Identification of the novel exhausted T cell CD8 + markers in breast cancer.

Cancer is one of the most concerning public health issues and breast cancer is one of the most common cancers in the world. The immune cells within the tumor microenvironment regulate cancer development. In this study, single immune cell data sets were used to identify marker gene sets for exhausted CD8 + T cells (CD8Tex) in breast cancer. Machine learning methods were used to cluster subtypes and establish the prognostic models with breast cancer bulk data using the gene sets to evaluate the impacts of CD8Tex. We analyzed breast cancer overexpressing and survival-associated marker genes and identified CD8Tex hub genes in the protein-protein-interaction network. The relevance of the hub genes for CD8 + T-cells in breast cancer was evaluated. The clinical associations of the hub genes were analyzed using bulk sequencing data and spatial sequencing data. The pan-cancer expression, survival, and immune association of the hub genes were analyzed. We identified biomarker gene sets for CD8Tex in breast cancer. CD8Tex-based subtyping systems and prognostic models performed well in the separation of patients with different immune relevance and survival. CRTAM, CLEC2D, and KLRB1 were identified as CD8Tex hub genes and were demonstrated to have potential clinical relevance and immune therapy impact. This study provides a unique view of the critical CD8Tex hub genes for cancer immune therapy.

Flexocatalysis Enhances Tumor Photodynamic Therapy.

Photodynamic therapy (PDT) is long-standing suffered from elevated tumor interstitial fluid pressure (TIFP) and prevalent hypoxic microenvironment within the solid malignancies. Herein, sound-activated flexocatalysis is developed to overcome the dilemma of PDT through both enhancing tumor penetration of photosensitizers by reducing TIFP and establishing an oxygen-rich microenvironment. In detail, a Schottky junction is constructed by flexocatalyst MoSe2 nanoflowers and Pt. Subsequently, the Schottky junction is loaded with the photosensitizer indocyanine green (ICG) and encapsulated within tumor cytomembrane to constitute a bionic-flexocatalytic nanomedicine (MPI@M). After targeting the tumor, MPI@M orchestrates flexocatalytic water splitting in tumor interstitial fluid under acoustic stimulation to lower TIFP, which boosted the tumor penetration of ICG. Concurrently, the oxygen released from the flexocatalytic water splitting overcomes the limitation of hypoxia against PDT. Furthermore, superfluous singlet oxygen generated by PDT can induce mitochondrial dysfunction for further tumor cell apoptosis. After 60 min of flexocatalysis, both the 30% decrease of TIFP and the relieved tumor hypoxia are observed, significantly promoting the therapeutic effect of PDT. Consequently, MoSe2/Pt junction nanoflowers, with the excellent flexocatalytic performance, hold significant potential for future applications in biocatalytic cancer therapies.

Near-infrared-II photocharging nanozyme for enhanced tumor immunotherapy.

In tumor therapy, copper (Cu)-based nanozymes with peroxidase-like activity play a crucial role in converting hydrogen peroxide into hydroxyl radicals (OH). This process induces immunogenic cell death, which in turn activates the body's immune response, enhancing the efficacy of tumor immunotherapy. Nonetheless, the efficiency of this reaction is curtailed due to the oxidation of Cu(I) to Cu(II), leading to the self-depletion of the nanozyme's activity and an insufficient yield of OH for effective immunotherapeutic activation. To surmount this challenge, our research introduces a photocharging self-doped semiconductor nanozyme, copper sulfide (Cu9S8). The photocharging effect enables the nanozyme to convert internal Cu(II) back to Cu(I) through charge transfer induced by near-infrared (NIR)-II photothermal energy, thereby effectively maintaining the enzyme-like activity of the nanozyme. Additionally, Cu9S8 is enhanced with a calcium sulfide (CaS) coating. This coating reacts in the acidic microenvironment of tumors to generate hydrogen sulfide (H2S) gas, which in turn suppresses the catalase activity inherent in tumor cells, ensuring a plentiful supply of H2O2 for the nanozyme's operation. This dual strategy of amplifying enzyme-like activity and substrate availability culminates in the generation of ample OH within tumor cells, leading to significant immunogenic cell death and thereby realizing potent immunotherapy.

Voltage-gated sodium channels in cancers.

