An original cuproptosis-related genes signature effectively influences the prognosis and immune status of head and neck squamous cell carcinoma

Abstract

Background: Recently, a non-apoptotic cell death pathway that is dependent on the presence of copper ions was proposed, named as cuproptosis. Cuproptosis have been found to have a strong association with the clinical progression and prognosis of several cancers. Head and neck squamous cell carcinoma (HNSC) are among the most common malignant tumors, with a 5-year relative survival rate ranging between 40% and 50%. The underlying mechanisms and clinical significance of cuproptosis-related genes (CRGs) in HNSC progression have not been clarified.Methods: In this study, expression pattern, biological functions, Immunohistochemistry (IHC), gene variants and immune status were analyzed to investigate the effects of CRGs on HNSC progression. Moreover, a 12-CRGs signature and nomogram were also constructed for prognosis prediction of HNSC.Results: The results revealed that some CRGs were dysregulated, had somatic mutations, and CNV in HNSC tissues. Among them, ISCA2 was found to be upregulated in HNSC and was strongly correlated with the overall survival (OS) of HNSC patients (HR = 1.13 [1.01–1.26], p-value = 0.0331). Functionally, CRGs was mainly associated with the TCA cycle, cell cycle, iron-sulfur cluster assembly, p53 signaling pathway, chemical carcinogenesis, and carbon metabolism in cancer. A 12-CRGs signature for predicting the OS was constructed which included, CAT, MTFR1L, OXA1L, POLE, NTHL1, DNA2, ATP7B, ISCA2, GLRX5, NDUFA1, and NDUFB2. This signature showed good prediction performance on the OS (HR = 5.3 [3.4–8.2], p-value = 3.4e-13) and disease-specific survival (HR = 6.4 [3.6–11], p-value = 2.4e-10). Furthermore, 12-CRGs signature significantly suppressed the activation of CD4+ T cells and antigen processing and presentation. Finally, a nomogram based on a 12-CRGs signature and clinical features was constructed which showed a significantly adverse effect on OS (HR = 1.061 [1.042–1.081], p-value = 1.6e-10) of HNSC patients.Conclusion: This study reveals the association of CRGs with the progression of HNSC based on multi-omics analysis. The study of CRGs is expected to improve clinical diagnosis, immunotherapeutic responsiveness and prognosis prediction of HNSC.

Construction of a novel disulfidptosis-related lncRNAs signature for prognosis prediction and anti-tumor immunity in laryngeal squamous cell carcinoma

“…KM survival analysis revealed notable survival disparities among patients with divergent risk scores. AUC-Curve of all LSCC patients verified the strong predictive ability of the 5-DRlncRNAs signature (the AUC value at 1, 3, and 5 years was 0.724, 0.836, and 0.809, respectively), which surpassed some of the existing models [ [33] , [34] , [35] ]. PCA further supported the disulfidptosis-related lncRNAs signature's ablities in differentiating high-risk from low-risk groups.…”

Association of abnormal NDUFB2 and UQCRH expression with venous thromboembolism in patients with liver cirrhosis

“…Functionally, copper death-related genes may be associated with a variety of cancers. [ 23 ] Studies by Hashime Sawai et al have shown that NDUFB2 is the key gene of mitochondrial oxidative phosphorylation and participates in the occurrence and development of bipolar disorder through mitochondrial oxidative phosphorylation. [ 24 ] Oxidative phosphorylation plays a key role in regulation of cell and tissue metabolism, some studies have shown that the regulation of oxidative phosphorylation can inhibit in flammation.…”

Integrated bioinformatic analysis of mitochondrial metabolism-related genes in acute myeloid leukemia

“…Venetoclax + azacytidine treatment can inhibit SDHA glutathionylation and target LSCs in AML patients ( 72 ). NDUFA1, subunit of mitochondrial complex I, was associated with the prognosis of head and neck squamous cell carcinoma ( 73 ). ECHS1 plays an important role in phospholipid metabolism, tumor occurrence, development, and drug resistance ( 74 ).…”