Multi-omics insights into the molecular signature and prognosis of hypopharyngeal squamous cell carcinoma
Yanxin Ren, Wei Xiong, Chun Feng, Dan Yu, Xiaoyan Wang, Qin Yang, Siting Yu, Hongjiang Zhang, Bo Huo, Honglu Jiang, Zuli Li, Junlin Wang, Yu‐Xiong Su, Ping Yang, Yong Liao, Qi Zhong, Junwen Wang, Junwen Wang, Junwen Wang
Abstract
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. Males had higher prevalence and worse outcome in Chinese hypopharyngeal cancer patients. Estrogen response pathways are aberrantly regulated. Key CNVs include SOX2(3q26.33). Mutation of SYNE1 (HPV-) and MUC4 (HPV + ) were potential predictive markers.