Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting

Wei Liu, Lei Xie, Yao-Hui He, Zhi-Yong Wu, Lu-Xin Liu, Xue-Feng Bai, Dan-Xia Deng, Xiu-E Xu, Lian-Di Liao, Wan Lin, Jing-Hua Heng, Xin Xu, Liu Peng, Qing-Feng Huang, Cheng-Yu Li, Zhi-Da Zhang, Wei Wang, Guo-Rui Zhang, Xiang Gao, Shao-Hong Wang, Chun-Quan Li, Li-Yan Xu (), Wen Liu () and En-Min Li ()
Additional contact information
Wei Liu: Shantou University Medical College
Lei Xie: Shantou University Medical College
Yao-Hui He: Xiamen University
Zhi-Yong Wu: Affiliated Shantou Hospital of Sun Yat-Sen University
Lu-Xin Liu: Shantou University Medical College
Xue-Feng Bai: Harbin Medical University
Dan-Xia Deng: Shantou University Medical College
Xiu-E Xu: Shantou University Medical College
Lian-Di Liao: Shantou University Medical College
Wan Lin: Shantou University Medical College
Jing-Hua Heng: Shantou University Medical College
Xin Xu: Shantou University Medical College
Liu Peng: Shantou University Medical College
Qing-Feng Huang: Shantou University Medical College
Cheng-Yu Li: Shantou University Medical College
Zhi-Da Zhang: Shantou University Medical College
Wei Wang: Heilongjiang Institute of Technology
Guo-Rui Zhang: Harbin Medical University
Xiang Gao: Xiamen University
Shao-Hong Wang: Affiliated Shantou Hospital of Sun Yat-Sen University
Chun-Quan Li: Harbin Medical University
Li-Yan Xu: Shantou University Medical College
Wen Liu: Xiamen University
En-Min Li: Shantou University Medical College

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Esophageal cancer (EC) is a type of aggressive cancer without clinically relevant molecular subtypes, hindering the development of effective strategies for treatment. To define molecular subtypes of EC, we perform mass spectrometry-based proteomic and phosphoproteomics profiling of EC tumors and adjacent non-tumor tissues, revealing a catalog of proteins and phosphosites that are dysregulated in ECs. The EC cohort is stratified into two molecular subtypes—S1 and S2—based on proteomic analysis, with the S2 subtype characterized by the upregulation of spliceosomal and ribosomal proteins, and being more aggressive. Moreover, we identify a subtype signature composed of ELOA and SCAF4, and construct a subtype diagnostic and prognostic model. Potential drugs are predicted for treating patients of S2 subtype, and three candidate drugs are validated to inhibit EC. Taken together, our proteomic analysis define molecular subtypes of EC, thus providing a potential therapeutic outlook for improving disease outcomes in patients with EC.

Date: 2021
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DOI: 10.1038/s41467-021-25202-5

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