Journal article
The Status of SOX2 Expression in Gastric Cancers with Induction of CDX2 Defines Groups with Different Genomic Landscapes
Genes, Vol.16(3), p.279
02/26/2025
DOI: 10.3390/genes16030279
PMCID: PMC11942492
PMID: 40149431
Abstract
Gastric adenocarcinoma is a highly lethal neoplasm with a short survival especially when metastatic. Few effective treatments are available for the control of the disease and palliation of patients with metastatic gastric cancer. Although progress has been made in the elucidation of molecular pathways invoked in gastric carcinogenesis, this knowledge has not yet led to major breakthroughs, in contrast to several other types of cancer. The role of stem cell transcription factors SOX2 and CDX2 is of particular interest in the pathogenesis of gastric cancer.
The cohort of gastric adenocarcinomas from The Cancer Genome Atlas (TCGA) was interrogated and two groups of gastric cancers, with CDX2 induction and SOX2 suppression on the one hand and with CDX2 induction and SOX2 maintained expression on the other hand were retained. The induction of expression of the two transcription factors was defined as a mRNA expression z score compared with normal samples above zero. The two groups were compared for clinical-pathologic and genomic differences.
Among gastric cancers with up-regulated CDX2 mRNA, cancers with suppressed SOX2 mRNA were slightly more numerous (55.9%) than those with a maintained SOX2 expression. The SOX2 suppressed group had a higher prevalence of MSI high cancers (30.9% versus 10%) and of cases with high tumor mutation burden (35% versus 12.4%) than cancers with a SOX2 maintained expression, which presented more frequently high Chromosomal Instability (CIN). The group with SOX2 suppression had higher rates of mutations in many gastric cancer-associated genes such as epigenetic modifiers
,
,
, and
, as well as higher rates of mutations in genes encoding for receptor tyrosine kinases
and
. On the other hand,
mutations and amplifications in
,
, and
were more common in the group with a maintained expression of SOX2, approaching significance for
.
Notable differences are present in the genomic landscape of CDX2-induced gastric cancer depending on the level of expression of SOX2 mRNA. Despite this, SOX2 mRNA expression levels were not prognostic.
Details
- Title: Subtitle
- The Status of SOX2 Expression in Gastric Cancers with Induction of CDX2 Defines Groups with Different Genomic Landscapes
- Creators
- Ioannis A Voutsadakis - NOSM University
- Resource Type
- Journal article
- Publication Details
- Genes, Vol.16(3), p.279
- DOI
- 10.3390/genes16030279
- PMID
- 40149431
- PMCID
- PMC11942492
- NLM abbreviation
- Genes (Basel)
- ISSN
- 2073-4425
- eISSN
- 2073-4425
- Publisher
- MDPI; BASEL
- Language
- English
- Date published
- 02/26/2025
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984806511202771
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