BackgroundACO1 and IREB2 are two homologous cytosolic regulatory proteins, which sense iron levels and change iron metabolism–linked molecules. These two genes were noticeably decreased in kidney renal clear cell carcinoma (KIRC), which confer poor survival. Meanwhile, there is a paucity of information about the mechanisms and clinical significance of ACO1 and IREB2 downregulation in renal cancers.MethodsThe expression profiles of ACO1 and IREB2 were assessed using multiple public data sets via several bioinformatics platforms. Clinical and pathological information was utilized to stratify cohorts for comparison. Patient survival outcomes were evaluated using the Kaplan–Meier plotter, a meta-analysis tool. The correlations of ACO1 and IREB2 with ferroptosis were further evaluated in The Cancer Genome Atlas (TCGA)–KIRC database. Tumor immune infiltration was analyzed using the CIBERSORT, TIMER, and GEPIA data resources. ACO1 antagonist sodium oxalomalate (OMA) and IREB2 inhibitor sodium nitroprusside (SNP) was used to treat renal cancer ACHN cells together with sorafenib.ResultsKIRC patients with low ACO1 or IREB2 contents exhibited a remarkably worse survival rate in contrast with those with high expression in Kaplan–Meier survival analyses. Meanwhile, ACO1 and IREB2 regulate autophagy-linked ferroptosis along with immune cell invasion in the tumor microenvironment in KIRC patients. Blocking the activation of these two genes by their inhibitors OMA and SNP ameliorated sorafenib-triggered cell death, supporting that ACO1 and IREB2 could be participated in its cytotoxic influence on renal cancer cells.ConclusionACO1 and IREB2 downregulation in renal cancers were correlated with cancer aggressiveness, cellular iron homeostasis, cytotoxic immune cell infiltration, and patient survival outcomes. Our research is integral to verify the possible significance of ACO1 and IREB2 contents as a powerful signature for targeted treatment or novel immunotherapy in clinical settings.
Background: Breast cancer has become the most common malignancy worldwide. Experimental and, retrospective, clinical data indicate that anaesthetic technique might influence the risk of metastasis after cancer surgery by modulating the immune system. The purpose of this study is to investigate the effect of perioperative lidocaine injection on immune cells such as T lymphocytes and natural killer cells (NK cells) and the quality of postoperative recovery in breast cancer patients and to propose new ideas and relevant theoretical evidence for the selection of anesthetic protocols for perioperative tumor patients.Methods: Women (n=68) undergoing primary breast tumour resection were randomly assigned to received 2% lidocaine (n=34; group L) or placebo (normal saline; n=34; group S). Venous blood was collected thirty minutes before surgery (T0), after tumor removal (T1), immediately after surgery (T2), 24 h after surgery (T3), and 48 h after surgery (T4). The percentages of NK cells and T lymphocyte subsets (CD3 + , CD4 + , CD8 + , CD4 + /CD8 + ) in peripheral blood were detected by flow cytometry. Patients' quality of recovery-15 (QoR-15) scores were recorded by questionnaire before and 24 h after the operation, as well as intraoperative propofol and remifentanil dosages, the frequency of 24 h postoperative remedial analgesia, and the incidence of nausea and vomiting, dizziness, and chest tightness.Results: There were 62 patients included in the study, and 60 patients were finally analyzed. The difference in the changing trend of NK cell levels in the 2 groups over time was statistically significant (F=7.675, P=0.008). The intraoperative changing trends of CD3 + T cells, CD4 + T cells, and the CD4 + /CD8 + ratio over time differed significantly between the 2 groups of patients (P<0.05), whereas the trends of CD8 + T cells did not differ significantly (P>0.05). The QoR-15 score at 24 h after surgery was higher in Group L (128.50±20.25) than in Group S (117.50±19.50), and the difference was statistically significant (P=0.005).No adverse events such as cardiac arrhythmia and lidocaine toxicity occurred in both groups during the perioperative period.Conclusions: Continuous intravenous pumping of lidocaine during the perioperative period has little effect on immune function in breast cancer patients and promotes postoperative recovery.
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