Proteomic Analysis of Human Esophageal Cancer Using Tandem Mass Tag Quantifications

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.

Advancements in Oncoproteomics Technologies: Treading toward Translation into Clinical Practice

“…TMTs, in addition to protein quantification, increase the detection sensitivity of certain highly hydrophilic analytes, such as phosphopeptides [ 207 , 208 ]. TMTs are widely applied in oncoproteomics analysis [ 205 , 209 , 210 , 211 , 212 , 213 ].…”

Naa10p promotes cell invasiveness of esophageal cancer by coordinating the c-Myc and PAI1 regulatory axis

“…Esophageal cancer (ESCA) is an aggressive malignancy with poor therapeutic outcomes [ 1 ]. Alterations in proteins and posttranslational modifications (PTMs) leading to the pathogenesis of ESCA have attracted much research attention [ 2 , 3 ]. Since large-scale genome profiling has identified several driver mutations and key regulation pathways but effective targeted therapy is still lacking, discovering novel pathological alterations in proteins may give rise to advances in drug development to fulfill the gap in current drug targets.…”

Proteomic analysis to identify markers for response to neoadjuvant treatment in esophageal and gastroesophageal cancer

“…As part of the effort to subcategorize gastroesophageal and identify biomarkers for response to treatment, previous esopahgeal cancer proteomics studies have identified markers for adverse outcome, such as GLUT1‐sialyl‐Tn antigen which is also expressed in other gastrointestinal cancers, 11 as well as differentially enriched proteins related to mitochondrial apoptosis, and regulation of angiogenesis. 12 However, most of these studies have compared esophageal cancer cells with healthy esophageal tissue cells. In the current study, we aimed to find proteomic biomarkers to predict a favorable response to neoadjuvant chemoradiation.…”