Voltage-gated sodium channels (VGSCs) initiate action potentials in electrically excitable cells and tissues. Surprisingly, some VGSC genes are aberrantly expressed in a variety of cancers, derived from "non-excitable" tissues that do not generate classic action potentials, showing potential as a promising pharmacological target for cancer. Most of the previous review articles on this topic are limited in scope, and largely unable to provide researchers with a comprehensive understanding of the role of VGSC in cancers. Here, we review the expression patterns of all nine VGSC α-subunit genes (SCN1A-11A) and their four regulatory ß-subunit genes (SCN1B-4B). We reviewed data from the Cancer Genome Atlas (TCGA) database, complemented by an extensive search of the published papers. We summarized and reviewed previous independent studies and analyzed the VGSC genes in the TCGA database regarding the potential impact of VGSC on cancers. A comparison between evidence gathered from independent studies and data review was performed to scrutinize potential biases in prior research and provide insights into future research directions. The review supports the view that VGSCs play an important role in diagnostics as well as therapeutics of some cancer types, such as breast, colon, prostate, and lung cancer. This paper provides an overview of the current knowledge on voltage-gated sodium channels in cancer, as well as potential avenues for further research. While further research is required to fully understand the role of VGSCs in cancer, the potential of VGSCs for clinical diagnosis and treatment is promising.

1,3,6-Trigalloylglucose: A Novel Potent Anti-Helicobacter pylori Adhesion Agent Derived from Aqueous Extracts of Terminalia chebula Retz.

1,3,6-Trigalloylglucose is a natural compound that can be extracted from the aqueous extracts of ripe fruit of Terminalia chebula Retz, commonly known as "Haritaki". The potential anti-Helicobacter pylori (HP) activity of this compound has not been extensively studied or confirmed in scientific research. This compound was isolated using a semi-preparative liquid chromatography (LC) system and identified through Ultra-high-performance liquid chromatography-MS/MS (UPLC-MS/MS) and Nuclear Magnetic Resonance (NMR). Its role was evaluated using Minimum inhibitory concentration (MIC) assay and minimum bactericidal concentration (MBC) assay, scanning electron microscope (SEM), inhibiting kinetics curves, urea fast test, Cell Counting Kit-8 (CCK-8) assay, Western blot, and Griess Reagent System. Results showed that this compound effectively inhibits the growth of HP strain ATCC 700392, damages the HP structure, and suppresses the Cytotoxin-associated gene A (Cag A) protein, a crucial factor in HP infection. Importantly, it exhibits selective antimicrobial activity without impacting normal epithelial cells GES-1. In vitro studies have revealed that 1,3,6-Trigalloylglucose acts as an anti-adhesive agent, disrupting the adhesion of HP to host cells, a critical step in HP infection. These findings underscore the potential of 1,3,6-Trigalloylglucose as a targeted therapeutic agent against HP infections.

Flexocatalytic Reduction of Tumor Interstitial Fluid/Solid Pressure for Efficient Nanodrug Penetration.

The practical efficacy of nanomedicines for treating solid tumors is frequently low, predominantly due to the elevated interstitial pressure within such tumors that obstructs the penetration of nanomedicines. This increased interstitial pressure originates from both liquid and solid stresses related to an undeveloped vascular network and excessive fibroblast proliferation. To specifically resolve the penetration issues of nanomedicines for tumor treatment, this study introduces a holistic "dual-faceted" approach. A treatment platform predicated on the WS2/Pt Schottky heterojunction was adopted, and flexocatalysis technology was used to disintegrate tumor interstitial fluids, thus producing oxygen and reactive oxygen species and effectively mitigating the interstitial fluid pressure. The chemotherapeutic agent curcumin was incorporated to further suppress the activity of cancer-associated fibroblasts, minimize collagen deposition in the extracellular matrix, and alleviate solid stress. Nanomedicines achieve homologous targeting by enveloping the tumor cell membrane. It was found that this multidimensional strategy not only alleviated the high-pressure milieu of the tumor interstitium─which enhanced the efficiency of nanomedicine delivery─but also triggered tumor cell apoptosis via the generated reactive oxygen species and modulated the tumor microenvironment. This, in turn, amplified immune responses, substantially optimizing the therapeutic impacts of nanomedicines.

APR-246 increases tumor antigenicity independent of p53.

