ABSTRACT
Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.
Subject(s)
Breast Neoplasms, Male , Humans , Female , Male , Single-Cell Gene Expression Analysis , Immunosuppression Therapy , Lipid Metabolism/genetics , Fatty AcidsABSTRACT
Drug resistance is a significant obstacle when treating triple-negative breast cancer (TNBC). Several studies have demonstrated that microRNAs (miRNAs) have essential roles in regulating drug resistance in different types of cancer. miR-33a-5p has previously been reported to be a tumor suppressor in several types of cancer. However, its role in breast cancer remains unknown. The present study aimed to investigate the role of miR-33a-5p in the chemoresistance of TNBC and uncover its potential molecular mechanisms. Cell Counting Kit-8 assay was used to examine cell proliferation, reverse transcription-quantitative PCR analysis was used to examine miR-33a levels, and western blotting and immunofluorescence assays were used to examine the expression of epithelial-mesenchymal transition (EMT)-associated proteins and of eukaryotic translation initiation factor 5A2 (eIF5A2). The results indicated that miR-33a-5p expression was lower in TNBC cells compared with non-TNBC cells. miR-33a-5p overexpression significantly improved the doxorubicin (Dox) sensitivity of TNBC cells, but not that of non-TNBC cells. It was then observed that Dox treatment inhibited miR-33a-5p expression and induced EMT in TNBC cells, by increasing the expression levels of vimentin, while decreasing the expression levels of E-cadherin. Furthermore, it was revealed that forced expression of miR-33a-5p attenuated Dox-induced EMT. eIF5A2 was identified as a potential target of miR-33a-5p, and miR-33a-5p overexpression inhibited the expression of eIF5A2. eIF5A2 inhibition, via its inhibitor GC7, sensitized TNBC cells to Dox and reversed Dox-induced EMT. Overall, the present study demonstrated that miR-33a-5p enhanced the sensitivity of TNBC cells to Dox, by suppressing eIF5A2 expression and reversing Dox-induced EMT, providing a potential therapeutic target for treating drug-resistant TNBC.
ABSTRACT
The incidence of synchronous multiple primary malignancies has been reported to be low. We report a rare case of synchronous lung squamous cell cancer and small cell lung cancer in an 82-year-old male patient. There is a lack of standard diagnostic criteria for multiple primary lung cancer. Two tumors with similar morphology are difficult to draw conclusions about the same lineage or different lineages. If the patient's physical condition permits, multiple tumors should be sampled and tested. Besides, imaging features are helpful for identification. It is advisable to diagnose synchronous multiple primary malignancies in an early stage, which contributes to a favorable outcome.
