The Status of SOX2 Expression in Gastric Cancers with Induction of CDX2 Defines Groups with Different Genomic Landscapes
Bibliographic record
Abstract
Background: 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. Methods: 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. Results: 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 ARID1A, KMT2D, KMT2C, and KMT2B, as well as higher rates of mutations in genes encoding for receptor tyrosine kinases ERBB4 and FGFR1. On the other hand, TP53 mutations and amplifications in MYC, ERBB2, and CCNE1 were more common in the group with a maintained expression of SOX2, approaching significance for MYC. Conclusions: 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".