Abstract
Megakaryocytic leukemia 1 (MKL1) acts as a transcription factor in the regulation of the immune system and is associated with cancer biology. However, its function in the infiltrating immune cells in breast cancer has not been explored. Our study aimed to analyze the expression of MKL1 in The Cancer Genome Atlas breast cancer dataset. The aim of this study was to evaluate the correlations between MKL1 expression, infiltrating immune cells, and immune control genes. Enriched signaling pathways and drug sensitivity analyses were also performed. Our results indicate that high MKL1 expression could predict better survival in breast cancer patients. MKL1 expression was associated with the expression and function of different immune cells, including T cells, B cells, natural killer cells, macrophages, neutrophils, and dendritic cells. The chromatin-modifying enzymes, cellular senescence, epigenetic regulation of gene expression, estrogen-dependent gene expression, and chromosome maintenance were differentially enriched in MKL1 low expression phenotype. Patients in the high MKL1 expression group showed sensitivity to paclitaxel, while those in the low expression group showed potential sensitivity for cisplatin and docetaxel. In conclusion, MKL1 might act as a potential biomarker of prognostic value for immune infiltration and drug sensitivity in breast cancer.
Highlights
Breast cancer, known as one of the most common malignancies among women worldwide, raises concerns nowadays [1]
Our results showed that Megakaryocytic leukemia 1 (MKL1) expression was associated with the tumor microenvironment (TME) in breast cancer and could predict breast cancer patient chemosensitivity and survival status
Analysis of the infiltration levels of immune cells To evaluate the association between tumor-infiltrating immune (TIL) cells and the expression of MKL1 in breast cancer, we first evaluated the expressed fraction of TIL cells using the single sample Gene Set Enrichment Analysis algorithm by comparing the breast cancer gene expression matrix with those of the signatures from 22 reported TIL cell types [26]
Summary
Known as one of the most common malignancies among women worldwide, raises concerns nowadays [1]. Aggressive proliferation and invasion, resistance to chemotherapy, and evasion of immune surveillance make breast cancer prone to relapse and metastasis [2]. With an improved understanding of tumor behavior, its microenvironment, and host factors, immunotherapy strategies have been promising for breast cancer treatment [3,4,5,6,7,8,9]. Blocking naive CD4+ T cells from entering into breast cancer tumors significantly decreases tumor-infiltrating Tregs and prevents tumor progression [11]. The CD47-immune signature was found to be related to the presence of tumor-infiltrating immune cells, like T cells, dendritic cells (DCs), and neutrophils, and could predict the survival of breast cancer patients [12]
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