Tumor cuproptosis and immune infiltration improve survival of patients with hepatocellular carcinoma with a high expression of ferredoxin 1

BackgroundCuproptosis is a novel cell death pathway dependent on cellular copper ions and ferredoxin 1 (FDX1). Hepatocellular carcinoma (HCC) is derived from healthy liver as a central organ for copper metabolism. It remains no conclusive evidence whether cuproptosis is involved in survival improvement of patients with HCC.MethodA 365–liver hepatocellular carcinoma (LIHC) cohort with RNA sequencing data and paired clinical and survival information was obtained from the The Cancer Genome Atlas (TCGA) dataset. A retrospective cohort of 57 patients with HCC with stages I/II/III was collected by Zhuhai People’s Hospital from August 2016 to January 2022. Low- or high-FDX1 groups were divided according to the median value of FDX1 expression. Cibersort, single-sample gene set enrichment analysis, and multiplex immunohistochemistry analyzed immune infiltration in LIHC and HCC cohorts. Cell proliferation and migration of HCC tissues and hepatic cancer cell lines were evaluated using the Cell Counting Kit-8. Quantitative real-time PCR and RNA interference measured and downregulated FDX1 expression. Statistical analysis was conducted by R and GraphPad Prism software.ResultsHigh FDX1 expression significantly enhanced survival of patients with LIHC from the TCGA dataset, which was also demonstrated through a retrospective cohort with 57 HCC cases. Immune infiltration was different between the low– and high–FDX1 expression groups. Natural killer cells, macrophages, and B cells were significantly enhanced, and PD-1 expression was low in the high-FDX1 tumor tissues. Meanwhile, we found that a high expression of FDX1 decreased cell viability in HCC samples. HepG2 cells with FDX1 expression are sensitive to Cu2+, and interference of FDX1 promoted proliferation and migration of tumor cells. The consistent results were also demonstrated in Hep3B cells.ConclusionThis study reveals that cuproptosis and tumor immune microenvironment were together involved in improvement of survival in patients with HCC with a high expression of FDX1

Commissioning of the ArDM experiment at the Canfranc underground laboratory: First steps towards a tonne-scale liquid argon time projection chamber for Dark Matter searches

The Argon Dark Matter (ArDM) experiment consists of a liquid argon (LAr) time projection chamber (TPC) sensitive to nuclear recoils, resulting from scattering of hypothetical Weakly Interacting Massive Particles (WIMPs) on argon targets. With an active target mass of 850 kg ArDM represents an important milestone towards developments for large LAr Dark Matter detectors. Here we present the experimental apparatus currently installed underground at the Laboratorio Subterráneo de Canfranc (LSC), Spain. We show data on gaseous or liquid argon targets recorded in 2015 during the commissioning of ArDM in single phase at zero E-field (ArDM Run I). The data confirms the overall good and stable performance of the ArDM tonne-scale LAr detector.ISSN:1475-751

Backgrounds and pulse shape discrimination in the ArDM liquid argon TPC

The ArDM experiment completed a single-phase commissioning run (ArDM Run I) with an active liquid argon target of nearly one tonne in mass. The analysis of the data and comparison to predictions from full detector simulations allowed extraction of the detector properties and an assessment of the low background conditions. The 39Ar specific activity from the employed atmospheric argon is measured to be (0.95±0.05) Bq/kg. The cosmic muon flux at the Canfranc underground site was determined to be in the range (2–3.5)× 10−3m−2s−1. The statistical rejection power for electronic recoil events using the pulse shape discrimination method was estimated using a 252Cf neutron calibration source. Electronic and nuclear recoil band profiles were found to be well described by Gaussian distributions. Employing such a model we derive values for the electronic recoil statistical rejection power of more than 108 in the tonne-scale liquid argon target for events with more than 50 detected photons at a 50% acceptance for nuclear recoils. The 222Rn emanation rate of the ArDM cryostat at room temperature was found to be (65.6±0.4) μHz/l. These results represent an important physics milestone for the next run in the double-phase mode and in the context of foreseen developments towards the use of depleted argon targets.ISSN:1475-751