NF-Y Subunits Overexpression in HNSCC

Bezzecchi, Eugenia; Bernardini, Andrea; Ronzio, Mirko; Miccolo, Claudia; Chiocca, Susanna; Dolfini, Diletta; Mantovani, Roberto

doi:10.3390/cancers13123019

Cited by 10 publications

(10 citation statements)

References 75 publications

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“…Bezzecchi et al. used TCGA RNA-seq to analyze the HPV+ and HPV- Neck squamous cell carcinoma (HNSC) revealing that the overexpression of histone fold domain subunits and NF-YAs is counteracting cancer progression in HPV+ patients ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Integration of scRNA-Seq and TCGA RNA-Seq to Analyze the Heterogeneity of HPV+ and HPV- Cervical Cancer Immune Cells and Establish Molecular Risk Models

et al. 2022

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BackgroundNumerous studies support that Human papillomavirus (HPV) can cause cervical cancer. However, few studies have surveyed the heterogeneity of HPV infected or uninfected (HPV+ and HPV-) cervical cancer (CESC) patients. Integration of scRNA-seq and TCGA data to analyze the heterogeneity of HPV+ and HPV- cervical cancer patients on a single-cell level could improve understanding of the cellular mechanisms during HPV-induced cervical cancer.MethodsCESC scRNA-seq data obtained from the Gene Expression Omnibus (GEO) database and the Seurat, Monocle3 package were used for scRNA-seq data analysis. The ESTIMATE package was used for single-sample gene immune score, CIBERSORT package was used to identify immune scores of cells, and the “WGCNA” package for the weighted correlation network analysis. Univariate Cox and LASSO regression were performed to establish survival and relapse signatures. KEGG and GO analyses were performed for the signature gene. Gene Expression Profiling Interactive Analysis was used for Pan-cancer analysis.ResultsIn the HPV+ CESC group, CD8+ T cells and B cells were down-regulated, whereas T reg cells, CD4+ T cells, and epithelial cells were up-regulated according to scRNA-seq data. Survival analysis of TCGA-CESC revealed that increased expression of naive B cells or CD8+ T cells favors the survival probability of CESC patients. WGCNA, univariate Cox, and LASSO Cox regression established a 9-genes survival signature and a 7-gene relapse model. Pan-cancer analysis identified IKZF3, FOXP3, and JAK3 had a similar distribution and effects in HPV-associated HNSC.ConclusionAnalysis of scRNA-seq and bulk RNA-seq of HPV+ and HPV- CESC samples revealed heterogeneity from transcriptional state to immune infiltration. Survival and relapse models were adjusted according to the heterogeneity of HPV+ and HPV- CESC immune cells to assess the prognostic risk accurately. Hub genes represent similar protection in HPV- associated HNSC while showing irrelevant to other potential HPV-related cancers.

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Section: Introductionmentioning

confidence: 99%

Integration of scRNA-Seq and TCGA RNA-Seq to Analyze the Heterogeneity of HPV+ and HPV- Cervical Cancer Immune Cells and Establish Molecular Risk Models

et al. 2022

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“…We stratified the progression free interval—PFI—of STAD patients according to High, Intermediate, Low levels of NF-Y subunits expression. In addition, we considered the ratios of NF-YAl/NF-YAs, because this parameter was more informative than the overall levels of the two isoforms to predict patient outcomes in breast, lung and HNSCC cancers 25 – 27 , 29 . No correlation is scored according to the different levels of NF-YA and of the HFD subunits (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Another study analyzing TCGA data found high expression of NF-YA, including of the protein in STAD specimens 31 ; this correlated with Cyclin E, a gene often amplified and overexpressed in STAD datasets 32 , 33 . These two studies did not report on the relative levels of the two major NF-YA subunits, which are clinically important in breast, lung and HNSCC cancers 25 – 27 , nor of the HFD subunits, which might be relevant in light on our recent finding on their overexpression in liver Hepatocarcinomas and HNSCC 28 , 29 . We report here on the analysis of STAD RNA-seq data present in TCGA, as further classified according to TCGA and ACRG.…”

