Head and neck squamous cell carcinomas (HNSCCs) are a common type of cancer, ranking as the sixth most prevalent cancer worldwide and having a high morbidity and mortality rate. Among oropharyngeal squamous cell carcinoma (OPSCC) cancers, tonsillar squamous cell carcinoma (TSCC) is the most prevalent and has a particularly aggressive clinical course with poor disease outcomes. The tumor microenvironment (TME) of HNSCC is complex and heterogeneous, playing a crucial role in effective cancer therapy. Understanding the interaction between cancer inflammation, immunity, oncogenes, and tumor suppressor genes is essential for developing effective cancer treatments. This study aimed to gain a comprehensive understanding of the transcriptomes of the TME in TSCC, both associated with human papillomavirus (HPV) and not associated with HPV. The gene expression profiles of 168 genes linked to various cellular mediators and factors involved in inflammation, immunity crosstalk, transcription, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis were analyzed. We identified 40 differentially expressed genes related to the communication between tumor cells and the cellular mediators of inflammation and immunity crosstalk. In HPV-positive TSCC patients, 33 genes were over-expressed with a fold change greater than 1.5, and 26 of these genes were unique to this group. In contrast, HPV-negative TSCC patients had 11 up-regulated genes. The results further showed that 48 gene transcripts related to oncogenesis, tumor suppression, angiogenesis, and apoptosis were up-regulated in both HPV-positive and HPV-negative TSCC patients. Among the HPV-positive TSCC patients, 37 genes were over-expressed, while the HPV-negative TSCC patients had 11 up-regulated genes. The tumor microenvironment (TME) of HPV-associated and HPV-non-associated TSCC exhibited distinct characteristics, including the dysregulation of various genes involved in cellular mediators, inflammation, immunity crosstalk, transcription factors, immune signaling pathways, signal transduction, oncogenesis, tumor suppression, angiogenesis, and apoptosis. Additionally, we detected six Hr-HPV genotypes in 81% of the TSCC patients, with HPV-16 and HPV-35 being the most common types, followed by HPV-45 and HPV-18. HPV-39 and 31 were also identified. The presence of Hr-HPV genotypes in TSCC patients varied from single to multiple infections. In conclusion, we observed distinct heterogeneity in the transcriptome of the microenvironment in HPV-associated and non-associated TSCC. Further in vitro and in vivo studies are needed to investigate the functional implications of the identified over-expressed genes. Also, deeper molecular pathways and immunological studies on the TME are required to determine the potential of targeting genes for cancer therapy.
头颈部鳞状细胞癌（HNSCC）是一种常见的癌症类型，在全球范围内发病率位居第六，具有较高的发病率和死亡率。在口咽鳞状细胞癌（OPSCC）中，扁桃体鳞状细胞癌（TSCC）最为常见，其临床病程极具侵袭性，疾病预后较差。HNSCC的肿瘤微环境（TME）复杂且异质，在有效的癌症治疗中起着关键作用。理解癌症炎症、免疫、癌基因和抑癌基因之间的相互作用对于开发有效的癌症治疗方法至关重要。本研究旨在全面了解与人类乳头瘤病毒（HPV）相关及非相关的TSCC中TME的转录组特征。我们分析了168个基因的表达谱，这些基因涉及炎症、免疫交互、转录、信号转导、肿瘤发生、肿瘤抑制、血管生成和细胞凋亡等多种细胞介质和因子。我们鉴定出40个与肿瘤细胞和炎症及免疫交互的细胞介质之间通讯相关的差异表达基因。在HPV阳性TSCC患者中，33个基因表达上调，倍数变化大于1.5，其中26个基因为该组特有。相比之下，HPV阴性TSCC患者中有11个基因上调。结果进一步显示，在HPV阳性和HPV阴性TSCC患者中，与肿瘤发生、肿瘤抑制、血管生成和细胞凋亡相关的48个基因转录本均上调。在HPV阳性TSCC患者中，37个基因过表达，而HPV阴性TSCC患者中有11个基因上调。HPV相关和非HPV相关的TSCC的肿瘤微环境（TME）表现出不同的特征，包括参与细胞介质、炎症、免疫交互、转录因子、免疫信号通路、信号转导、肿瘤发生、肿瘤抑制、血管生成和细胞凋亡的多种基因失调。此外，我们在81%的TSCC患者中检测到六种高危型HPV基因型，其中HPV-16和HPV-35最为常见，其次是HPV-45和HPV-18，还鉴定出HPV-39和HPV-31。TSCC患者中高危型HPV基因型的存在从单一感染到多重感染不等。总之，我们观察到HPV相关和非相关TSCC微环境转录组存在明显的异质性。需要进行进一步的体外和体内研究，以探讨已鉴定的过表达基因的功能意义。同时，需要对TME进行更深入的分子通路和免疫学研究，以确定靶向基因在癌症治疗中的潜力。
肿瘤(癌症)患者之家