As an essential nutrient, copper’s redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity to treat copper-sensitive diseases may offer new strategies for specific disease treatments. In particular, copper concentration is typically higher in cancer cells, making copper a critical limiting nutrient for cancer cell growth and proliferation. Hence, intervening in copper metabolism specific to cancer cells may become a potential tumor treatment strategy, directly impacting tumor growth and metastasis. In this review, we discuss the metabolism of copper in the body and summarize research progress on the role of copper in promoting tumor cell growth or inducing programmed cell death in tumor cells. Additionally, we elucidate the role of copper-related drugs in cancer treatment, intending to provide new perspectives for cancer treatment.

Objective: Recent studies demonstrated that circulating tumor cells (CTCs) contribute to the metastasis of prostate cancer. Survivin knockout could inhibit epithelial-mesenchymal transition (EMT) and suppress several metastatic tumors. In this study, we examined the potential involvement of survivin in EMT in CTCs. Methods: CTCs were isolated from the peripheral blood of 100 patients with prostate cancer as EpCAM þ /CD45 À cells via FACS sorting and identified by immunofluorescence staining of prostate-specific antigen (PSA). CTCs and DU145 cells were transfected with survivin siRNA. Then, the levels of survivin, E-cadherin, and vimentin in CTCs and DU145 cells were detected via immunofluorescence staining, and the invasiveness of CTCs and DU145 cells was examined using a Transwell chamber. Results: The results revealed the abundant expression of PSA in the cytoplasm of CTCs. Transfection of survivin siRNA significantly decreased the levels of survivin and vimentin in CTCs and DU145, whereas that of E-cadherin was significantly increased, suggesting survivin plays an important role in EMT of CTCs. In addition, survivin siRNA significantly inhibited the invasiveness of CTCs and DU145 cells. Conclusions: Survivin plays an important role in EMT of CTCs in prostate cancer, which might mediate the metastasis and invasion of prostate cancer.

Background. Hepatocellular carcinoma (HCC) remains a challenging medical problem. Cuproptosis is a novel form of cell death that plays a crucial role in tumorigenesis, angiogenesis, and metastasis. However, it remains unclear whether cuproptosis-related genes (CRGs) influence the outcomes and immune microenvironment of HCC patients. Method. From The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we obtained the mRNA expression file and related clinical information of HCC patients. We selected 19 CRGs as candidate genes for this study according to previous literature. We performed a differential expression analysis of the 19 CRGs between malignant and precancerous tissue. Based on the 19 CRGs, we enrolled cluster analysis to identify cuproptosis-related subtypes of HCC patients. A prognostic risk signature was created utilizing univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. We employed independent and stratification survival analyses to investigate the predictive value of this model. The functional enrichment features, mutation signatures, immune profile, and response to immunotherapy of HCC patients were also investigated according to the two molecular subtypes and the prognostic signature. Results. We found that 17 CRGs significantly differed in HCC versus normal samples. Cluster analysis showed two distinct molecular subtypes of cuproptosis. Cluster 1 is preferentially related to poor prognosis, high activity of immune response signaling, high mutant frequency of TP53, and distinct immune cell infiltration versus cluster 2. Through univariate and LASSO Cox regression analyses, we created a cuproptosis-related prognostic risk signature containing LIPT1, DLAT, MTF1, GLS, and CDKN2A. High-risk HCC patients were shown to have a worse prognosis. The risk signature was proved to be an independent predictor of prognosis in both the TCGA and ICGC datasets, according to multivariate analysis. The signature also performed well in different stratification of clinical features. The immune cells, which included regulatory T cells (Treg), B cells, macrophages, mast cells, NK cells, and aDCs, as well as immune functions containing cytolytic activity, MHC class I, and type II IFN response, were remarkably distinct between the high-risk and low-risk groups. The tumor immune dysfunction and exclusion (TIDE) score suggested that high-risk patients had a higher response rate to immune checkpoint inhibitors than low-risk patients. Conclusion. This research discovered the potential prognostic and immunological significance of cuproptosis in HCC, improved the understanding of cuproptosis, and may deliver new directions for developing more efficacious therapeutic techniques for HCC patients.

Hepatocellular carcinoma (HCC) remains a worldwide health problem. Mounting evidence indicates that exhausted T cells play a critical role in the progress and treatment of HCC. Therefore, a detailed characterisation of exhausted T cells and their clinical significance warrants further investigation in HCC. Based on the GSE146115, we presented a comprehensive single‐cell Atlas in HCC. Pseudo‐time analysis revealed that tumour heterogeneity progressively increased, and the exhausted T cells gradually appeared during tumour progression. Functional enrichment analysis revealed that the evolutionary process of exhausted T cells mainly contained the pathway of cadherin binding, proteasome, cell cycle, and T cell receptor regulation of apoptosis. In the International Cancer Genome Consortium database, we divided patients into three clusters with the T cell evolution‐associated genes. We found that the exhausted T cells are significantly related to poor outcomes through immunity and survival analysis. In The Cancer Genome Atlas database, the authors enrolled weighted gene co‐expression network analysis, univariate Cox analysis, and Lasso Cox analysis, then screened the 19 core genes in T cells evolution and built a robust prognostic model. This study offers a fresh view on evaluating the patients' outcomes from an exhausted T cells perspective and might help clinicians develop therapeutic systems.

Cirrhosis is a serious liver disease with an unclear etiology and pathogenesis. Previous studies suggest a correlation between circulating copper and cirrhosis. However, whether circulating copper is a risk factor for cirrhosis is currently controversial because the liver is a major organ of copper metabolism and cirrhosis affects copper circulation. To address this, we used a mendelian randomization to explore the effect of circulating copper concentration on the risk of cirrhosis. We selected instrumental variables (IVs) of circulating copper from genome-wide association studies and analyzed two datasets from FinnGen, one for cirrhosis in general and the other for cirrhosis caused by non-alcoholic fatty liver disease (NAFLD). The inverse-variance weighted method was primarily used for mendelian randomization analysis. We created two SNP IVs that were associated with circulating copper, and their genetic associations with cirrhosis were extracted from the two datasets. The cirrhosis-related dataset included 811 cirrhosis patients and 273,592 controls, while the dataset for cirrhosis caused by NAFLD included 437 cirrhosis patients and 216,861 controls. Mendelian randomization analysis predicted a significant association between higher levels of circulating copper and increased risk of cirrhosis of liver (OR = 1.82, 95% CI: 1.30 to 2.54, P < 0.001). Additionally, higher levels of circulating copper were also associated with increased risk of cirrhosis of liver caused by NAFLD (OR = 1.68, 95% CI: 1.08 to 2.60, P = 0.021). The study suggests that higher levels of circulating copper may be a pathogenic risk factor for cirrhosis, providing important insights for the prevention and treatment of cirrhosis.