Mapping of DOG1 expression in colorectal carcinomas

Area of Science:

• Oncology
• Molecular Biology
• Gastroenterology

Background:

• Discovery on Gastrointestinal stromal tumour 1 (DOG1) is a calcium-activated chloride channel involved in cell signaling.
• DOG1 is expressed in various cell types, including those in the gastrointestinal tract.
• Its role in colorectal carcinoma (CRC) pathogenesis and prognosis is not fully understood.

Purpose of the Study:

• To investigate DOG1 expression across diverse histopathological subtypes of CRC.
• To correlate DOG1 expression with immunophenotypes (mucin secretion) and molecular CRC subgroups.
• To assess the prognostic significance of DOG1 in CRC patients.

Main Methods:

• Analysis of 93 CRCs for clinicopathological data, mutations (RAS, BRAF), microsatellite instability (MSI), and mismatch-repair proteins.
• Immunohistochemical profiling for DOG1 and mucin markers (MUC2, MUC5AC, MUC6), CDX2, keratin-20, and keratin-7.
• Univariate and multivariate survival analyses to determine prognostic relevance.

Main Results:

• DOG1 detected in neoplastic cells (45/93) and cancer-associated fibroblasts (CAFs) (41/93) in CRCs.
• High DOG1 in tumor cells associated with gastric-like phenotype, BRAF mutation, MSI-H, or mucinous features, KRAS mutation, and MSS.
• CAF DOG1 expression found in MSS conventional adenocarcinomas; tumor cell DOG1 linked to no adjuvant chemotherapy benefit; CAF DOG1 linked to better overall survival.

Conclusions:

• DOG1 is expressed in a significant proportion of CRCs, in both tumor cells and CAFs.
• Tumor cell DOG1 expression correlates with specific CRC subtypes and molecular features.
• CAF DOG1 expression is a potential biomarker for improved prognosis in CRC.