Kim Min Ji, Hong Jisu, Chang Hyo Won, Lee Yun-Hee, Myong Jun-Pyo, Jung Ah Ra, Lee Yoon Se, Kwon Minsu
Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Transl Oncol. 2025 Feb;52:102229. doi: 10.1016/j.tranon.2024.102229. Epub 2024 Dec 4.
Laryngeal cancer (LC) presents a significant health challenge globally, with smoking being a major risk factor. Interestingly, LC incidence in females is significantly lower than in males; however, female smokers are more likely to develop Reinke edema (RE) than LC. This study sought to investigate whether autophagy, a major mechanism for RE development, acts as a defense mechanism in laryngeal tissue against cigarette exposure and suppresses LC development in females who smoke.
This study analyzed the National Health Insurance Service (NHIS) data of South Korea to explore sex differences in LC incidence and clinical outcomes. Protein expression was compared between tissues from LC and RE patients. The changes in autophagy-related markers were analyzed after exposure to human vocal fold fibroblast (hVFF) and cigarette smoke extract (CSE). In addition, to explore the relationship between the level of autophagy-related gene expression and clinical features, female LC patients were compared with male patients through an analysis of data from The Cancer Genome Atlas (TCGA).
In the NHIS data analyses, male LC patients had an 11 times higher incidence than female patients, even after adjusting for smoking and age. Additionally, female LC patients had significantly better survival rates. RE tissues exhibited increased autophagy-related protein expression compared with LC tissues. hVFFs after CSE exposure demonstrated elevated autophagy markers along with protein expression similar to RE tissue, suggesting autophagy's role in RE development over LC. The TCGA data analysis did not find a significant difference in autophagy-related gene expression, which would explain the favorable female clinical outcomes, between male and female LC patients.
This study implies autophagy activation by cigarette smoke is a crucial mechanism for lower LC incidence and better outcomes in females, highlighting the potential for autophagy-targeted LC prevention and treatment strategies.
喉癌（LC）在全球范围内对健康构成重大挑战，吸烟是主要风险因素。有趣的是，女性喉癌发病率显著低于男性；然而，女性吸烟者比患喉癌更易发生任克氏水肿（RE）。本研究旨在调查自噬这一RE发生的主要机制，是否在喉组织中作为一种防御机制抵御香烟暴露，并抑制吸烟女性的喉癌发生。
本研究分析了韩国国民健康保险服务（NHIS）的数据，以探讨喉癌发病率和临床结果的性别差异。比较了喉癌和RE患者组织中的蛋白质表达。在人声带成纤维细胞（hVFF）暴露于香烟烟雾提取物（CSE）后，分析自噬相关标志物的变化。此外，为了探究自噬相关基因表达水平与临床特征之间的关系，通过分析癌症基因组图谱（TCGA）的数据，将女性喉癌患者与男性患者进行比较。
在NHIS数据分析中，即使在调整吸烟和年龄因素后，男性喉癌患者的发病率仍比女性患者高11倍。此外，女性喉癌患者的生存率显著更高。与喉癌组织相比，RE组织中自噬相关蛋白表达增加。CSE暴露后的hVFF显示出自噬标志物升高以及与RE组织相似的蛋白质表达，表明自噬在RE发生而非喉癌发生中起作用。TCGA数据分析未发现自噬相关基因表达在男性和女性喉癌患者之间存在显著差异，而这一差异本可解释女性较好的临床结果。
本研究表明香烟烟雾激活自噬是女性喉癌发病率较低和预后较好的关键机制，突出了以自噬为靶点的喉癌预防和治疗策略的潜力。
