头颈部鳞状细胞癌(HNSCC)是一种常见的癌症,位居全球第六,发病率和死亡率高。在口咽鳞状细胞癌(OPSCC)癌症中,扁桃体鳞状细胞癌(TSCC)是最普遍的,具有特别积极的临床病程,疾病预后较差。HNSCC的肿瘤微环境(TME)是复杂和异质的,在有效的癌症治疗中起着至关重要的作用。了解癌症炎症之间的相互作用,豁免权,致癌基因,而肿瘤抑制基因对于开发有效的癌症治疗至关重要。本研究旨在全面了解TSCC中TME的转录组,既与人乳头瘤病毒(HPV)相关,也与HPV无关。与各种细胞介质和参与炎症的因子相关的168个基因的基因表达谱,抗扰性串扰,转录,信号转导,肿瘤发生,肿瘤抑制,血管生成,和细胞凋亡进行分析。我们鉴定了40个与肿瘤细胞与炎症和免疫串扰的细胞介质之间的通讯有关的差异表达基因。在HPV阳性的TSCC患者中,33个基因以大于1.5的倍数变化过表达,其中26个基因是该组独有的。相比之下,HPV阴性的TSCC患者有11个上调的基因。结果进一步表明,48个基因转录本与肿瘤发生、肿瘤抑制,血管生成,在HPV阳性和HPV阴性的TSCC患者中细胞凋亡均上调。在HPV阳性的TSCC患者中,37个基因过表达,而HPV阴性的TSCC患者有11个基因上调。HPV相关和HPV非相关TSCC的肿瘤微环境(TME)表现出不同的特征,包括参与细胞介质的各种基因的失调,炎症,抗扰性串扰,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,和凋亡。此外,我们在81%的TSCC患者中检测到六种Hr-HPV基因型,HPV-16和HPV-35是最常见的类型,其次是HPV-45和HPV-18。还鉴定了HPV-39和31。TSCC患者中Hr-HPV基因型的存在从单次感染到多次感染不等。总之,我们观察到HPV相关和非相关TSCC微环境转录组的明显异质性.需要进一步的体外和体内研究来研究鉴定的过表达基因的功能意义。此外,需要对TME进行更深入的分子途径和免疫学研究,以确定靶向基因用于癌症治疗的潜力。
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.