Breast cancer accounts for the highest incidence of tumors in women. Immune infiltrating of the tumor microenvironment positively correlates with the overall survival of breast cancer patients. PLAT can affect the development of many cancers, but its mechanism in breast cancer is unclear. We assessed the correlation between PLAT and immune infiltrating in breast cancer based on the TCGA database. Patients and Methods: The expression and DNA methylation of PLAT in breast cancer with different clinical characteristics was tested by Wilcoxon signed rank test and displayed by box plot. Sequentially, Kaplan-Meier plot was employed to compare the difference in overall survival rates between patients with different expressed levels. Univariate and multivariate Cox regression analyses were used to validate whether PLAT is an independent prognostic factor of breast cancer. After that, GO, KEGG, and gene-set enrichment analysis were employed to do functional enrichment analysis. Finally, TIMER, TISIDB database, and ssGSEA algorithm were used to assess the correlation between PLAT expression and various immune characteristics. The correlation between PLAT expression and DNA methylation was examined by Pearson correlation coefficient. Results: PLAT displays differential expression levels in breast cancer patients with various clinical characteristics. As an independent protective factor for breast cancer, PLAT may significantly correlate with the immune status of breast cancer by adjusting many immune molecules and affecting the immune infiltration in the tumor microenvironment. DNA methylation of PLAT downregulates the gene expression and affects the prognosis of breast cancer. Conclusion:PLAT can be considered a potential biomarker to predict breast cancer prognosis and might contribute to the development of immunological treatment strategies.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) and are associated with thyroid diseases. Our previous study reported that 2,3',4,4', could induce thyroid dysfunction and the rat thyroid tissues exhibit abnormal mitochondrial ultrastructure. However, the more specific effects of PCB118 on mitochondria and the relationship between mitochondria and thyroid dysfunction remain unclear. In this study, Wistar rats were injected with PCB118 intraperitoneally at 0, 10, 100, and 1000 μg/kg/d for 13 weeks and FRTL-5 rat thyroid cells were treated with PCB118 (0, 0.25, 2.5, and 25 nM) for 24 hr, which did not influence the general conditions of rats and FRTL-5 cells viability. The detection of serum levels of thyroid hormones (THs) and the expression of sodium/iodide symporter (NIS) protein demonstrated that thyroid function was impaired after PCB118 exposure. Transmission electron microscopy showed mitochondrial damage in the thyroids of PCB118treated rats. Biological processes analysis revealed that differentially expressed mRNAs in thyroid tissues induced by PCB118 were enriched in reactive oxygen species (ROS) metabolic process, hydrogen peroxide metabolic process, and hydrogen peroxide catabolic process. Moreover, mRNA expression of mitochondrial respiratory chain genes NDUFB3, UQCRC2, COX17, ATP5I and ATP5E decreased in PCB118treated groups. In vivo and in vitro data showed that ROS production increased significantly after PCB118 exposure, accompanied by increased levels of phospho-c-Jun N-terminal kinase (P-JNK). Taken together, these results suggest that PCB118 could damage mitochondria by increasing oxidative stress and PCB118-induced thyroid dysfunction may be related to ROS-dependent activation of the JNK pathway.

Melanoma is becoming increasingly common worldwide, with high rates of transformation into malignancy compared to other skin lesions. The prognosis of patients with melanoma at an advanced stage is highly unsatisfying despite the development of immunotherapy, target therapy, or combinative therapy. The major barrier to exploiting immune checkpoint therapies and achieving the best benefits clinically is resistance that can easily develop if regimens are not selected appropriately. In this study, we investigated the possibility of using immune-related genes to predict patient survival and their responses to immune checkpoint blocker therapies with the expression profiles available at The Cancer Genome Atlas (TCGA) Program plus expression data from the Gene Expression Omnibus (GEO) for validation. A five gene signature that is highly correlated with the local infiltration of cytotoxic lymphocytes in the tumor microenvironment was identified, and a scoring model was developed with stepwise regression after multivariate Cox analyses. The score calculated strongly correlates with Breslow depth, and this model effectively predicts the prognosis of patients with melanoma, whether primary or metastasized. It also depicts the heterogenous immune-related nature of melanoma by revealing different predicted responses to immune checkpoint blocker therapies through its correlation to tumor immune dysfunction and exclusion (TIDE) score.

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