Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer
by
, , , ,
Smrita Singh
1,2,3
,
Mohd Younis Bhat
1,4, 
Gajanan Sathe
1,2,
Champaka Gopal
5,
Jyoti Sharma
1,
Anil K. Madugundu
1,2,6,
Neha S. Joshi
1,2,3 and
Akhilesh Pandey
1,3,6,* 1
Institute of Bioinformatics, International Technology Park, Bangalore 560066, India
2
Manipal Academy of Higher Education (MAHE), Manipal 576104, India
3
Center for Molecular Medicine, National Institute of Mental Health and Neuro-Sciences (NIMHANS), Bangalore 560029, India
4
Amrita School of Biotechnology, Amrita Vishwapeetham University, Kollam 690525, India
5
Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore 560029, India
6
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
Cancers 2021, 13(23), 5930; https://doi.org/10.3390/cancers13235930
Submission received: 28 October 2021
/
Revised: 20 November 2021
/
Accepted: 23 November 2021
/
Published: 25 November 2021
(This article belongs to the Special Issue Proteomics in Cancer)
Simple Summary
Gastric cancer comprises intestinal, diffuse and indeterminate subtypes based on histology. The intestinal and diffuse subtypes, although quite different in several respects, are still treated similarly. This study was designed to find differences at the protein level between the diffuse and intestinal subtypes using high-resolution mass spectrometry. We identified a differential proteomic signature of the two subtypes that included GREM1, BAG2, OLFM4, TRIP6 and MAGE-A9 proteins.
Abstract
Gastric cancer is a leading cause of death from cancer globally. Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry-based proteomics using tandem mass tags (TMT)-based multiplexed analysis was used to identify proteins in tumor tissues from patients with diffuse or intestinal gastric cancer with adjacent normal tissue control. A total of 7448 or 4846 proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two subtypes, which included gremlin1 (GREM1), bcl-2-associated athanogene 2 (BAG2), olfactomedin 4 (OLFM4), thyroid hormone receptor interacting protein 6 (TRIP6) and melanoma-associated antigen 9 (MAGE-A9) proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE-A9 have all been previously implicated in tumor progression and metastasis, they have not been linked to intestinal or diffuse subtypes of gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 124 cases of gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.
