Journal: Translational Cancer Research

Article Title: Quetiapine inhibits the oxidative phosphorylation in head and neck squamous cell carcinoma through suppressing NAT10-mediated ac4C modification

doi: 10.21037/tcr-2025-1-2683

Figure Lengend Snippet: The expression of NAT10 in various tumors. A comparison of NAT10 mRNA expression in diverse human cancers versus unpaired (A) or paired (B) normal tissues, utilizing data sourced from the TCGA database. The red boxes represent the mRNA expression of NAT10 in HNSCC versus unpaired or paired normal tissues, respectively. Data are presented as mean ± SD. ns, no significance; *, P<0.05; **, P<0.01; ***, P<0.001 by unpaired t -test (A) and paired t -test (B). ACC (normal =0, tumor =79), BLCA (normal =19, tumor =412), BRCA (normal =113, tumor =1113), CESC (normal =3, tumor =306), CHOL (normal =9, tumor =35), COAD (normal =41, tumor =480), DLBC (normal =0, tumor =48), ESCA (normal =11, tumor =163), GBM (normal =5, tumor =169), HNSC (normal =44, tumor =504), KICH (normal =25, tumor =65), KIRC (normal =72, tumor =541), KIRP (normal =32, tumor =291), LAML (normal =0, tumor =150), LGG (normal =0, tumor =532), LIHC (normal =50, tumor =374), LUAD (normal =59, tumor =539), LUSC (normal =49, tumor =502), MESO (normal =0, tumor =87), OV (normal =0, tumor =381), PAAD (normal =4, tumor =179), PCPG (normal =3, tumor =184), PRAD (normal=52, tumor=501), READ (normal =10, tumor =167), SARC (normal =2, tumor =263), SKCM (normal =1, tumor =472), STAD (normal =32, tumor =375), TGCT (normal =0, tumor =156), THCA (normal =59, tumor =512), THYM (normal =2, tumor =120), UCEC (normal =35, tumor =554), UCS (normal =0, tumor =57), UVM (normal =0, tumor =80). (A) Except for ACC, DLBC, LAML, LGG, MESO, OV, SARC, SKCM, TGCT, THYM, UCS, and UVM, the P values of the other items from left to right were <0.001, 2.97e−27, 0.36, 2.82e−09, 3.09e−22, <0.001, 0.08, 5e−11, 0.69, 4.7e−11, 0.03, 1.76e−23, 7.88e−17, 5.87e−20, 0.54, 0.15, 0.17, 1.05e−06, 1.04e−16, 0.01, 0.17, respectively. (B) Except for SARC, SKCM, and THYM, the P values of the other items from left to right were 7.63e−06, 8.17e−11, >0.99, 0.008, 9.09e−13, 0.008, 2.59e−09, 0.89, 5.13e−10, <0.001, 2.58e−09, 2.27e−08, 1.27e−10, 0.62, 0.75, 0.01, 0.01, 4.92e−07, 0.01, and 0.16, respectively. ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large b-cell lymphoma; ESCA, esophageal squamous cell carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, brain lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; mRNA, messenger RNA; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SD, standard deviation; SKCM, skin cutaneous melanoma; STAD, stomach adenocarcinoma; TCGA, The Cancer Genome Atlas; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; TPM, transcripts per million; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.

Article Snippet: The representative immunohistochemistry (IHC) data of NAT10 are from the human protein atlas (HPA) ( https://www.proteinatlas.org/ ) (The patients id are 4012 and 2608, respectively).

Techniques: Expressing, Comparison, Standard Deviation

Journal: Translational Cancer Research

Article Title: Quetiapine inhibits the oxidative phosphorylation in head and neck squamous cell carcinoma through suppressing NAT10-mediated ac4C modification

doi: 10.21037/tcr-2025-1-2683

Figure Lengend Snippet: The relationship between NAT10 and the infiltration level of immune cells. *, P<0.05 by Pearson correlation analysis. The red box represent the correlation between NAT10 and immune cells in HNSCC. For HNSC, the P values from top to bottom were 0.549, <0.001, 3.86e−05, 9.81e−07, 1.99e−05, 0.37, 3.71e−06, 0.60, 0.002, 0.052, 0.31, 1.84e−05, 0.89, 2.82e−06, 2.11e−06, 0.03, 0.004, 0.26, 4.72e−05, 0.15, 0.11, 4.81e−08, 2.08e−09, and 0.04 , respectively. aDC, activated dendritic cell; DC, dendritic cell; HNSC, head and neck squamous cell carcinoma; iDC, immature dendritic cell; NK, natural killer; pDC, plasmacytoid dendritic cell; Tcm, central memory T cell; Tem, effector memory T cell; TFH, T follicular helper; Tgd, γδ T cell; Treg, regulatory T cell.

Article Snippet: The representative immunohistochemistry (IHC) data of NAT10 are from the human protein atlas (HPA) ( https://www.proteinatlas.org/ ) (The patients id are 4012 and 2608, respectively).