Section: Introductionmentioning

confidence: 97%

“…Reports on the expression of NF-Y subunits in tumors emerged recently. In ovarian 22 , 23 , breast 24 , 25 , lung 26 , 27 , liver 28 and head and neck squamous cell carcinomas (HNSCC) 29 , overexpression of NF-YA was reported. As for gastric cancer, two studies provide evidence for a specific function of NF-YA: microarray-based differentially expressed genes (DEG) of gastric cancer identified NF-YA as a key TF, specifically in the DF subtype, with prognostic significance 30 ; NF-YA inactivation has a more profound growth suppressive effect in a DF than in a IT cell line.…”

Section: Introductionmentioning

confidence: 99%

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NF-Y subunits overexpression in gastric adenocarcinomas (STAD)

Gallo

Ronzio

Bezzecchi

et al. 2021

Sci Rep

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NF-Y is a pioneer transcription factor—TF—formed by the Histone-like NF-YB/NF-YC subunits and the regulatory NF-YA. It binds to the CCAAT box, an element enriched in promoters of genes overexpressed in many types of cancer. NF-YA is present in two major isoforms—NF-YAs and NF-YAl—due to alternative splicing, overexpressed in epithelial tumors. Here we analyzed NF-Y expression in stomach adenocarcinomas (STAD). We completed the partitioning of all TCGA tumor samples (450) according to molecular subtypes proposed by TCGA and ACRG, using the deep learning tool DeepCC. We analyzed differentially expressed genes—DEG—for enriched pathways and TFs binding sites in promoters. CCAAT is the predominant element only in the core group of genes upregulated in all subtypes, with cell-cycle gene signatures. NF-Y subunits are overexpressed, particularly NF-YA. NF-YAs is predominant in CIN, MSI and EBV TCGA subtypes, NF-YAl is higher in GS and in the ACRG EMT subtypes. Moreover, NF-YAlhigh tumors correlate with a discrete Claudinlow cohort. Elevated NF-YB levels are protective in MSS;TP53+ patients, whereas high NF-YAl/NF-YAs ratios correlate with worse prognosis. We conclude that NF-Y isoforms are associated to clinically relevant features of gastric cancer.

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“…Its location is 12q23.3. NFYB was highly expressed in multiple tumors and promotes tumor invasion, metastasis, and drug resistance [14][15][16]18]. However, the role of NFYB in gastric cancer has not been reported, so studying the effect of NFYB on GC may further clarify the possible mechanism of the occurrence and development of GC.…”

Section: Discussionmentioning

confidence: 99%

Over-expression of NFYB affects stromal cells reprogramming and predicts worse survival in gastric cancer patients

Xiang

et al. 2022

Aging

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Gastric cancer (GC) is the fifth most common cancer worldwide and the third most fatal. Cancer-associated fibroblasts (CAFs) play an essential role in promoting the occurrence and development of gastric cancer in all stages. NFYB is highly expressed in multiple tumors and promotes tumor invasion, metastasis, and drug resistance, but its role in the occurrence and development of gastric cancer remains unclear. Hence, we used TCGA, TIMER, Kaplan-Meier Plot, and UALCAN databases to analyze the expression of NFYB in pan-cancers and assess its clinical prognostic value. We found that high expression of NFYB may be a promising prognostic biomarker in patients with gastric cancer. High expression of NFYB was associated with high T stage, high histological grade, diffuse gastric cancer, and early-onset GC. Moreover, High expression of NFYB was associated with CAFs infiltration in the GC microenvironment. The prognosis of GC patients with high expression of NFYB and high infiltration of CAFs was worse. Therefore, NFYB may serve as a potential prognostic biomarker in patients with GC.

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NF-Y Subunits Overexpression in HNSCC

Cited by 10 publications

References 75 publications

Integration of scRNA-Seq and TCGA RNA-Seq to Analyze the Heterogeneity of HPV+ and HPV- Cervical Cancer Immune Cells and Establish Molecular Risk Models

Integration of scRNA-Seq and TCGA RNA-Seq to Analyze the Heterogeneity of HPV+ and HPV- Cervical Cancer Immune Cells and Establish Molecular Risk Models

NF-Y subunits overexpression in gastric adenocarcinomas (STAD)

Over-expression of NFYB affects stromal cells reprogramming and predicts worse survival in gastric cancer patients

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