{
  "schema_version": "1.0.0",
  "evidence_release": "public-evidence-v1-2026-08-26",
  "case_id": "egfr-colorectal-case-v1",
  "question": "What role does epiregulin and amphiregulin play in the use of EGFR inhibitors for colorectal cancer?",
  "question_type": "summary",
  "structured_input": {
    "genes": [
      {"symbol": "AREG", "ncbi_gene_id": 374},
      {"symbol": "EREG", "ncbi_gene_id": 2069},
      {"symbol": "EGFR", "ncbi_gene_id": 1956}
    ],
    "species": [],
    "species_interpretation": "No species was explicitly specified in the question; species annotations remain publication-level context rather than a hard filter",
    "context": ["colorectal cancer", "EGFR inhibitor treatment", "biomarker role"]
  },
  "retrieval": {
    "candidate_generation": "PubTator gene links plus disjoint exact-symbol fallback",
    "candidate_count": 277638,
    "coverage_tier_counts": {"one_of_three": 263702, "two_of_three": 12423, "three_of_three": 1513},
    "ranking_policy": "coverage_then_semantic",
    "ordering": ["requested gene coverage descending", "semantic similarity descending", "PMID ascending as deterministic tie-breaker"],
    "semantic_similarity_is_evidence_strength": false,
    "returned_top_k": 10,
    "selected_count": 5,
    "annotation_scope": "PubTator document-level; section unspecified"
  },
  "selected_publications": [
    {"pmid": "40727266", "title": "Exploring the Potential of Epiregulin and Amphiregulin as Prognostic, Predictive, and Therapeutic Targets in Colorectal Cancer."},
    {"pmid": "33775193", "title": "Immunohistochemical evaluation of the prognostic and predictive power of epidermal growth factor receptor ligand levels in patients with metastatic colorectal cancer."},
    {"pmid": "30252132", "title": "Epigenetic regulation of Amphiregulin and Epiregulin in colorectal cancer."},
    {"pmid": "19738126", "title": "Amphiregulin and epiregulin mRNA expression in primary tumors predicts outcome in metastatic colorectal cancer treated with cetuximab."},
    {"pmid": "32943459", "title": "Amphiregulin Expression Is a Predictive Biomarker for EGFR Inhibition in Metastatic Colorectal Cancer: Combined Analysis of Three Randomized Trials."}
  ],
  "generated_output": {
    "status": "model_generated_not_expert_validated",
    "evidence_scope": "abstract-reported",
    "direct_answer": "Epiregulin (EREG) and amphiregulin (AREG) play a predictive role in the response to EGFR inhibitors in colorectal cancer, particularly in KRAS wild-type tumors. Their expression levels are associated with improved outcomes, including progression-free survival and overall survival, when treated with anti-EGFR therapies such as cetuximab.",
    "claims": [
      {"claim_id": 1, "text": "AREG and EREG expression levels in primary tumors are predictive of response to anti-EGFR therapies in KRAS wild-type metastatic colorectal cancer.", "pmids": ["19738126", "32943459"], "stance": "supports", "species_context": "human"},
      {"claim_id": 2, "text": "High AREG mRNA expression is associated with improved overall survival and progression-free survival in metastatic colorectal cancer patients treated with anti-EGFR therapies.", "pmids": ["32943459"], "stance": "supports", "species_context": "human"},
      {"claim_id": 3, "text": "EREG positivity is associated with longer overall survival in patients with metastatic colorectal cancer treated with EGFR inhibitors, particularly in those with left-sided primary tumors.", "pmids": ["40727266"], "stance": "supports", "species_context": "human"},
      {"claim_id": 4, "text": "AREG and EREG are regulated by epigenetic mechanisms, including gene-body methylation, which can influence their expression and response to EGFR-targeted therapies.", "pmids": ["30252132"], "stance": "supports", "species_context": "human"}
    ]
  },
  "deterministic_validation": {
    "status": "passed",
    "checks": ["output schema", "claim citation presence", "citation membership in selected evidence", "stance values", "run and model provenance"],
    "boundary": "Passing deterministic checks establishes structural validity, not scientific support"
  },
  "automated_judge_finding": {
    "status": "provisional_failure_case",
    "claim_id": 3,
    "returned_assessment": {
      "judgment": "supported",
      "citation_support": "moderate",
      "context_match": "partial",
      "contradiction_handling": "none",
      "overstatement_risk": "low",
      "evidence_scope": "abstracts_only",
      "pmids": ["33775193"],
      "rationale": "The provided evidence shows that EREG positivity is associated with longer overall survival in patients with metastatic colorectal cancer treated with EGFR inhibitors, particularly in those with left-sided primary tumors, as reported in the study with PMID 33775193."
    },
    "synthesis_cited_pmids": ["40727266"],
    "judge_assessed_pmids": ["33775193"],
    "failure": "The judge treated support in another selected publication as support for the claim, instead of auditing only the claim's cited publication",
    "product_action": "Restrict claim-level judging to cited evidence, capture this case in an adversarial judge benchmark, and require expert calibration before using judge labels as quality evidence"
  },
  "historical_model_provenance": {
    "generator": {"model": "Qwen/Qwen3-8B", "revision": "b968826d9c46dd6066d109eabc6255188de91218", "temperature": 0, "max_output_tokens": 1024},
    "judge": {"model": "mistralai/Mistral-7B-Instruct-v0.3", "revision": "c170c708c41dac9275d15a8fff4eca08d52bab71", "temperature": 0, "max_output_tokens": 2048}
  },
  "assessment": {
    "expert_review": "not_completed",
    "release_readiness": "not_assessed",
    "recommendation": "Use as a development and evaluator-failure case, not as validated biomedical guidance"
  },
  "source_artifact_sha256": {
    "prepared_case": "19aacc41ba9dd61efee5a5747b210a63e558371baafb023a6c79cba95c1d1480",
    "synthesis_record": "02a1ced2a15db0841a4868f30edc1bbb9a9e502a8a17dfb8df66779c8da32909",
    "deterministic_evaluation": "d1b8b56b7aff74805a867d8c3ec67b44e9cdfa9bdf86090e5236d3dd371183b6",
    "judge_record": "49cd8d6221cccfc3550cedbc32d4e1b9cc9f55c3219f0b38eed763e02bc8e1a4"
  }
}