess tumor aggressiveness, drug response, and outcomes in patients with breast cancer [ 19 , 21 , 22 ]. Furthermore, miRNA expression profiles have been reported to be different for each molecular subtype of breast cancer [ 6 ].…”

Construction of stemness gene score by bulk and single-cell transcriptome to characterize the prognosis of breast cancer

“…Currently, several breast cancer prognosis-prediction models are available. Generally, these tools have been developed based on the selection of prognostic genes based on bulk RNA-seq data and internal validation [21][22][23]. Typically, internal validation is not sufficient to fully validate a model.…”