The characteristics and clinical relevance of tumor fusion burden in head and neck squamous cell carcinoma

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 1; pp. 852 - 861
• Main Authors: He, Lirui, Ren, Dandan, Lv, Guoqing, Mao, Beibei, Wu, Lijia, Liu, Xiaoyu, Gong, Longlong, Liu, Ping
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.01.2023; John Wiley and Sons Inc; Wiley
• Subjects: Angiogenesis; Biomarkers, Tumor - genetics; Cancer; CD8 antigen; Chemokines; Clinical Relevance; Copy number; Cytolysis; Gene expression; Gene Expression Profiling; Gene fusion; Genomics; Head & neck cancer; Head and neck carcinoma; Head and Neck Neoplasms - genetics; head and neck squamous cell carcinoma; Heterozygosity; Histocompatibility antigen HLA; Human papillomavirus; Humans; immune infiltration; Immunotherapy; Infiltration; Loss of heterozygosity; Lymphocytes T; Male; Medical prognosis; Mesenchyme; Metastases; Metastasis; Microenvironments; Mutation; p53 Protein; Papillomavirus Infections - complications; Prognosis; Prostate cancer; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - genetics; Statistical analysis; Stem cells; tumor fusion burden; Tumor Microenvironment - genetics; Tumors; γ-Interferon; tumor fusion burden; immune infiltration; human papillomavirus; head and neck squamous cell carcinoma
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.4890

Background Recent studies suggest that tumor fusion burden (TFB) is a hallmark of immune infiltration in prostate cancer, the correlation of TFB with immune microenvironment, and genomic patterns in head and neck squamous cell carcinomas (HNSC) remain largely unclear. Methods Gene fusion, genomic, transcriptomic, and clinical data of HNSC patients from the cancer genome atlas (TCGA) database were collected to analyze the correlation of TFB with mutation patterns, tumor immune microenvironment, and survival time in HNSC patients. Results Human papillomavirus (HPV) (−) patients with low TFB exhibited significantly enhanced CD8+ T cells infiltration and cytolysis activity and increased level of interferon‐gamma (IL‐γ), human leukocyte antigen (HLA) class I, and chemokines. Moreover, TFB was positively correlated with TP53 mutation, score of gene copy number, and loss of heterozygosity (LOH), as well as the biological progress of epithelial‐mesenchymal transition (EMT), metastasis, and stem cell characteristics. Further analysis revealed that HPV (−) HNSC patients with low TFB have a better prognosis. Conclusions Our data revealed the correlation of TFB with tumor immune microenvironment and predictive features for immunotherapy, implying tumors with low TFB may be potential candidates for immunotherapeutic agents. Moreover, the TFB low group had prolonged overall survival (OS) in the HPV (−) HNSC cohort. In this study, we analyzed the TFB characteristics of HNSC in the TCGA database. Furthermore, we divided the HNSC patients into HPV negative and HPV positive groups, and investigated the gene mutation characteristics and immune cell distribution of the tumor microenvironment with regard to the TFB condition (high/low), as well as the impact on the survival of patients.