TP53 mutation-associated immune infiltration and a novel risk score model in HNSCC

Kong, Weili; Han, Yinze; Gu, Hailing; Yang, Hui; Zang, Yi

doi:10.1016/j.bbrep.2022.101359

Cited by 3 publications

(2 citation statements)

References 37 publications

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“…Of these, tumor protein P53 (TP53) had the highest mutation rate at 66%. This indicated that mutations in TP53 were closely related to the development of HNSCC tumors, and tumors might be caused by changes in the immune microenvironment of mutant TP53 ( 13 ).…”

Section: Resultsmentioning

confidence: 98%

Construction of a prognosis model of head and neck squamous cell carcinoma pyroptosis and an analysis of immuno-phenotyping based on bioinformatics

Pan,

Huang,

Zheng

et al. 2024

Transl Cancer Res

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Background Head and neck squamous cell carcinoma (HNSCC) is currently the sixth most common cancer worldwide, and its prevalence and recurrence rates are gradually increasing. To study the relationship between HNSCC and cell pyroptosis and provide new treatment options for HNSCC, a prognostic model of pyroptosis-related genes (PRGs) was established to predict the prognosis of patients with HNSCC, and an immune correlation analysis was performed. Methods A total of 53 PRGs were selected. We comprehensively analyzed the role of these PRGs in HNSCC through multiple omics data-set integration. We then identified two different molecular subtypes and found that changes in multi-layer PRGs were associated with clinicopathological characteristics, prognosis, and tumor microenvironment cell-infiltration characteristics in patients. Next, prognostic models were generated for nine PRGs; that is, cytotoxic T lymphocyte antigen 4 ( CTLA4 ), V-set and immunoglobulin domain containing 4 ( VSIG4 ), heparin-binding-epidermal growth factor ( HBEGF ), aquaporin-1 ( AQP1 ), s odium channel epithelial 1 subunit delta ( SCNN1D ), argininosuccinate synthase 1 ( ASS1 ), f amily with sequence similarity 83 member ( FAM83 ), c yclin dependent kinase inhibitor 2A ( CDKN2A ), and s erine protease inhibitor Kazal 6 ( SPINK6 ). Finally, a risk-score model was constructed, and the Kaplan-Meier method was used to evaluate overall survival. In addition, the immune environment and drug sensitivity were analyzed. Results This study showed that pyroptosis is closely related to HNSCC. The scores generated by the risk markers based on the new nine PRGs were identified as independent risk factors for predicting HNSCC. The differentially expressed genes between the low- and high-risk groups were further found to be related to the tumor immune cells and pathways. In addition, the risk score was found to be significantly correlated with chemosensitivity. Conclusions Our comprehensive analysis of PRGs revealed their potential role in the tumor immune microenvironment, clinicopathological characteristics, and prognosis. These findings may improve our understanding of pyroptosis in HNSCC and may provide new ideas for evaluating prognosis and developing more effective immunotherapy strategies.

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Section: Resultsmentioning

confidence: 98%

Construction of a prognosis model of head and neck squamous cell carcinoma pyroptosis and an analysis of immuno-phenotyping based on bioinformatics

Pan,

Huang,

Zheng

et al. 2024

Transl Cancer Res

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“…This suggests that signature genes related to PLK4 could serve as predictive biomarkers for the development of therapeutic agents targeting PLK4. Building on previous investigations that have highlighted the correlation between TP53 mutations and the tumor immune microenvironment [ 36 , 37 , 38 ], an in-depth exploration of the interplay between PLK4 and immunity is imperative. Using a cellular assay and syngeneic and NOD/SCID mouse model, a previous study showed that the mutant p53 protein blocks the formation of the STING-TBK1-IRF3 trimeric complex that inactivates innate immune signals, leading to immune evasion [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Polo-like Kinase 4: A Multifaceted Marker Linking Tumor Aggressiveness and Unfavorable Prognosis, and Insights into Therapeutic Strategies

Kim,

Hwang,

Kim

et al. 2023

Cancers

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(1) Background: This study investigated whether polo-like kinase 4 (PLK4) is a suitable therapeutic target or biomarker for lung adenocarcinoma (LUAD). (2) Methods: We acquired LUAD data from The Cancer Genome Atlas (TCGA) database through the UCSC Xena data portal. Gene expression, clinical, survival, and mutation data from multiple samples were analyzed. Gene enrichment analysis, unsupervised clustering of PLK4-related pathways, and differential gene expression analyses were performed. Additionally, correlations, t-tests, survival analyses, and statistical analyses were performed. (3) Results: PLK4 expression was higher in LUAD tissues than in normal tissues and was associated with poor prognosis for both overall and progression-free survival in LUAD. PLK4 was highly correlated with cell-proliferation-related pathways using Gene Ontology (GO) biological process terms. PLK4 expression and pathways that were highly correlated with PLK4 expression levels were upregulated in patients with LUAD with the TP53 mutation. (4) Conclusions: PLK4 expression affects the survival of patients with LUAD and is a potential therapeutic target for LUAD with TP53 mutations.

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Construction of lysosome‐related prognostic signature to predict the survival outcomes and selecting suitable drugs for patients with HNSCC

Cao,

Gu,

Shen

et al. 2024

BioFactors

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Lysosomes are digestive organelles responsible for endocytosis and autophagy. Recently, the malignancy and invasiveness head and neck squamous cell carcinoma (HNSCC) has been increasingly studied with the role of lysosomes. A list of lysosome‐related genes were obtained from MSigDB. A Spearman correlation and univariate Cox regression analyses combined with differential expression analysis were conducted to detect differentially expressed lysosome‐related genes related to prognosis. The prediction of prognostic signature was evaluated by plotting survival curve, ROC, and by developing a nomogram. Immune subtypes, infiltration of immune cells, GSVA, TIDE, IC50 of common chemotherapy and targeted therapy, GO, and KEGG function enrichment analyses were carried out to explore the immune microenvironment of the signature. We constructed a lysosome‐related prognostic signature that could function as an independent prognostic indicator for patients with HNSCC. High‐risk patients were better suited to receive Doxorubicin, Mitomycin C, Pyrimethamine, anti‐PD‐L1 and anti‐CTLA‐4 immunotherapy, whereas low‐risk patients had sensitivity to Lapatinib. GO functional enrichment analysis showed that prognostic features were strongly associated with epidermis‐related functions (e.g., epidermal cell differentiation, epidermal development, and keratinization). In addition, a KEGG function enrichment analysis revealed a potential relationship between the risk assessment model and cardiomyopathy. We constructed a prognostic signature based on lysosome‐related genes and successfully predicted the survival outcome of HNSCC patients, which not only provides potential guidance for personalized treatment but also provides a new idea for precision treatment of HNSCC.

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TP53 mutation-associated immune infiltration and a novel risk score model in HNSCC

Cited by 3 publications

References 37 publications

Construction of a prognosis model of head and neck squamous cell carcinoma pyroptosis and an analysis of immuno-phenotyping based on bioinformatics

Construction of a prognosis model of head and neck squamous cell carcinoma pyroptosis and an analysis of immuno-phenotyping based on bioinformatics

Polo-like Kinase 4: A Multifaceted Marker Linking Tumor Aggressiveness and Unfavorable Prognosis, and Insights into Therapeutic Strategies

Construction of lysosome‐related prognostic signature to predict the survival outcomes and selecting suitable drugs for patients with HNSCC

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