CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways
Bibliographic record
Abstract
Background: Colorectal cancer, a prevalent gastrointestinal carcinoma, has a high risk for recurrence when locally advanced and remains lethal when in an advanced stage. Prognostic biomarkers may help in better delineating the aggressiveness of this disease in individual patients and help to tailor appropriate therapies. CDX2, a transcription factor of gastrointestinal differentiation, has been proposed as a biomarker for good outcomes and could also be a marker of specific sub-types amenable to targeted therapies. Methods: Colorectal cancers from The Cancer Genome Atlas (TCGA) colorectal cohort and colon cancers from the Sidra-LUMC AC-ICAM cohort were categorized according to their expressions of CDX2 mRNA. Groups with CDX2 suppression were compared with cancers showing no suppression regarding their clinical and genomic characteristics. Results: CDX2-suppressed colorectal cancers showed a high prevalence of Microsatellite Instability (MSI) and a lower prevalence of chromosomal Instability (CIN) compared to non-CDX2-suppressed cancers. In addition, CDX2-suppressed cancers had a higher prevalence of mutations in several receptor tyrosine kinase genes, including EGFR, ERBB3, ERBB4, RET, and ROS1. In contrast, CDX2-suppressed cancers displayed lower mutation frequencies than non-CDX2-suppressed cancers in the genes encoding for the two most frequently mutated tumor suppressors, APC and TP53, and the most frequently mutated colorectal cancer oncogene, KRAS. However, CDX2-suppressed colorectal cancers had a higher prevalence of mutations in alternative genes of the WNT/APC/β-catenin and KRAS/BRAF/MEK pathways. In addition, they showed frequent mutations in DNA damage response (DDR) genes, such as BRCA2 and ATM. Conclusion: CDX2-suppressed colorectal cancers constitute a genomically distinct subset of colon and rectal cancers that have a lower prevalence of KRAS, APC, and TP53 mutations, but a high prevalence of mutations in less commonly mutated colorectal cancer genes. These alterations could serve as targets for personalized therapeutics in this subset.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".