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

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

  • Nat Commun. 2021 Aug 16;12(1):4961. doi: 10.1038/s41467-021-25202-5.
Wei Liu  # 1 2 Lei Xie  # 1 Yao-Hui He  # 3 4 Zhi-Yong Wu  # 5 Lu-Xin Liu  # 1 Xue-Feng Bai 6 Dan-Xia Deng 1 Xiu-E Xu 1 Lian-Di Liao 1 Wan Lin 1 Jing-Hua Heng 1 Xin Xu 1 Liu Peng 1 Qing-Feng Huang 1 Cheng-Yu Li 1 Zhi-Da Zhang 1 Wei Wang 2 Guo-Rui Zhang 6 Xiang Gao 3 4 Shao-Hong Wang 5 Chun-Quan Li 6 Li-Yan Xu 7 Wen Liu 8 9 En-Min Li 10
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, the Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, China.
  • 2 College of Science, Heilongjiang Institute of Technology, Harbin, Heilongjiang, China.
  • 3 State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
  • 4 Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China.
  • 5 Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-Sen University, Shantou, Guangdong, China.
  • 6 School of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing, Heilongjiang, China.
  • 7 Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, the Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, China. [email protected]
  • 8 State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China. [email protected]
  • 9 Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian, China. [email protected]
  • 10 Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology, the Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, China. [email protected]
  • # Contributed equally.
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.

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