A TP53 mutation model for the prediction of prognosis and therapeutic responses in head and neck squamous cell carcinoma

Shi, Congyu; Liu, Shan; Tian, Xudong; Wang, Xiaoyi; Gao, Pan

doi:10.1186/s12885-021-08765-w

Cited by 20 publications

(13 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of TP53 mutation on OS prognosis was assessed according to Kaplan-Meier survival curve, TP53 mutation was a poor prognostic factor for OS. Our result was consistent with previous reports [13,14] . (Fig.…”

Section: Somatic Genomic Mutations In Hnsccsupporting

confidence: 94%

Predicting therapeutic responses in head and neck squamous cell carcinoma from TP53 mutation and The mutation of TP53 could be detected by cfDNA

Mei

Liu

Jiang

et al. 2023

Preprint

View full text Add to dashboard Cite

Objectives: Head and neck squamous cell carcinoma (HNSCC) was increasing globally. The mutation of the TP53 was the most common of all somatic genomic changes in HNSCC, and TP53 mutation was associated with the response of immunotherapeutic and chemotherapeutic. Tumor-derived circulating cell-free DNA (cfDNA) was minimally invasive method to determine genetic alterations for cancer. The study aimed to explore the therapeutic responses of TP53 mutation patients with HNSCC and the accuracy of cfDNA to detect TP53 mutation. Materials and methods: The information of TP53 mutations and patients’ survival time and clinical data in HNSCC was downloaded from The Cancer Genome Atlas (TCGA) Database. The difference of immune infiltration between TP53 mutant group and wild group was compared. The ssGSEA method applied to the transcriptome of HNSCC samples to assess the distribution of immune cell types between two groups. The chemotherapy response was constructed using the R software package, pRRophetic. GSEA enrichment analysis was performed based on TP53 mutation. The next-generation sequencing (NGS) was executed on cfDNA of 9 patients with HNSCC to detect genetic alterations. Tumor biopsy (n = 9) was sequenced using the same technique. Results: TP53 was the most frequently mutated gene in HNSCC. TP53 mutation was related to the immune cells and expression of immune-associated genes. The TP53 mutation group showed less response to immunotherapeutic but high sensitivity to some chemotherapies compared to wild-type group. TP53 was the most frequently mutated gene (6/9; 66.67%) in cfDNA. 27.27% of the tissue tumor variants were not detected in cfDNA when all TP53 mutations were considered. Conclusion: TP53 mutation could be used as a specific predictor of treatment response in patients with HNSCC. It was feasible to detect the TP53 mutations from HNSCC patients by cfDNA. The results suggested that the therapeutic response in patients could be predicted by detecting TP53 mutations in cfDNA, and large-scale and prospective studies were needed to validate it.

show abstract

Section: Somatic Genomic Mutations In Hnsccsupporting

confidence: 94%

Predicting therapeutic responses in head and neck squamous cell carcinoma from TP53 mutation and The mutation of TP53 could be detected by cfDNA

Mei

Liu

Jiang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…p53 is a tumor suppressor gene that frequently exhibits mutation in cancers [3]. Sixty-three percent of head and neck squamous cell carcinomas (HNSCC) contain p53 mutations, which is above the average of close to 50% for all types of cancer [4,5]. Previously, studies mostly focused on the loss of function (LoF) of the tumor suppressor role of wild-type p53, due to mutation, but, recently, there has been more focus on the gain of function (GoF) in mutant p53 proteins [5].…”

Section: Introductionmentioning

confidence: 99%

NAMPT Inhibitor and P73 Activator Represses P53 R175H Mutated HNSCC Cell Proliferation in a Synergistic Manner

et al. 2022

View full text Add to dashboard Cite

The p53 family has the following three members: p53, p63 and p73. p53 is a tumor suppressor gene that frequently exhibits mutation in head and neck cancer. Most p53 mutants are loss-of-function (LoF) mutants, but some acquire some oncogenic function, such as gain of function (GoF). It is known that the aggregation of mutant p53 can induce p53 GoF. The p73 activators RETRA and NSC59984 have an anti-cancer effect in p53 mutation cells, but we found that p73 activators were not effective in all head and neck squamous cell carcinoma (HNSCC) cell lines, with different p53 mutants. A comparison of the gene expression profiles of several regulator(s) in mutant HNSCC cells with or without aggregation of p53 revealed that nicotinamide phosphoribosyltransferase (NAMPT) is a key regulator of mutant p53 aggregation. An NAMPT inhibitor, to reduce abnormal aggregation of mutant p53, used in combination with a p73 activator, was able to effectively repress growth in HNSCC cells with p53 GoF mutants. This study, therefore, suggests a potential combination therapy approach for HNSCC with a p53 GoF mutation.

