Ren Yanxin, Xiong Wei, Feng Chun, Yu Dan, Wang Xiaoyan, Yang Qing, Yu Siting, Zhang Hongjiang, Huo Bangyun, Jiang Honglu, Li Zuli, Wang Junlin, Su Yu-Xiong, Yang Ping, Liao Yong, Zhong Qi, Wang Junwen
Department of Head and Neck Surgery, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
Department of Radiotherapy, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, China.
Commun Biol. 2025 Mar 5;8(1):370. doi: 10.1038/s42003-025-07700-0.
Approximately two-thirds of hypopharyngeal squamous cell carcinoma (HPSCC) cases are diagnosed at advanced stages, with the worst prognosis among head and neck squamous cell carcinomas (HNSCCs). Identifying biomarkers for high-risk patients requiring aggressive treatment is crucial. We present mutational, transcriptomic, and proteomic studies of 103 Chinese HPSCC patients and observe a higher prevalence and poorer prognosis in males. Estrogen response pathways are up-regulated, and proteins phosphorylated by protein kinase C (PKC) and cyclin-dependent kinases (CDKs) are aberrantly regulated in HPSCC. We identify aberrant copy number regions including SOX2(3q26.33), FGFR(8p11.23), CCND1(11q13.3), CDKN2A/2B(9p21.3), and MYC(8q24.21). Human papillomavirus (HPV) status combined with highly mutated genes, such as SYNE1 in HPV(-) and MUC4 in HPV(+) patients, were assessed as prognosis markers. A predictive model involving clinical factors and expression of six genes was established and cross-site validated. These findings open new opportunities for stratifying high-risk patients and molecular targets for personalized therapeutic strategies.
大约三分之二的下咽鳞状细胞癌（HPSCC）病例在晚期被诊断出来，其预后在头颈部鳞状细胞癌（HNSCC）中最差。识别需要积极治疗的高危患者的生物标志物至关重要。我们对103例中国HPSCC患者进行了突变、转录组和蛋白质组学研究，观察到男性患病率更高且预后更差。雌激素反应途径上调，蛋白激酶C（PKC）和细胞周期蛋白依赖性激酶（CDK）磷酸化的蛋白质在HPSCC中异常调节。我们确定了异常拷贝数区域，包括SOX2（3q26.33）、FGFR（8p11.23）、CCND1（11q13.3）、CDKN2A/2B（9p21.3）和MYC（8q24.21）。评估了人乳头瘤病毒（HPV）状态与高突变基因的组合，如HPV（-）患者中的SYNE1和HPV（+）患者中的MUC4，作为预后标志物。建立了一个涉及临床因素和六个基因表达的预测模型并进行了跨位点验证。这些发现为分层高危患者提供了新的机会，并为个性化治疗策略提供了分子靶点。
