A cuproptosis-related lncRNA signature for predicting prognosis and immunotherapy response of lung adenocarcinoma

Abstract Background Copper-induced cell death (cuproptosis) is a new regulatory cell death mechanism. Long noncoding RNAs (lncRNAs) are related to tumor immunity and metastasis. However, the correlation of cuproptosis-related lncRNAs with the immunotherapy response and prognosis of lung adenocarcinoma (LUAD) patients is not clear. Methods We obtained the clinical characteristics and transcriptome data from TCGA-LUAD dataset (containing 539 LUAD and 59 paracancerous tissues). By utilizing LASSO-penalized Cox regression analysis, we identified a prognostic signature composed of cuproptosis-related lncRNAs. This signature was then utilized to segregate patients into two different risk categories based on their respective risk scores. The identification of differentially expressed genes (DEGs) between high- and low-risk groups was carried out using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We evaluated the immunotherapy response by analyzing tumor mutational burden (TMB), immunocyte infiltration and Tumor Immune Dysfunction and Exclusion (TIDE) web application. The "pRRophetic" R package was utilized to conduct further screening of potential therapeutic drugs for their sensitivity. Results We ultimately identified a prognostic risk signature that includes six cuproptosis-related lncRNAs (AP003778.1, AC011611.2, CRNDE, AL162632.3, LY86-AS1, and AC090948.1). Compared with clinical characteristics, the signature was significantly correlated with prognosis following the control of confounding variables (HR = 2.287, 95% CI = 1.648–3.174, p ˂ 0.001), and correctly predicted 1-, 2-, and 3-year overall survival (OS) rates (AUC value = 0.725, 0.715, and 0.662, respectively) in LUAD patients. In terms of prognosis, patients categorized as low risk exhibited more positive results in comparison to those in the high-risk group. The enrichment analysis showed that the two groups had different immune signaling pathways. Immunotherapy may offer a more appropriate treatment option for high-risk patients due to their higher TMB and lower TIDE scores. The higher risk score may demonstrate increased sensitivity to bexarotene, cisplatin, epothilone B, and vinorelbine. Conclusions Based on cuproptosis-related lncRNAs, we constructed and validated a novel risk signature that may be used to predict immunotherapy efficacy and prognosis in LUAD patients

Aldehyde dehydrogenase 2 polymorphism is associated with chemotherapy‐related cognitive impairment in patients with breast cancer who receive chemotherapy

Abstract Background Chemotherapy‐related cognitive impairment (CRCI) is a common but easily overlooked condition that markedly affects the quality of life (QOL) of patients with breast cancer. The rs671 is a common gene polymorphism of aldehyde dehydrogenase 2 (ALDH2) in Asia that is involved in aldehyde metabolism and may be closely related to CRCI. However, no study has yet summarised the association between ALDH2 and CRCI. Methods This study enrolled one hundred and twenty‐four patients diagnosed with breast cancer according to the pathology results, genotyped for ALDH2 single‐nucleotide polymorphisms (SNP) to explore these. The mini‐mental state exam (MMSE), verbal fluency test (VFT), and digit span test (DST) results were compared in these patients before and after chemotherapy (CT). Results We found that patients with ALDH2 gene genotypes of rs671_GG, rs886205_GG, rs4648328_CC, and rs4767944_TT polymorphisms were more likely to suffer from cognitive impairment during chemotherapy. A trend toward statistical significance was observed for rs671_GG of DST (z = 2.769, p = 0.006), VFT (t = 4.624, P<0.001); rs886205_GG of DST (z = 3.663, P<0.001); rs4648328_CC of DST (z = 2.850, p = 0.004), VFT (t = 3.477, p = 0.001); and rs4767944_TT of DST (z = 2.967, p = 0.003), VFT (t = 2.776, p = 0.008). The cognitive indicators of these patients significantly decreased after chemotherapy (p < 0.05). The difference in ALDH2 rs671 was most obvious. Conclusion Our results showed what kinds of ALDH2 genotyped patients that are more likely to develop CRCI. In the future, it may be possible to infer the risk of CRCI by detecting the single‐nucleotide locus of ALDH2 that is conducive to strengthening clinical interventions for these patients and improving their QOL. More importantly, this study has important implications for Asian women with breast cancer as ALDH2 rs671 is a common polymorphism in Asians

Effects of Managing Cancer and Living Meaningfully on Cancer-Related Fatigue and Cytokine Levels in Gastrointestinal Cancer Patients

Objective: To evaluate the effects of managing cancer and living meaningfully (CALM), a psychological intervention with semi-structured interviews, on cancer-related fatigue (CRF), quality of life (QOL), and sleep quality in patients with gastrointestinal (GI) cancer, which may be accompanied by changes in cytokine levels. Methods: A total of 152 GI cancer patients with CRF were enrolled in the study during treatment. Patients were randomly assigned to CALM or usual care (UC) groups. Patients in the CALM group received 12 weeks of CALM plus usual care, and patients in the UC group received usual care plus usual health education. All study participants were evaluated at baseline and at 12 weeks using the Revised Piper Fatigue Scale, the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire-Core 30, and the Pittsburgh Sleep Quality Index scale, while cytokine levels were measured. Results: At 12 weeks, the differences in total CRF, QOL, sleep quality, IL-6, IL-4, and TNF-α levels were statistically significant not only in the CALM group compared to patients in the UC group ( t  = −7.902, t  = 2.163, t  = −2.187, t  = 3.313, t  = −4.120, t  = −3.853, respectively; P  < .05), but also in the CALM group compared to baseline ( t  = 11.331, t  = −5.492, t  = 5.450, t  = −2.418, t  = 2.186, t  = 2.699, respectively; P  < .05). Additionally, the total CRF at 12 weeks was correlated with IL-4, IL-6, and TNF-α levels ( r  = −.30, r  = .31, r  = .32, respectively; P  < .001). Conclusions: CALM alleviated CRF and improved QOL and sleep quality in patients with GI cancer, and these improvements were accompanied by changes in IL-4, IL-6, and TNF-α levels

Chrysin protects against cerebral ischemia-reperfusion injury in hippocampus via restraining oxidative stress and transition elements

Chrysin is a natural flavonoid compound that has antioxidant and neuroprotective effects. Cerebral ischemia reperfusion (CIR) is closely connected with increased oxidative stress in the hippocampal CA1 region and homeostasis disorder of transition elements such as iron (Fe), copper (Cu) and zinc (Zn). This exploration was conducted to elucidate the antioxidant and neuroprotective effects of chrysin based on transient middle cerebral artery occlusion (tMCAO) in rats. Experimentally, sham group, model group, chrysin (50.0 mg/kg) group, Ginaton (21.6 mg/kg) group, Dimethyloxallyl Glycine (DMOG, 20.0 mg/kg) + chrysin group and DMOG group were devised. The rats in each group were performed to behavioral evaluation, histological staining, biochemical kit detection, and molecular biological detection. The results indicated that chrysin restrained oxidative stress and the rise of transition element levels, and regulated transition element transporter levels in tMCAO rats. DMOG activated hypoxia-inducible factor-1 subunit alpha (HIF-1α), reversed the antioxidant and neuroprotective effects of chrysin, and increased transition element levels. In a word, our findings emphasize that chrysin plays a critical role in protecting CIR injury via inhibiting HIF-1α against enhancive oxidative stress and raised transition metal levels