Head and neck squamous cell carcinoma (HNSCC), the most common malignancy of the head and neck, has an overall 5-year survival rate of <50%. Genes associated with cuproptosis, a newly identified copper-dependent form of cell death, are aberrantly expressed in various tumours. However, their role in HNSCC remains unknown. In this study, bioinformatic analysis revealed that the cuproptosis-related gene CDKN2A was correlated with the malignant behaviour of HNSCC. Kaplan-Meier (KM) curves showed that patients with high CDKN2A expression had a better prognosis. Multiomic analysis revealed that CDKN2A may be associated with cell cycle and immune cell infiltration in the tumour microenvironment and is important for maintaining systemic homeostasis in the body. Furthermore, molecular docking and molecular dynamics simulations suggested strong binding between plicamycin and CDKN2A. And plicamycin inhibits the progression of HNSCC in cellular assays. In conclusion, this study elucidated a potential mechanism of action of the cuproptosis-associated gene CDKN2A in HNSCC and revealed that plicamycin targets CDKN2A to improve the prognosis of patients.
Retinoids, natural and synthetic derivatives of vitamin A, have many regulatory functions in human body, including regulating cellular proliferation, differentiation, apoptosis. Moreover, retinoids have been used successfully for the treatment of certain malignancies, especially acute promyelocytic leukemia (APL) in adults and neuroblastoma in children. However, retinoids have not yet been translated into effective systemic treatments for most solid cancers. Some recent studies have shown that retinoids promote tumorigenesis. Therefore, we performed this meta-analysis to systematically evaluate the efficacy of retinoids in the chemoprevention and treatment of cancers. We performed literature search of several electronic databases, including PubMed, Embase and Cochrane Library from 2000 January to 2021 November. Various outcomes were applied to investigate the potential of retinoids for prevention and treatment of cancers. The primary outcomes in this study were disease recurrence and clinical response. The secondary outcomes included overall survival (OS), cancer development, disease progression and event-free survival. We identified 39 randomized controlled trials with 15,627 patients in this study. Our results showed that lower recurrence rate and better clinical response were obtained in retinoids treated patients with cancer or premalignancy as compared with control. The differences were statistically significant (RR = 0.85, 95% CI = 0.74–0.96, p = 0.01; RR = 1.24, 95% CI = 1.03–1.49, p = 0.02, respectively). Retinoids treatment was not associated with improvement in overall survival, cancer development, disease progression or event-free survival. Subgroup analysis conducted based on cancer type showed that patients benefited from retinoids treatment in APL, renal cell carcinoma, hepatocellular carcinoma, lung cancer, Kaposi sarcoma, and complete hydatidiform mole. No significant therapeutic effect was noted in head and neck cancer, acute myeloid leukemia (AML), melanoma, breast cancer, bladder cancer, cervical intraepithelial neoplasia (CIN) or cervical carcinoma. Subgroup analysis based on tumor classification demonstrated that retinoids group obtained a lower recurrence rate and better clinical response than control group in solid cancers. In conclusion, clinical application of retinoids was associated with reduction in disease recurrence and improvement in clinical response, illustrating that retinoids play a key role in cancer prevention and therapy. Further research is needed to broaden the utility of retinoids in other types of cancers.
Systematic Review Registration: PROSPERO, identifier CRD42022296706.
As a key copper homeostasis-related molecule, lipoyltransferase 1 (LIPT1) is an essential enzyme for the activation of mitochondrial 2-ketoacid dehydrogenase, participating in fatty acylation. However, the biological significances of LIPT1 in the pan-cancer are unclear. Here, we comprehensively analyzed the functional characteristics of LIPT1 in human cancers and its roles in immune response. We found that LIPT1 was down-regulated in some cancers. And LIPT1 overexpression is associated with favorable prognosis in these patients, such as breast cancer, clear cell renal cell carcinoma, ovarian cancer and gastric cancer. We also explored the mutational status and methylation levels of LIPT1 in human cancers. Gene enrichment analysis indicated that abnormally expressed LIPT1 was significantly associated with immune cells infiltration, such as B cells, CD8+ T cells and cancer-associated fibroblast cells. The result from single cell sequencing reflected the important roles of LIPT1 in the regulation of several biological behaviors of cancer cells, such as DNA damage response and cell apoptosis. Taken together, our research could provide a comprehensive overview about the significances of LIPT1 in human pan-cancer progression, prognosis and immune.
Osteosarcoma (OS) is a common bone cancer in children and adolescents, and metastasis and recurrence are the major causes of poor treatment outcomes. A better understanding of the tumor microenvironment is required to develop an effective treatment for OS. In this paper, a single-cell RNA sequencing dataset was taken to a systematic genetic analysis, and potential signaling pathways linked with osteosarcoma development were explored. Our findings revealed 25 clusters across 11 osteosarcoma tissues, with 11 cell types including “Chondroblastic cells”, “Osteoblastic cells”, “Myeloid cells”, “Pericytes”, “Fibroblasts”, “Proliferating osteoblastic cells”, “Osteoclasts”, “TILs”, “Endothelial cells”, “Mesenchymal stem cells”, and “Myoblasts”. The results of Cell communication analysis showed 17 potential cellular communication networks including “COLLAGEN signaling pathway network”, “CD99 signaling pathway network”, “PTN signaling pathway network”, “MIF signaling pathway network”, “SPP1 signaling pathway network”, “FN1 signaling pathway network”, “LAMININ signaling pathway network”, “FGF signaling pathway network”, “VEGF signaling pathway network”, “GALECTIN signaling pathway network”, “PERIOSTIN signaling pathway network”, “VISFATIN signaling pathway network”, “ITGB2 signaling pathway network”, “NOTCH signaling pathway network”, “IGF signaling pathway network”, “VWF signaling pathway network”, “PDGF signaling pathway network”. This research may provide novel insights into the pathophysiology of OS’s molecular processes.
Frontiers in Nutrition
Food and Nutrition Security: Underutilized Plant and Animal-Based Foods