Techniques:

Journal: Translational Cancer Research

Article Title: Quetiapine inhibits the oxidative phosphorylation in head and neck squamous cell carcinoma through suppressing NAT10-mediated ac4C modification

doi: 10.21037/tcr-2025-1-2683

Figure Lengend Snippet: NAT10 was associated with poor prognosis in patients with HNSCC. (A) Representative images of IHC staining for NAT10 in tumor tissues compared to normal tissues ( http://www.rcsb.org/ , https://www.proteinatlas.org/ENSG00000135372-NAT10/tissue/oral+mucosa ; https://www.proteinatlas.org/ENSG00000135372-NAT10/cancer/head+and+neck+cancer ). (B) The relationship between NAT10 expression and T stage and grade; n=447 and n=483, respectively. P=0.02 (left) and P=0.01 (right). (C) ROC curves and AUC values; n=503. (D) Kaplan-Meier curve for cumulative survival time. HNSCC patients were separated by the median expression of NAT10; low =251, high =252. (E) Univariate and multivariate Cox regression analysis; n=503. *, P<0.05 by log-rank test. AUC, area under the curve; CI, confidence interval; FPR, false positive rate; G, grade; HNSCC, head and neck squamous cell carcinoma; HR, hazard ratio; IHC, immunohistochemistry; N, node; ROC, receiver operating characteristic; T, tumor; TPM, transcripts per million; TPR, true positive rate.

Article Snippet: The representative immunohistochemistry (IHC) data of NAT10 are from the human protein atlas (HPA) ( https://www.proteinatlas.org/ ) (The patients id are 4012 and 2608, respectively).

Techniques: Immunohistochemistry, Expressing

Journal: Translational Cancer Research

Article Title: Quetiapine inhibits the oxidative phosphorylation in head and neck squamous cell carcinoma through suppressing NAT10-mediated ac4C modification

doi: 10.21037/tcr-2025-1-2683

Figure Lengend Snippet: Enrichment analysis revealed that NAT10 could regulate the process of OXPHOS. (A) Volcano plot depicting DEGs. (B) GSEA enrichment map of DEGs. (C) GO enrichment map of DEGs. BP, biological process; CC, cellular component; CXCR, C-X-C chemokine receptor; DEG, differentially expressed gene; FDR, false discovery rate; GO, Gene Ontology; GSEA, gene set enrichment analysis; GTP, guanosine triphosphate; NES, normalized enrichment score; KEGG, Kyoto Encyclopedia of Genes and Genomes; MF, molecular function; OXPHOS, oxidative phosphorylation; sig, significance.

Article Snippet: The representative immunohistochemistry (IHC) data of NAT10 are from the human protein atlas (HPA) ( https://www.proteinatlas.org/ ) (The patients id are 4012 and 2608, respectively).

Techniques: Phospho-proteomics

Journal: Translational Cancer Research

Article Title: Quetiapine inhibits the oxidative phosphorylation in head and neck squamous cell carcinoma through suppressing NAT10-mediated ac4C modification

doi: 10.21037/tcr-2025-1-2683

Figure Lengend Snippet: Quetiapine could regulate NAT10-mediated ac4C modification in HNSCC. (A) The mainly potential drugs identified by L1000FWD database. (B) The chemical structure of quetiapine. (C) Molecular docking of NAT10 and quetiapine. (D) The binding sensorgram of the interactions between NAT10 and quetiapine. (E) The protein expression of NAT10 was detected through western blotting (left) and quantitatively analyzed (right); n=3. From left to right, P=0.001, <0.001, and 0.002, respectively. (F) The mRNA expression of NAT10 in HNSCC cells; n=3. From left to right, P=0.03, 0.002, and 0.08, respectively. (G) The protein expression of NAT10 after SCC-15 cells were treated with quetiapine was detected through western blotting (left) and quantitatively analyzed (right); n=3. P<0.001. (H) The mRNA expression of NAT10 after SCC-15 cells were treated with quetiapine; n=3. P<0.001. (I) Dot blot assay was conducted to assess the ac4C level. P<0.001. Data are presented as mean ± SD. ns, no significance; *, P<0.05; **, P<0.01; ***, P<0.001 by unpaired t -test. EGFR, epidermal growth factor receptor; HDAC, histone deacetylase; HNSCC, head and neck squamous cell carcinoma; MEK, methyl ethyl ketone; MOA, mechanism of action; mRNA, messenger RNA; NF-κB, nuclear factor kappa-B; PARP, poly ADP-ribose polymerase; PLK, polo-like kinase; RAF, Raf kinase; RU, response unit; SD, standard deviation.

Article Snippet: The representative immunohistochemistry (IHC) data of NAT10 are from the human protein atlas (HPA) ( https://www.proteinatlas.org/ ) (The patients id are 4012 and 2608, respectively).

Techniques: Modification, Binding Assay, Expressing, Western Blot, Dot Blot, Histone Deacetylase Assay, Standard Deviation