We previously reported that activation of p53 by APR-246 reprograms tumor-associated macrophages to overcome immune checkpoint blockade resistance. Here, we demonstrate that APR-246 and its active moiety, methylene quinuclidinone (MQ) can enhance the immunogenicity of tumor cells directly. MQ treatment of murine B16F10 melanoma cells promoted activation of melanoma-specific CD8+ T cells and increased the efficacy of a tumor cell vaccine using MQ-treated cells even when the B16F10 cells lacked p53. We then designed a novel combination of APR-246 with the TLR-4 agonist, monophosphoryl lipid A, and a CD40 agonist to further enhance these immunogenic effects and demonstrated a significant antitumor response. We propose that the immunogenic effect of MQ can be linked to its thiol-reactive alkylating ability as we observed similar immunogenic effects with the broad-spectrum cysteine-reactive compound, iodoacetamide. Our results thus indicate that combination of APR-246 with immunomodulatory agents may elicit effective antitumor immune response irrespective of the tumor's p53 mutation status.

MAPK signaling pathway-based glioma subtypes, machine-learning risk model, and key hub proteins identification.

An early diagnosis and precise prognosis are critical for the treatment of glioma. The mitogen­activated protein kinase (MAPK) signaling pathway potentially affects glioma, but the exploration of the clinical values of the pathway remains lacking. We accessed data from TCGA, GTEx, CGGA, etc. Up-regulated MAPK signaling pathway genes in glioma were identified and used to cluster the glioma subtypes using consensus clustering. The subtype differences in survival, cancer stemness, and the immune microenvironment were analyzed. A prognostic model was trained with the identified genes using the LASSO method and was validated with three external cohorts. The correlations between the risk model and cancer-associated signatures in cancer were analyzed. Key hub genes of the gene set were identified by hub gene analysis and survival analysis. 47% of the MAPK signaling pathway genes were overexpressed in glioma. Subtypes based on these genes were distinguished in survival, cancer stemness, and the immune microenvironment. A risk model was calculated with high confidence in the prediction of overall survival and was correlated with multiple cancer-associated signatures. 12 hub genes were identified and 8 of them were associated with survival. The MAPK signaling pathway was overexpressed in glioma with prognostic value.

Pan-cancer genetic analysis of disulfidptosis-related gene set.

BACKGROUND: A recent study has identified a novel programmed cell death pathway, termed disulfidptosis, which is based on disulfide proteins. This discovery provides new insight into the mechanisms of cell death and may have implications for therapeutic strategies targeting cell death pathways. This study aimed to evaluate the pan-cancer genomics and clinical association of disulfidptosis and disulfidptosis-related cell death genes, including SLC7A11, INF2, CD2AP, PDLIM1, ACTN4, MYH9, MYH10, IQGAP1, FLNA, FLNB, TLN1, MYL6, ACTB, DSTN, and CAPZB. METHODS: Using multi-omics profiling data, this study provides a comprehensive and systematic characterization of disulfidptosis genes across more than 9000 samples of over 30 types of cancer. RESULTS: FLNA and FLNB were the two most frequently mutated disulfidptosis cell death genes in cancer. UCEC and SKCM were the two cancer types that have the highest mutation rates while the mutation of ACTN4 was associated with worse survival of CESC and ESCA. Breast cancer was potentially affected by disulfidptosis because its subtypes are different in disulfidptosis gene expression. Similarly, KIRC might also be associated with disulfidptosis. Additionally, the association of disulfidptosis-related cell death genes with survival was analyzed, with MESO and LGG as the top cancer types with survival associated with disulfidptosis cell death genes. The correlation between CNV and survival across multiple cancer types found that UCEC, KIRP, LGG, and KIRC were the top cancer types where the CNV level was associated with survival. There was a negative correlation between expression and methylation for most of the genes and there was only a slight correlation between methylation levels and survival of cancer in LGG. About half of the disulfidptosis-related cell death proteins were associated with the activation of EMT. Disulfidptosis genes were correlated to immune cell infiltration levels in cancers. Multiple compounds were identified as potential drugs that might be affected by disulfidptosis-related cell death for future study. CONCLUSION: Disulfidptosis cell death genes are potentially involved in many cancer types and can be developed as candidates for cancer diagnosis, prognosis, and therapeutic biomarkers.

The Potential Effect of General Anesthetics in Cancer Surgery: Meta-Analysis of Postoperative Metastasis and Inflammatory Cytokines.

