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Updated: Oct 23, 2025
Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal
Wei Liu1,2, Lei Xie1, Yao-Hui He3,4
1Guangdong 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.
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.
Insights
Researchers identified two molecular subtypes of esophageal cancer (EC) using proteomic analysis. The S2 subtype, marked by increased spliceosomal and ribosomal proteins, is more aggressive, offering new therapeutic targets for this cancer.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Esophageal cancer (EC) is an aggressive malignancy lacking clinically relevant molecular subtypes, which impedes effective treatment development.
- Current understanding of EC heterogeneity is limited, necessitating advanced molecular profiling to identify distinct subtypes.
Purpose of the Study:
- To define molecular subtypes of esophageal cancer through comprehensive proteomic and phosphoproteomic profiling.
- To identify diagnostic and prognostic markers and potential therapeutic targets for esophageal cancer subtypes.
Main Methods:
- Mass spectrometry-based proteomic and phosphoproteomics profiling was conducted on EC tumors and adjacent non-tumor tissues.
- Bioinformatic analysis was used to stratify the EC cohort into molecular subtypes based on proteomic data.
- Subtype-specific protein signatures and potential drug candidates were identified.
Main Results:
- Proteomic analysis stratified esophageal cancer into two molecular subtypes: S1 and S2.
- The S2 subtype exhibits upregulation of spliceosomal and ribosomal proteins and is associated with more aggressive disease.
- A subtype signature (ELOA and SCAF4) was identified, leading to a diagnostic and prognostic model.
- Three candidate drugs were validated for their efficacy in inhibiting EC growth in the S2 subtype.
Conclusions:
- Proteomic profiling successfully defined molecular subtypes of esophageal cancer, offering a new framework for understanding EC heterogeneity.
- The identification of the aggressive S2 subtype and its associated molecular signature provides potential therapeutic avenues.
- Validated candidate drugs offer a promising outlook for improving treatment strategies and patient outcomes in esophageal cancer.
