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Quantitative tissue proteome profile reveals neutrophil degranulation and remodeling of extracellular matrix proteins in early stage gallbladder cancer

Authors :
Javed Akhtar
Vaishali Jain
Radhika Kansal
Ratna Priya
Puja Sakhuja
Surbhi Goyal
Anil Kumar Agarwal
Vivek Ghose
Ravindra Varma Polisetty
Ravi Sirdeshmukh
Sudeshna Kar
Poonam Gautam
Source :
Frontiers in Oncology. 12
Publication Year :
2023
Publisher :
Frontiers Media SA, 2023.

Abstract

Gallbladder cancer (GBC) is an aggressive malignancy of the gastrointestinal tract with a poor prognosis. It is important to understand the molecular processes associated with the pathogenesis of early stage GBC and identify proteins useful for diagnostic and therapeutic strategies. Here, we have carried out an iTRAQ-based quantitative proteomic analysis of tumor tissues from early stage GBC cases (stage I, n=7 and stage II, n=5) and non-tumor controls (n=6) from gallstone disease (GSD). We identified 357 differentially expressed proteins (DEPs) based on ≥ 2 unique peptides and ≥ 2 fold change with p value < 0.05. Pathway analysis using the STRING database showed, ‘neutrophil degranulation’ to be the major upregulated pathway that includes proteins such as MPO, PRTN3, S100A8, MMP9, DEFA1, AZU, and ‘ECM organization’ to be the major downregulated pathway that includes proteins such as COL14A1, COL1A2, COL6A1, COL6A2, COL6A3, BGN, DCN. Western blot and/or IHC analysis confirmed the elevated expression of MPO, PRTN3 and S100A8 in early stage of the disease. Based on the above results, we hypothesize that there is an increased neutrophil infiltration in tumor tissue and neutrophil degranulation leading to degradation of extracellular matrix (ECM) proteins promoting cancer cell invasion in the early stage GBC. Some of the proteins (MPO, MMP9, DEFA1) associated with ‘neutrophil degranulation’ showed the presence of ‘signal sequence’ suggesting their potential as circulatory markers for early detection of GBC. Overall, the study presents a protein dataset associated with early stage GBC.

Subjects

Subjects :
Cancer Research
Oncology

Details

Language :
English
ISSN :
2234943X
Volume :
12
Database :
OpenAIRE
Journal :
Frontiers in Oncology
Accession number :
edsair.doi.dedup.....0c42a555149274b3fb849b7abd8ac33b
Full Text :
https://doi.org/10.3389/fonc.2022.1046974