Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun;12(3):991-1006.
doi: 10.21037/jgo-21-278.

Identification of differentially expressed proteins in the locoregional recurrent esophageal squamous cell carcinoma by quantitative proteomics

Wei-Wei Yu  1 , Xiao-Long Fu  2 , Xu-Wei Cai  2 , Meng-Hong Sun  3 , Yan-Mei Guo  4
Affiliations

Identification of differentially expressed proteins in the locoregional recurrent esophageal squamous cell carcinoma by quantitative proteomics

Wei-Wei Yu et al. J Gastrointest Oncol. 2021 Jun.

Abstract

Background: This study aimed to identify potential biomarkers associated with locoregional recurrence in patients with esophageal squamous cell carcinoma (ESCC) after radical resection.

Methods: We performed a quantitative proteomics analysis using isobaric tags for relative and absolute quantification (iTRAQ) with reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) to identify differential expression proteins (DEPs) between a locoregional recurrence group and good prognosis group of ESCC after radical esophagectomy. The bioinformatics analysis was performed with ingenuity pathway analysis software (IPA) and Gene Ontology (GO) database using the software of MAS 3.0. Kaplan-Meier (KM) Plotter Online Tool (http://www.kmplot.com) was used to evaluate the relationship between the differential expression of proteins and survival in patients with ESCC.

Results: More than 400 proteins were quantitated of which 27 proteins had upregulated expression and 55 proteins had downregulated expression in the locoregional recurrence group compared to the good prognosis group. These 82 DEPs were associated with biological procession of cancer development including cellular movement, cellular assembly and organization, cellular function and maintenance, cellular growth and proliferation, cell death and survival, DNA replication recombination and repair, and so on. Of these DEPs, SPTAN1 and AGT proteins were identified to be associated with RFS in ESCC. SPTAN1 was positively associated with RFS and AGT was negatively associated with RFS. Expression of SPTAN1 tended to have favorable OS while expression of AGT tended to have poor OS.

Conclusions: Our results demonstrated that quantitative proteomics is an effective discovery tool to identify biomarkers for prognosis prediction in ESCC. However, it needs more studies with large populations of ESCC to validate these potential biomarkers.

Keywords: Biomarkers; esophageal carcinoma; quantitative proteomics; recurrence.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-278). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The work flow sheet. iTRAQ, Isobaric tags for relative and absolute quantification; SCX, strong cation exchange; RPLC-MS/MS: reversed phase liquid chromatography-tandem mass spectrometry.
Figure 2
Figure 2
Biofunctions and pathway analysis of the DEPs using IPA. (A) Biofunctions in which the DEPs are involved. (B) Canonical pathways that involved the DEPs. DEPs, differentially expressed proteins; IPA, ingenuity pathway analysis software.
Figure 3
Figure 3
The 3 significant pathway networks that involved the 82 DEPs. The red node represents up-regulated protein and the green node represents down-regulated protein. Uncolored nodes were not identified as DEPs, but were integrated into the computationally generated networks on the basis of the evidence stored in the IPA knowledge memory indicating a relevance to this network. DEPs, differentially expressed proteins; IPA, ingenuity pathway analysis software.
Figure 4
Figure 4
KM survival analysis for the relationship between survival and proteins expression of SPTAN1 and AGT in ESCC was performed using ESCC data of KM Plotter Online Tool. (A) Association of SPTAN1 with RFS in ESCC, (B) association of SPTAN1 with OS in ESCC, (C) association of AGT with RFS in ESCC, (D) association of AGT with OS in ESCC. KM, Kaplan-Meier; ESCC, esophageal squamous cell carcinoma; RFS, recurrence-free survival; OS, overall survival.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Nakajima M, Kato H. Treatment options for esophageal squamous cell carcinoma. Expert Opin Pharmacother 2013;14:1345-54. 10.1517/14656566.2013.801454 - DOI - PubMed
    1. Mariette C, Balon JM, Piessen G, et al. Pattern of recurrence following complete resection of esophageal carcinoma and factors predictive of recurrent disease. Cancer 2003;97:1616-23. 10.1002/cncr.11228 - DOI - PubMed
    1. Yamashita K, Watanabe M, Mine S, et al. Patterns and Outcomes of Recurrent Esophageal Cancer After Curative Esophagectomy. World J Surg 2017;41:2337-44. 10.1007/s00268-017-4024-5 - DOI - PubMed
    1. Macdonald JS, Smalley SR, Benedetti J, et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725-30. 10.1056/NEJMoa010187 - DOI - PubMed
    1. van Hagen P, Hulshof MC, van Lanschot JJ, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med 2012;366:2074-84. 10.1056/NEJMoa1112088 - DOI - PubMed