Metastasis or recurrence following curative surgery is the main indicator of tumor progress and is the main cause of patient death. For more than three decades, the potential for general anesthesia to affect cancer outcomes has been a subject of concern with considerable research interest. Here, we conducted this systematic review and meta-analysis to summarize the effect of inhalational anesthesia (IHNA) vs. propofol-based total intravenous anesthesia (TIVA) on metastasis and recurrence after cancer surgery from clinical and pre-clinical studies. The relative risk for metastasis/recurrence in TIVA is 0.61 (95% confidence interval (95% CI) 0.46 to 0.82, p = 0.0009) compared to IHNA. Inflammatory cytokines have been implicated in cancer metastasis following cancer surgery, thus we analyzed inflammatory cytokines levels after surgery under IHNA or TIVA. Based on pooled analysis, a lower IL-6 level was noticed in TIVA in comparison to IHNA (standardized mean difference (SMD) = 0.77, 95% CI = 0.097 to 1.44, I2 = 92%, p = 0.02) but not TNF-α or IL-10. Preclinical animal model studies show that inhalational anesthetics increase the risk of breast cancer metastasis compared to propofol. In conclusion, the current evidence suggests intravenous anesthetic propofol is associated with less metastasis/recurrence and lower postoperative IL-6 level over inhaled anesthetics in the oncological surgery. We urge more well-designed clinical and preclinical studies in this field.

Exploring the mechanism underlying hyperuricemia using comprehensive research on multi-omics.

Hyperuricemia involves multiple complex metabolisms, but no study has conducted a comprehensive analysis using human blood and urine metabolomics for hyperuricemia. Serum and urine samples from 10 patients with hyperuricemia and 5 controls were collected and analyzed by the UHPLC-MS/MS. Differential metabolites were identified and used in the enrichment analysis where we collected hyperuricemia target genes. Hyperuricemia kidney differential expressed genes (DEGs) were identified using RNA-sequencing data from the hyperuricemia mouse model induced by the potassium oxonate. A Mendelian randomization analysis of the association between caffeine-containing drinks and gout risk was conducted. An intersection analysis between hyperuricemia target genes and hyperuricemia kidney DEGs was conducted and the resulting genes were used for network analysis using the STRING. 227 differential metabolites were identified as differential metabolites and were enriched in 7 KEGG pathways, among which "Caffeine metabolism" was the top. The Mendelian randomization analysis revealed a significant association between tea or coffee intake and gout risk. There were 2173 genes that were identified as hyperuricemia kidney DEGs from mouse data. The intersection analysis identified 51 genes for the hyperuricemia regulation network. A hyperuricemia regulation protein network in the kidney was constructed. This study suggested a potential association between caffeine and hyperuricemia and constructed a hyperuricemia regulation network for future reference.

Research on Response Parameters and Classification Identification Method of Concrete Vibration Process.

The vibration process applied to fresh concrete is an important link in the construction process, but the lack of effective monitoring and evaluation methods results in the quality of the vibration process being difficult to control and, therefore, the structural quality of the resulting concrete structures difficult to guarantee. In this paper, according to the sensitivity of internal vibrators to vibration acceleration changes under different vibration media, the vibration signals of vibrators in air, concrete mixtures, and reinforced concrete mixtures were collected experimentally. Based on a deep learning algorithm for load recognition of rotating machinery, a multi-scale convolution neural network combined with a self-attention feature fusion mechanism (SE-MCNN) was proposed for medium attribute recognition of concrete vibrators. The model can accurately classify and identify vibrator vibration signals under different working conditions with a recognition accuracy of up to 97%. According to the classification results of the model, the continuous working times of vibrators in different media can be further statistically divided, which provides a new method for accurate quantitative evaluation of the quality of the concrete vibration process.

A bioinformatic study of IGFBPs in glioma regarding their diagnostic, prognostic, and therapeutic prediction value.

