Comprehensive analysis of radiosensitivity in head and neck squamous cell carcinoma

Li, Guangqi; Jiang, Yufei; Li, Guang; Qiao, Qiao

doi:10.1016/j.radonc.2021.03.017

Cited by 16 publications

(8 citation statements)

References 54 publications

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“…Many of these genes are directly associated with chemotherapy or radiotherapy resistance, in particular those that mediate DNA repair, including ATM , RB1 , and RAD21 , and acyl-CoA synthesis/ferroptosis, such as ACSL3 , ACSL4 , and FASN ( 49 – 55 ). Combination radiotherapy and immunotherapy have been proposed as a strategy to overcome single-therapy drug resistance, which aligns with our observation of elevated immune evasion genes in high-burden groups ( 56 ). Thus, patients with melanoma (TCGA) who exhibit a high burden of splicing neoantigens may have tumors that are resistant to chemotherapy and radiotherapy with up-regulated immune evasion capacity.…”

Section: Resultssupporting

confidence: 80%

Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy

Li,

Mahajan,

et al. 2024

Sci. Transl. Med.

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Immunotherapy has emerged as a crucial strategy to combat cancer by “reprogramming” a patient’s own immune system. Although immunotherapy is typically reserved for patients with a high mutational burden, neoantigens produced from posttranscriptional regulation may provide an untapped reservoir of common immunogenic targets for new targeted therapies. To comprehensively define tumor-specific and likely immunogenic neoantigens from patient RNA-Seq, we developed Splicing Neo Antigen Finder (SNAF), an easy-to-use and open-source computational workflow to predict splicing-derived immunogenic MHC-bound peptides (T cell antigen) and unannotated transmembrane proteins with altered extracellular epitopes (B cell antigen). This workflow uses a highly accurate deep learning strategy for immunogenicity prediction (DeepImmuno) in conjunction with new algorithms to rank the tumor specificity of neoantigens (BayesTS) and to predict regulators of mis-splicing (RNA-SPRINT). T cell antigens from SNAF were frequently evidenced as HLA-presented peptides from mass spectrometry (MS) and predict response to immunotherapy in melanoma. Splicing neoantigen burden was attributed to coordinated splicing factor dysregulation. Shared splicing neoantigens were found in up to 90% of patients with melanoma, correlated to overall survival in multiple cancer cohorts, induced T cell reactivity, and were characterized by distinct cells of origin and amino acid preferences. In addition to T cell neoantigens, our B cell focused pipeline (SNAF-B) identified a new class of tumor-specific extracellular neoepitopes, which we termed ExNeoEpitopes. ExNeoEpitope full-length mRNA predictions were tumor specific and were validated using long-read isoform sequencing and in vitro transmembrane localization assays. Therefore, our systematic identification of splicing neoantigens revealed potential shared targets for therapy in heterogeneous cancers.

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Section: Resultssupporting

confidence: 80%

Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy

Li,

Mahajan,

et al. 2024

Sci. Transl. Med.

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“…The emergence of tumour progression pathways among DEGs (n = 2781, Fig. 4 ) resembles transcriptomes of radioresistant HNSCCs, where hypoxia response, p53 pathway, NF-kB pathway and inflammatory response were found abnormally activated 30 .…”

Section: Discussionmentioning

confidence: 91%

Integrative analysis in head and neck cancer reveals distinct role of miRNome and methylome as tumour epigenetic drivers

Mandić,

Milutin Gašperov,

Božinović

et al. 2024

Sci Rep

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Head and neck cancer is the sixth most common malignancy worldwide, with the relatively low 5-year survival rate, mainly because it is diagnosed at a late stage. Infection with HPV is a well known aetiology, which affects the nature of these cancers and patients’ survival. Besides, it is considered that the main driving force for this type of cancer could be epigenetics. In this study we aimed to find potential epigenetic biomarkers, by integrating miRNome, methylome, and transcriptome analyses. From the fresh head and neck cancer tissue samples, we chose a group for miRNome, methylome and transcriptome profiling, in comparison to adequate control samples. Bioinformatics analyses are performed in R v4.2.2. Count normalisation and group differential expression for mRNA and the previously obtained miRNA count data was performed with DESeq2 v1.36. Gene set enrichment analysis was performed and visualised using gProfiler2 v0.2.1 Identification of miRNA targets was performed by querying in miRTarBase using multiMiR v1.18.0. Annotation of CpG sites merging into islands was obtained from RnBeads.hg19 v1.28.0. package. For the integrative analysis we performed kmeans clustering using stats v4.2.2 package, using 8–12 clusters and nstart 100. We found that transcriptome analysis divides samples into cancers and controls clusters, with no relation to HPV status or cancer anatomical location. Differentially expressed genes (n = 2781) were predominantly associated with signalling pathways of tumour progression. We identified a cluster of genes under the control of the transcription factor E2F that are significantly underexpressed in cancer tissue, as well as T cell immunity genes and genes related to regulation of transcription. Among overexpressed genes in tumours we found those that belong to cell cycle regulation and vasculature. A small number of genes were found significantly differentially expressed in HPV-positive versus HPV-negative tumours (for example NEFH, ZFR2, TAF7L, ZNF541, and TYMS). In this comprehensive study on an overlapping set of samples where the integration of miRNome, methylome and transcriptome analysis were performed for head and neck cancer, we demonstrated that the majority of genes were associated exclusively with miRNome or methylome and, to a lesser extent, under the control of both epigenetic mechanisms.

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“…Among factors limiting HNSCC radiosensitivity, recent evidence points to expression of immune checkpoint proteins, limited antigen presentation and T cell dysfunction [146],…”

Section: Radiation Sensitizationmentioning

confidence: 99%

Statins in Cancer Prevention and Therapy

Ricco

Kron

2023

Cancers

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Statins, a class of HMG-CoA reductase inhibitors best known for their cholesterol-reducing and cardiovascular protective activity, have also demonstrated promise in cancer prevention and treatment. This review focuses on their potential applications in head and neck cancer (HNC), a common malignancy for which established treatment often fails despite incurring debilitating adverse effects. Preclinical and clinical studies have suggested that statins may enhance HNC sensitivity to radiation and other conventional therapies while protecting normal tissue, but the underlying mechanisms remain poorly defined, likely involving both cholesterol-dependent and -independent effects on diverse cancer-related pathways. This review brings together recent discoveries concerning the anticancer activity of statins relevant to HNC, highlighting their anti-inflammatory activity and impacts on DNA-damage response. We also explore molecular targets and mechanisms and discuss the potential to integrate statins into conventional HNC treatment regimens to improve patient outcomes.

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Comprehensive analysis of radiosensitivity in head and neck squamous cell carcinoma

Cited by 16 publications

References 54 publications

Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy

Splicing neoantigen discovery with SNAF reveals shared targets for cancer immunotherapy

Integrative analysis in head and neck cancer reveals distinct role of miRNome and methylome as tumour epigenetic drivers

Statins in Cancer Prevention and Therapy

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