The prognostic value and immune landscape of a cuproptosis-related lncRNA signature in head and neck squamous cell carcinoma

Abstract

Background: Cuproptosis has been recognized as a novel regulatory cell death, which has been confirmed to promote the occurrence and development of tumors. However, whether cuproptosis-related lncRNA has an impact on the prognosis of squamous cell carcinoma of the head and neck (HNSCC) is still unclear.Methods: In total, 501 HNSCC tumor samples and 44 normal were downloaded from the TCGA database. Cuproptosis-related lncRNAs were obtained by co-expressed analysis. We got prognostic lncRNA that was associated with cuproptosis by using univariate Cox regression analysis and LASSO Cox regression. Then we constructed and validated the prognostic signature of HNSCC and analyzed the immune landscape of the signature.Results: The Prognostic Signature is based on 10 cuproptosis-related lncRNAs including AC090587.1, AC004943.2, TTN-AS1, AL162458.1, AC106820.5, AC012313.5, AL132800.1, WDFY3-AS2, CDKN2A-DT, and AL136419.3. The results of overall survival, risk score distribution, and survival status in the low-risk group were better than those in the high-risk group. In addition, all immune checkpoint genes involved were significantly different between the two risk groups (p < 0.05). The risk score was positively correlated with Eosinophils. M0 and M2 phenotype macrophages, mast cells activated, NK cells activated, and negatively related with B cells naive, mast cells resting, plasma cells, CD8T cells, T cells follicular helper, T cells regulatory (Tregs). Consensus clustering was identified in molecular subtypes of HNSC. More high-risk samples concentrated in Cluster1, which had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score and Single Nucleotide Polymorphisms (SNP) alternation than Cluster2.Conclusion: Our study elucidated the correlation between cuproptosis-related lncRNA with prognosis and immune landscape of HNSCC, which may provide references for further research on the exploration of the mechanism and functions of the prognosis for HNSCC.

Prognostic prediction of head and neck squamous cell carcinoma: Construction of cuproptosis‐related long non‐coding RNA signature

“…We observed that cuproptosis was closely associated with KLF3‐AS1and LINC01063. CDKN2A‐DT and AC090587.1 had been reported could act as cuproptosis‐related biomarkers in HNSCC, 40 , 41 which was consistent with our findings. However, compare with the signatures with eight or more cuproptosis‐related lncRNAs, our algorithms with six cuproptosis‐related lncRNAs were simpler and easier for verification in the future applications.…”

“…32 Mao et al 33 reported that KLF3-AS1 present in the exosomes secreted from human mesenchymal stem cells could help reduce the extent of pyroptosis in cardiomyocytes and improve myocardial infarction by exploiting the miR-138-5p/Sirt1 axis. LINC01063 was associated with ferroptosis [34][35][36] and autophagy [37][38][39] CDKN2A-DT and AC090587.1 had been reported could act as cuproptosis-related biomarkers in HNSCC, 40,41 which was consistent with our findings. However, compare with the signatures with eight or more cuproptosis-related lncRNAs, our algorithms with six cuproptosis-related lncRNAs were simpler and easier for verification in the future applications.…”

Cuproptosis-associated CDKN2A is targeted by plicamycin to regulate the microenvironment in patients with head and neck squamous cell carcinoma

“…We downloaded the small molecule structures from Drug Bank ( http://www.drugbank.com/ ) in SDF format ( Luo et al, 2022b ). In RDKit, the Experimental-Torsion Basic Knowledge Distance Geometry (ETKDG) algorithm was used to generate 3D conformations based on the modified distance geometry algorithm, while the MMFF94 stand was used to optimize small molecule structure and energy using the MMFFOptimize Molecule module ( Li et al, 2022 ).…”

“…In melanoma, lung cancer, and renal clear cell carcinoma, cuproptosis-related genes have been studied. In recent studies, researchers examined ten cuproptosis-related lncRNAs associated with immune function and prognosis in HNSCC ( Li et al, 2022 ). However, the functions and mechanisms of action of cuproptosis-related genes in HNSCC warrant further investigation.…”

Identification and validation of a novel cuproptosis-related genes signature associated with prognosis, clinical implications and immunotherapy of hepatocellular carcinoma

“…Emerging evidence also suggests crosstalk between curoprotosis and the tumor immune microenvironment (TME) ( Lv et al, 2022 )- ( Li et al, 2022a ). The tumor microenvironment plays a crucial role in cancer development and clinical outcomes ( Wu and Dai, 2017 ).…”