BACKGROUND: It is essential to develop better biomarkers for diagnosis, prediction, and treating glioma patients to ensure successful clinical outcomes. The clinical application of Insulin-Like Growth Factor Binding Proteins (IGFBPs) for glioma is yet to be investigated. METHODS: Cohorts were obtained from TCGA, GTEx, CGGA, HPA, Oncomine, CancerSEA, TISCH, etc. The expressions, methylation, and survival association of IGFBPs were analyzed. The Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to construct a prognostic model. The correlation of IGFBPs and immune cells or immune molecules was analyzed. The effect of IGFBPs on immune therapy and chemotherapy was analyzed. The top 500 correlated genes of IGFBPs were enriched in GO terms. Correlations between IGFBPs and functional states in glioma single-cells and correlations between IGFBPs and chemokines in samples were analyzed. RESULTS: IGFBPs were overexpressed in glioma. Malignant cells were the major cell types that expressed IGFBPs. Higher-grade glioma had a higher expression of IGFBPs, which were associated with worse survival. A survival model of IGFBPs for glioma patients was trained and validated. A nomogram was generated. Generally, IGFBPs mRNA expression was negatively correlated with B cells and T cells. IGFBPs were associated with multiple immune molecules and drug sensitivity. CONCLUSION: IGFBPs were powerful diagnostic, prognostic, and therapeutic prediction biomarkers for glioma.

Expression and potential immune involvement of cuproptosis in kidney renal clear cell carcinoma.

Cuproptosis is a newly identified programmed cell death pathway mediated by intracellular free copper. Cuproptosis genes were studied in this study for a better insight into the role of cuproptosis in cancers. The analysis identified kidney renal clear cell carcinoma (KIRC) as a cancer type most likely to be affected by cuproptosis. This study analyzed the multi-omic data to explore the cancer-noncancer expression pattern and potential immune involvement of the cuproptosis pathway in KIRC. This study clustered the TCGA KIRC samples based on the gene set of 12 cuproptosis genes to study the role of cuproptosis in the KIRC immune microenvironment and found the potential value of cuproptosis signature for immunotherapy prognosis. This study concluded that cuproptosis might affect KIRC and had potential application value in immune therapy. Hopefully, this study can contribute to the application of cuproptosis in the clinical therapy of KIRC.

A pan-cancer-bioinformatic-based literature review of TRPM7 in cancers.

TRPM7, a divalent cation-selective channel with kinase domains, has been widely reported to potentially affect cancers. In this study, we conducted multiple bioinformatic analyses based on open databases and reviewed articles that provided evidence for the effects of TRPM7 on cancers. The purposes of this paper are 1) to provide a pan-cancer overview of TRPM7 in cancers; 2) to summarize evidence of TRPM7 effects on cancers; 3) to identify potential future studies of TRPM7 in cancer. Bioinformatics analysis revealed that no cancer-related TRPM7 mutation was found. TRPM7 is aberrantly expressed in most cancer types but the cancer-noncancer expression pattern varies across cancer types. TRPM7 was not associated with survival, TMB, or cancer stemness in most cancer types. TRPM7 affected drug sensitivity and tumor immunity in some cancer types. The in vitro evidence, preclinical in vivo evidence, and clinical evidence for TRPM7 effects on cancers as well as TRPM7 kinase substrate and TRPM7-targeting drugs associated with cancers were summarized to facilitate comparison. We matched the bioinformatics evidence to literature evidence, thereby unveiling potential avenues for future investigation of TRPM7 in cancers. We believe that this paper will help orient research toward important and relevant aspects of the role of TRPM7 in cancers.

Potential roles of Cornichon Family AMPA Receptor Auxiliary Protein 4 (CNIH4) in head and neck squamous cell carcinoma.

BACKGROUND: It is of great clinical significance to discover novel biomarkers for neck squamous cell carcinoma (HNSCC) treatments. We discovered a potential cancer-related gene, Cornichon Family AMPA Receptor Auxiliary Protein 4 (CNIH4), that can be a biomarker for HNSCC. METHODS: We access multiple open databases and analyzed bulk mRNA-sequencing, protein staining, and single-cell mRNA-sequencing data of HNSCC and investigated the diagnostic and prognostic value of CNIH4 in HNSCC. The potential association between CNIH4 and the immune microenvironment of HNSCC was also estimated. RESULTS: CNIH4 was significantly up-regulated in HNSCC compared with non-cancer tissues. Higher CNIH4 resulted in a shorter overall survival time and we further constructed a survival nomogram for clinical applications. 2012 and 421 genes were identified as positive and negative differentially expressed genes of CNIH4 in HNSCC respectively. These genes were mostly mapped to "Cell cycle", "DNA replicate", "Cytokine-cytokine receptor interaction" KEGG pathways. Functions associated with CNIH4 were "stemness", "cell cycle", and "DNA repair" in single-cell data. CNIH4 potentially affected immune cell infiltration levels and cancer immune therapy. CONCLUSION: CNIH4 is a potential diagnostic and prognostic biomarker associated with cancer stemness and immunity in HNSCC.

