Dataset Information

Proteomic signatures of diffuse and intestinal subtypes of gastric cancer

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 7,804 or 5,166 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 132 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.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Gastric Epithelium, Gastric Mucosa

DISEASE(S): Diffuse Gastric Cancer,Stomach Carcinoma In Situ,Gastrointestinal Carcinoma

SUBMITTER: Akhilesh Pandey

LAB HEAD: Dr. Akhilesh Pandey

PROVIDER: PXD026279 | Pride | 2022-02-17

REPOSITORIES: Pride

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Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer.

Singh Smrita S Bhat Mohd Younis MY Sathe Gajanan G Gopal Champaka C Sharma Jyoti J Madugundu Anil K AK Joshi Neha S NS Pandey Akhilesh A

Cancers 20211125 23

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)-ba ...[more]

PMID: 34885041

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Project description:Gastric cancer ranks among the top ten most prevalent tumors worldwide, characterized by substantial heterogeneity and diverse morphological manifestations. Although postoperative histopathological examination serves as the cornerstone for determining Lauren classification, there exists a notable time lag in acquiring Lauren grade through this method. Furthermore, the invasiveness of detection techniques and limited tissue specimens markedly compromise the diagnostic precision of Lauren classification. Moreover, distinct molecular expression profiles exist between intestinal and diffuse types, yet the lack of molecular markers hampers the identification of these subtypes and their underlying mechanisms. Hence, our objective is to unearth biomarkers capable of distinguishing between intestinal and diffuse types and elucidate their mechanistic underpinnings, thereby refining the accuracy and applicability of Lauren classification. This pursuit holds promise for informing prognosis and optimizing treatment strategies for gastric cancer patients. Glycosylation emerges as a pivotal player in gastric cancer pathogenesis. Leveraging bioinformatics analyses on publicly available gastric cancer databases, we identified, at the transcriptomic level, elevated expression of the glycosylation-associated gene GXYLT2 in the diffuse subtype compared to the intestinal subtype. Subsequently, we corroborated these findings at both cellular and clinical tissue levels. Notably, GXYLT2 knockdown attenuated the proliferative, invasive, and sphere-forming capacities of gastric cancer cells in vitro. RNA-seq analysis and cellular validation unveiled that GXYLT2 depletion operates through inhibition of the Wnt/β-catenin signaling pathway. Encouragingly, in vivo validation demonstrated that GXYLT2 knockdown impedes gastric cancer growth. In conclusion, our study positions GXYLT2 as a potential biomarker capable of discerning between intestinal and diffuse subtypes, with prognostic implications in gastric cancer. Furthermore, we elucidate its role in gastric cancer progression via modulation of the Wnt/β-catenin signaling pathway.

			Action	DRS
	Diffuse_TP_1.raw	Raw
	Diffuse_TP_10.raw	Raw
	Diffuse_TP_11.raw	Raw
	Diffuse_TP_12.raw	Raw
	Diffuse_TP_12FR-_1_.pdResult	Other