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Background: Intracellular copper homeostasis requires a complex system. It has shown considerable prospects for intervening in the tumor microenvironment (TME) by regulating copper homeostasis and provoking cuproptosis. Their relationship with hepatocellular carcinoma (HCC) remains elusive. Methods: In TCGA and ICGC datasets, LASSO and multivariate Cox regression were applied to obtain the signature on the basis of genes associated with copper homeostasis and cuproptosis. Bioinformatic tools were utilized to reveal if the signature was correlated with HCC characteristics. Single-cell RNA sequencing data analysis identified differences in tumor and T cells' pathway activity and intercellular communication of immune-related cells. Real-time qPCR analysis was conducted to measure the genes' expression in HCC and adjacent normal tissue from 21 patients. CCK8 assay, scratch assay, transwell, and colony formation were conducted to reveal the effect of genes on in vitro cell proliferation, invasion, migration, and colony formation. Results: We constructed a five-gene scoring system in relation to copper homeostasis and cuproptosis. The high-risk score indicated poor clinical prognosis, enhanced tumor malignancy, and immune-suppressive tumor microenvironment. The T cell activity was markedly reduced in high-risk single-cell samples. The high-risk HCC patients had a better expectation of ICB response and reactivity to anti-PD-1 therapy. A total of 156 drugs were identified as potential signature-related drugs for HCC treatment, and most were sensitive to high-risk patients. Novel ligand-receptor pairs such as FASLG, CCL, CD40, IL2, and IFN-γ signaling pathways were revealed as cellular communication bridges, which may cause differences in TME and immune function. All crucial genes were differentially expressed between HCC and paired adjacent normal tissue. Model-constructed genes affected the phosphorylation of mTOR and AKT in both Huh7 and Hep3B cells. Knockdown of ZCRB1 impaired the proliferation, invasion, migration, and colony formation in HCC cell lines. Conclusion: We obtained a prognostic scoring system to forecast the TME changes and assist in choosing therapy strategies for HCC patients. In this study, we combined copper homeostasis and cuproptosis to show the overall potential risk of copper-related biological processes in HCC for the first time. [ABSTRACT FROM AUTHOR]

Background: Early identification of patients who will benefit from immune checkpoint inhibitors (ICIs) has recently become a hot issue in cancer immunotherapy. Peripheral cytokines are key regulators in the immune system that can induce the expression of immune checkpoint molecules; however, the association between peripheral cytokines and the efficiency of ICIs remains unclear. Methods: A systematic review was conducted in several public databases from inception through 3 February 2022 to identify studies investigating the association between peripheral cytokines (i.e., IL-1β, IL-2, IL-2RA, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, IFN-γ, and TGF-β) and ICI treatment. Survival data, including overall survival (OS) and/or progression-free survival (PFS), were extracted, and meta-analyses were performed. Results: Twenty-four studies were included in this analysis. The pooled results demonstrated that the pretreatment peripheral levels of IL-6 (univariate analysis: HR = 2.53, 95% CI = 2.21-2.89, p < 0.00001; multivariate analysis: HR = 2.21, 95% CI = 1.67-2.93, p < 0.00001) and IL-8 (univariate analysis: HR = 2.17, 95% CI = 1.98-2.38, p < 0.00001; multivariate analysis: HR = 1.88, 95% CI= 1.70-2.07, p < 0.00001) were significantly associated with worse OS of cancer patients receiving ICI treatment in both univariate and multivariate analysis. However, high heterogeneity was found for IL-6, which might be attributed to region, cancer type, treatment method, sample source, and detection method. Conclusion: The peripheral level of IL-8 may be used as a prognostic marker to identify patients with inferior response to ICIs. More high-quality prospective studies are warranted to assess the predictive value of peripheral cytokines for ICI treatment. [ABSTRACT FROM AUTHOR]

Okadaic acid (OA) is produced by Dinophysis and Prorocentrum dinoflagellates and primarily accumulates in bivalves, and this toxin has harmful effects on consumers and operators. In this work, we first report the use of aptamers as novel non-toxic probes capable of binding to a monoclonal antibody against OA (OA-mAb). Aptamers that mimic the OA toxin with high affinity and selectivity were generated by the magnetic bead-assisted systematic evolution of ligands by exponential enrichment (SELEX) strategy. After 12 selection rounds, cloning, sequencing and enzyme-linked immunosorbent assay (ELISA) analysis, four candidate aptamers (O24, O31, O39, O40) were selected that showed high affinity and specificity for OA-mAb. The affinity constants of O24, O31, O39 and O40 were 8.3 × 108 M-1, 1.47 × 109 M-1, 1.23 × 109 M-1 and 1.05 × 109 M-1, respectively. Indirect competitive ELISA was employed to determine the internal-image function of the aptamers. The results reveal that O31 has a similar competitive function as free OA toxin, whereas the other three aptamers did not bear the necessary internal-image function. Based on the derivation of the curvilinear equation for OA/O31, the equation that defined the relationship between the OA toxin content and O31 was Y = 2.185X - 1.78. The IC50 of O31 was 3.39 ng.mL-1, which was close to the value predicted by the OA ELISA (IC50 = 4.4 ng.mL-1); the IC10 was 0.33 ng.mL-1. The above data provides strong evidence that internal-image functional aptamers could be applicable as novel probes in a non-toxic assay. [ABSTRACT FROM AUTHOR]