Small-molecule allosteric inhibitors of GPX4.

Encouraged by the dependence of drug-resistant, metastatic cancers on GPX4, we examined biophysical mechanisms of GPX4 inhibition, which revealed an unexpected allosteric site. We found that this site was involved in native regeneration of GPX4 under low glutathione conditions. Covalent binding of inhibitors to this allosteric site caused a conformational change, inhibition of activity, and subsequent cellular GPX4 protein degradation. To verify this site in an unbiased manner, we screened a library of compounds and identified and validated that an additional compound can covalently bind in this allosteric site, inhibiting and degrading GPX4. We determined co-crystal structures of six different inhibitors bound in this site. We have thus identified an allosteric mechanism for small molecules targeting aggressive cancers dependent on GPX4.

Pan-cancer genetic analysis of cuproptosis and copper metabolism-related gene set.

Background: A recent paper has revealed a novel cell death pathway, cuproptosis, a programmed cell death based on copper. This study aimed to evaluate the pan-cancer genomics and clinical association of cuproptosis and copper metabolism-related cell death genes, including SLC25A3, SLC25A37, SLC31A1, FDX1, DLAT, LIAS, ATP7A, ATP7B, COX17, SCO1, SCO2, COX11, and COX19. Methods: By mining multi-omics profiling data, we performed a comprehensive and systematic characterization of cuproptosis genes across more than 9,000 samples of over 30 types of cancer. Results: ATP7B and ATP7A were the two most frequently mutated copper cell death genes in cancer. UCEC and SKCM were the two cancer types that have the highest mutation rates while the mutation of LIAS was associated with worse survival of BRCA. Brain cancer was potentially affected by copper cell death because of the difference in copper cell death gene expression among subtypes and stages. On the contrary, KIRC might have a lower cuproptosis activity because of the decrease in copper cell death gene expression. In lung cancer and kidney cancer, most of the cancer-noncancer expression patterns of copper cell death genes were consistent between mRNA and protein levels. Some of the cuproptosis gene expression was associated with the survival of LGG, KIRC, and ACC. The top five expression-copy numbers correlating cancer types were BRCA, OV, LUSC, HNSC, BLCA, and LUAD. Generally, the copy number variations of these genes in KIRC, UCEC, and LGG were associated with survival. The expression of DLAT, LIAS, and ATP7B was negatively correlated with the methylation in most of the cancer types. The copper cell death genes regulating miRNA and pathway regulation networks were constructed. The copper cell death genes were correlated with immune cell infiltration levels of multiple immune cells. These genes were correlated with the sensitivity of cancer cells to multiple drugs. Conclusion: Copper cell death genes are potentially involved in many cancer types and can be developed as candidates for cancer diagnosis, prognosis, and therapeutic biomarkers.

Pan-cancer profiles of the cuproptosis gene set.

A recent study has revealed a novel cell death pathway, called "cuproptosis", a programmed cell death based on copper. A total of 12 genes were involved in the cuproptosis pathway, including 7 pro-cuproptosis genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, and PDHB) genes, 3 anti-cuproptosis genes (MTF1, GLS, and CDKN2A), and 2 key copper transporters ATP7B and SLC31A1. The insight into these cuproptosis genes in cancer is necessary to understand cuproptosis-related tumorigenesis and to develop the cuproptosis pathway as a potential therapeutic target for clinical cancer treatment. By mining multi-omic profiling data, we performed a comprehensive and systematic characterization of the cuproptosis of these 12 genes across more than 9000 samples of 33 types of cancer. This letter not only revealed diverse mechanisms of the gene expression regulations of the cuproptosis gene set in cancer but also analyzed the potential associations between cuproptosis and other common cancer pathways, providing an overall picture of cuproptosis in cancer for future reference. This study comprehensively clarified the genomic pan-cancer profiles of the cuproptosis gene set regarding the SNV, CNV, methylation, mRNA expression, pathway cross-talk, and miRNA regulations across 33 solid tumors. Our findings revealed that genomic alterations and miRNA-mRNA network-mediated ectopic expression of cuproptosis genes were involved in the activation of other cancer-related pathways and also identified KIRC as a potential cancer type that might be affected by cuproptosis. We think, as the rase of the cuproptosis cancer research, these in-time profiles will provide a genetic overview and useful information for future studies on the cuproptosis in cancers.