Abstract

Esophageal cancer (EC) is a type of extremely aggressive gastrointestinal cancer with high incidences in China and other Asian countries. EC does not have specific symptoms and is relatively easy to metastasize, which makes it difficult in early diagnosis. Thus, novel noninvasive diagnostic method is urgently needed in clinical practice. In this study, mass spectrometry with tandem mass tags and differential protein analysis were applied for identifying esophageal cancer-related proteins. The identified proteins were annotated based on their enrichment in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In addition, hierarchical clustering was applied based on differentially expressed proteins. As a result, a total of 5131 quantifiable proteins were identified from our liquid chromatography-tandem mass spectrometry with tandem mass tags (LC-MS/MS-TMT) method with 63 upregulated and 97 downregulated differential proteins between esophageal cancer and controlled normal samples. The differentially expressed proteins were highly enriched in GO terms associated with mitochondrial dissemble and apoptosis, and blood vessel regulation, and the upregulated differentially expressed proteins in EC samples were significantly enriched in major histocompatibility complex MHC-class I/II pathway of immune system. The functional clustering analysis revealed potential protein-protein interactions among tetraspanin, myosin, and S-100. In summary, our study provided a practical technological procedure of proteomic analysis for discovering novel biomarkers of a specific cancer type.

Highlights

  • Esophageal cancer (EC) processes a significant health risk due to increasing incidence and poor prognosis [1]

  • As an extremely aggressive neoplasm, approximately 45,000 people are diagnosed with EC each year, while the overall 5-year survival rate is less than 10%

  • A total of 367174 secondary fingerprint spectra were obtained through mass spectrometry, and 98555 (26.8%) effective spectrograms obtained were filtered by MaxQuant. 47185 peptides were identified by spectrogram analysis with 96.9% unique peptides

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Summary

Introduction

Esophageal cancer (EC) processes a significant health risk due to increasing incidence and poor prognosis [1]. Chemotherapy and adjuvant chemotherapy are widely used in the treatment of esophageal cancer, the prognosis remains poor due to high possibility of tumor relapse or distant metastasis. Beginning in the mucosa of the esophagus and spreading through a deeper tissue layer, such as the submucosa, muscular layer, and serosa, esophageal cancer cells are able to metastatic progress through lymphatic and homogametic vessels. One hypothesis of the esophageal cancer model is the squamous epithelium undergoing chronic inflammatory changes, leading the changes in the cell structure and shape and in situ malignant changes as well [5,6,7]

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