Lee Young Chan, Nam Yonghyun, Kim Minjeong, Kim Su Il, Lee Jung-Woo, Eun Young-Gyu, Kim Dokyoon
Department of Otolaryngology-Head and Neck Surgery, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
Department of Medicine (AgeTech-Service Convergence Major) College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Aging (Albany NY). 2023 Dec 21;16(2):985-1001. doi: 10.18632/aging.205346.
The impact of the senescence related microenvironment on cancer prognosis and therapeutic response remains poorly understood. In this study, we investigated the prognostic significance of senescence related tumor microenvironment genes (PSTGs) and their potential implications for immunotherapy response. Using the Cancer Genome Atlas- head and neck squamous cell carcinoma (HNSC) data, we identified two subtypes based on the expression of PSTGs, acquired from tumor-associated senescence genes, tumor microenvironment (TME)-related genes, and immune-related genes, using consensus clustering. Using the LASSO, we constructed a risk model consisting of senescence related TME core genes (STCGs). The two subtypes exhibited significant differences in prognosis, genetic alterations, methylation patterns, and enriched pathways, and immune infiltration. Our risk model stratified patients into high-risk and low-risk groups and validated in independent cohorts. The high-risk group showed poorer prognosis and immune inactivation, suggesting reduced responsiveness to immunotherapy. Additionally, we observed a significant enrichment of STCGs in stromal cells using single-cell RNA transcriptome data. Our findings highlight the importance of the senescence related TME in HNSC prognosis and response to immunotherapy. This study contributes to a deeper understanding of the complex interplay between senescence and the TME, with potential implications for precision medicine and personalized treatment approaches in HNSC.
衰老相关微环境对癌症预后和治疗反应的影响仍知之甚少。在本研究中，我们调查了衰老相关肿瘤微环境基因（PSTGs）的预后意义及其对免疫治疗反应的潜在影响。利用癌症基因组图谱-头颈部鳞状细胞癌（HNSC）数据，我们通过一致性聚类，基于从肿瘤相关衰老基因、肿瘤微环境（TME）相关基因和免疫相关基因中获取的PSTGs表达，鉴定出两种亚型。利用套索回归，我们构建了一个由衰老相关TME核心基因（STCGs）组成的风险模型。这两种亚型在预后、基因改变、甲基化模式、富集通路和免疫浸润方面表现出显著差异。我们的风险模型将患者分为高风险和低风险组，并在独立队列中进行了验证。高风险组显示出较差的预后和免疫失活，提示对免疫治疗的反应性降低。此外，我们使用单细胞RNA转录组数据观察到STCGs在基质细胞中显著富集。我们的研究结果突出了衰老相关TME在HNSC预后和免疫治疗反应中的重要性。本研究有助于更深入地理解衰老与TME之间的复杂相互作用，对HNSC的精准医学和个性化治疗方法具有潜在意义。
