Large-scale and high-resolution mass spectrometry-based proteomics defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting PMID: 42331772

ADC Targets in Oncology

2026-04-10

Large-scale and high-resolution mass spectrometry-based proteomics defines molecular subtypes of nasopharyngeal carcinoma for therapeutic targeting

Signal Transduct Target Ther. 2026 Jun 23;11(1):244. doi: 10.1038/s41392-026-02742-0.

Yi-Ping Wu ^# ¹ ² , Yao-Hui He ^# ³ ⁴ ⁵ , Guo-Sheng Hu ^# ³ ⁴ ⁶ , Zhi-Qin Li ^# ² , Qing-Wen Li ¹ ² , Xiao-Tong Chen ¹ ² , Hui-Ying Ling ¹ ² , Wen Liu ⁷ ⁸ ⁹ ¹⁰ ¹¹ , Qin Lin ¹² ¹³

Affiliations

1. Department of Radiation Oncology, Xiamen Key Laboratory of Radiation Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
2. Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China.
3. State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, Fujian, China.
4. Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, Fujian, China.
5. Institute for Future Sciences, University of South China, Changsha, Hunan, China.
6. Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou, China.
7. Department of Radiation Oncology, Xiamen Key Laboratory of Radiation Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China. [email protected].
8. Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China. [email protected].
9. State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, Fujian, China. [email protected].
10. Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiang'an South Road, Xiamen, Fujian, China. [email protected].
11. Shenzhen Research Institute of Xiamen University, Shenzhen, Guangdong, China. [email protected].
12. Department of Radiation Oncology, Xiamen Key Laboratory of Radiation Oncology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China. [email protected].
13. Xiamen Cancer Center, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China. [email protected].
# Contributed equally.

Abstract

Challenges in the precise diagnosis and treatment of nasopharyngeal carcinoma (NPC) remain, mainly due to the absence of a multi-omics-based molecular classification and effective targeted therapies. In this study, we performed proteomic and phosphoproteomic analyses of NPC and non-cancerous nasopharyngeal tissues to identify key dysregulated proteins and phosphorylation networks. Based on these profiles, we classified NPC into two distinct molecular subtypes: S1 and S2, which exhibit significant clinical heterogeneity. Notably, the S2 subtype displayed stronger immune suppressive characteristics. By leveraging proteomic data from both cancerous and non-cancerous tissues, as well as from the two molecular subtypes, we developed robust diagnostic and prognostic models. Through computational drug repurposing and experimental validation, we identified Panobinostat, a pan-histone deacetylase inhibitor, as a potent anti-tumor agent for NPC, demonstrating efficacy in both in vitro and in vivo models. Mechanistically, Panobinostat inhibits MYC expression, thereby suppressing the transcriptional activation of key components in the homologous recombination (HR) DNA repair pathway. This reduction in transcriptional activation impairs HR repair efficiency and leads to the accumulation of DNA double-strand breaks (DSBs). Furthermore, combination therapy with Panobinostat and radiotherapy produced a synergistic effect, significantly enhancing NPC suppression. Additionally, we predicted and validated potential drugs for targeting the S2 subtype of NPC. In conclusion, we identified molecular subtypes of NPC, constructed preliminary diagnostic and prognostic marker panels, and observed the therapeutic potential of Panobinostat, as a monotherapy and in combination with radiotherapy. These findings provide a solid foundation for precision diagnosis, prognostic stratification, and personalized treatment strategies for NPC.