show abstract

“…48 Nevertheless, our research indicates that the existence of the magician in TP53 is connected with a poor outcome. 49,50 Immunotherapy for oncology has evolved rapidly over the last 20 years and has increased the treatment options for the various type of cancers. 51 Although most OV patients are not highly sensitive to immunotherapy, treatments with ICIs, TCR-engineered T cells and chimeric antigen receptors are evolving rapidly and providing new clinical thinking.…”

Section: Discussionmentioning

confidence: 99%

Ovarian carcinoma immune‐related microRNA affects the heterogeneity of the endocrine microenvironment and anti‐tumor immune pattern

Gao,

Wang,

Xiang

et al. 2023

The Journal of Gene Medicine

View full text Add to dashboard Cite

BackgroundThe eighth‐leading cause of cancer‐related mortality and the seventh‐most prevalent malignancy in women globally is ovarian cancer (OV). However, 5‐year survival expectancy after conventional treatment is not good. Therefore, there is an urgent need for novel signatures to guide the designation of therapeutic schemes for OV patients.MethodsWe used univariate Cox analysis to screen hormone secretion regulation axis‐related microRNAs (miRNAs), least absolute shrinkage and selection operator analysis to select candidate miRNAs and multivariate Cox analysis to build the risk model. To evaluate possible route and functional differences, enrichment analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on the differentially expressed genes (DEGs) across various risk groups. We compared Tumor Immune Dysfunction and Exclusion (TIDE) scores across risk categories by analyzing immune cell infiltration, immune checkpoint gene expression, immunological function and TIDE scores. In the end, we determined the half maximal inhibitory concentration (IC50) of chemotherapy and targeted medicines for individual patients. Cell assays were determined to test the migration of the miRNA‐target genes and western blotting was used to test the correlation of the miRNA‐target genes and the pathways.ResultsWe finally identified hormone secretion regulation axis‐related 13 microRNAs to build a risk model. The validation of observed and anticipated values revealed a fair level of agreement. To evaluate the molecular pathways between various groups in accordance with the GO and KEGG analyses, we then discovered 173 DEGs between distinct risk groups. The risk score was shown to be inversely related to the number of immune cells, including myeloid dendritic, granulocytes, M1 and M2 macrophages, B cells, t‐lymphocytes, and CD4+ and CD8+ cells, suggesting that immune cells are more frequent in the low‐risk group. Immune cell infiltration investigation yielded these results. Finally, we recognized 11 chemotherapeutic drugs and 30 novels targeted drugs on the basis of IC50 between the different risk groups. GJB5 was determined to be the mir‐219 target gene and was identified as promoting the cell cycle process. In addition, hormone secretion regulation axis related miRNAs were reported to affects the heterogeneity of endocrine microenvironment and anti‐tumor immune pattern.ConclusionsIn conclusion, a 13‐miRNA prognostic model was constructed to know the immune status, prognosis, immunotherapeutic response and anti‐tumor drug sensitivity for OV, which provides theoretical guidance for the effective and individualized treatment of OV patients.

show abstract

A TP53 mutation model for the prediction of prognosis and therapeutic responses in head and neck squamous cell carcinoma

Cited by 20 publications

References 62 publications

Predicting therapeutic responses in head and neck squamous cell carcinoma from TP53 mutation and The mutation of TP53 could be detected by cfDNA

Predicting therapeutic responses in head and neck squamous cell carcinoma from TP53 mutation and The mutation of TP53 could be detected by cfDNA

NAMPT Inhibitor and P73 Activator Represses P53 R175H Mutated HNSCC Cell Proliferation in a Synergistic Manner

Ovarian carcinoma immune‐related microRNA affects the heterogeneity of the endocrine microenvironment and anti‐tumor immune pattern

Contact Info

Product

Resources

About