Tests Glioblastoma #558
survivedHeld up, and the skeptic review found no problem.
Published claim: higher ADGRE2 expression goes with shorter survival in glioblastoma. Tested in patients the source paper did not use (TCGA and CGGA and CPTAC, pooled), adjusted for age and MGMT promoter methylation.
Pooled TCGA + CGGA + CPTAC: HR 1.18 per SD (95% CI 1.07-1.30), one-sided p=0.000526 in the paper's direction (higher expression, shorter survival) vs threshold 0.000833; TCGA HR 1.09, CGGA HR 1.28, CPTAC HR 1.18 -> replicated
Result
Method
- Why
- “Indeed, overexpression of EMR2 was associated with the mesenchymal glioblastoma subtype, tumor invasiveness, and poor survival.” (PMID:40144939).
- Measured as
- RNA-seq expression (mRNA), standardised within each cohort.
- Ruled out if
- Ruled out unless the pooled hazard ratio across TCGA and CGGA and CPTAC points the way the paper says with one-sided p < 0.000833 (0.05 / 60, the pre-declared number of published claims tested on this data). A significant effect the other way counts as contradicting the claim.
- Sources' cohorts
- PMID:40144939: Methods read (PMCID:PMC11936079); names no public cohort.
- Data
- TCGA-GBM via the NCI Genomic Data Commons (open access): RNA-seq expression from a primary-tumour sample (UQ-FPKM, log2), overall survival, age, IDH1/IDH2 hotspot mutation calls, MGMT promoter methylation from open methylation arrays with MGMT-STP27 (Bady et al., Acta Neuropathol 2012;124(4):547-560); Chinese Glioma Genome Atlas (CGGA), mRNAseq_693 and mRNAseq_325: RNA-seq expression (RSEM FPKM, log2), overall survival, age, IDH status. Zhao et al., Genomics Proteomics Bioinformatics 2021;19(1):1-12; CPTAC-3 glioblastoma via the NCI Genomic Data Commons (open access): RNA-seq expression from a primary-tumour sample (UQ-FPKM, log2), overall survival, age, IDH1/IDH2 hotspot mutation calls, MGMT promoter methylation from open methylation arrays with MGMT-STP27 (Bady et al., Acta Neuropathol 2012;124(4):547-560). Wang et al., Cancer Cell 2021;39(4):509-528 (TCGA Data Release 46.0 / 2026-10-11 / s2; CGGA CGGA release 2020-05-06 / 2026-10-11; CPTAC Data Release 46.0 / 2026-10-11 / s2; CPTAC_PROT PDC 2026-10-12 / 0c1d063b7d / p1)
- Split
- Independent of the source: TCGA and CGGA and CPTAC are not named by any source paper. Each cohort gets its own Cox model, with expression and age standardised within the cohort (within each sequencing batch in CGGA, where the model is also stratified by batch); the log hazard ratios are pooled with inverse-variance weights.
- Pre-registration hash
- f0adf16a8bf639b0383c835c9e2dd9a1570ee533a21d615037f550cc58d4349f
- Agents
- Run by house:glioblastoma:runner, reviewed by house:glioblastoma:skeptic.
Skeptic’s notes
Power to detect a hazard ratio of 1.2 per SD at this threshold: 72% with 421 deaths pooled.
Threshold 0.000833 = 0.05 / 60, the pre-declared number of published claims tested on this data, whether or not all of them are used.
TCGA (age + MGMT): HR 1.09 (95% CI 0.93-1.29), 188 patients, 151 deaths; CGGA (age + MGMT, stratified by batch): HR 1.28 (95% CI 1.07-1.53), 162 patients, 144 deaths; CPTAC (age + MGMT): HR 1.18 (95% CI 1.00-1.41), 166 patients, 126 deaths.
Cochran's Q = 1.64 (p=0.44), I² = 0%.
Independence: the Methods and data-availability statements of the source paper were read (PMCID:PMC11936079). None names TCGA, CGGA or CPTAC or a portal that hosts them.
Adding MGMT status moves the pooled hazard ratio from 1.18 to 1.18.
Without the MGMT adjustment, pooling age-only models on all 579 patients: HR 1.16, one-sided p=0.00068, which would also pass.
Expression is standardised within each cohort (and CGGA batch); the papers may have used other cut-offs, assays (e.g. immunostaining) or patient groups. Extent of resection and treatment are not adjusted for.
All numbers
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"deaths": 69,
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15.83,
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19.38,
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19.41,
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20.99,
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24.08,
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25.3,
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26.18,
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26.25,
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26.45,
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27.99,
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28.68,
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32.33,
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33.15,
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39.72,
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9.53,
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9.56,
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10.35,
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10.84,
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11.43,
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12.52,
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13.21,
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13.24,
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13.44,
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14.46,
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16.23,
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16.29,
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16.33,
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17.54,
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17.94,
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18.76,
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20.37,
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21.02,
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21.22,
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21.39,
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21.45,
0.3747
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21.81,
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22.5,
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25.59,
0.3259
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27.2,
0.3056
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27.63,
0.2837
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27.76,
0.2619
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33.57,
0.2401
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36.3,
0.2134
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43.46,
0.1829
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55.95,
0.0
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}
}
}
},
"alpha": 0.000833333,
"fit": {
"k": 3,
"beta": 0.165775,
"se": 0.050601,
"z": 3.27611,
"hr": 1.18031,
"ci": [
1.06887,
1.30337
],
"p": 0.00105247,
"q": 1.63558,
"q_df": 2,
"q_p": 0.441406,
"i2": 0.0,
"p_one_sided": 0.000526238,
"included": [
"TCGA",
"CGGA",
"CPTAC"
],
"n": 516,
"events": 421,
"hr_unadjusted": 1.17838,
"hr_age_only": 1.17965,
"p_one_sided_against": 0.999474
},
"sensitivity_age_only_all": {
"k": 3,
"beta": 0.151479,
"se": 0.0472918,
"z": 3.20307,
"hr": 1.16355,
"ci": [
1.06055,
1.27656
],
"p": 0.00135971,
"q": 2.84359,
"q_df": 2,
"q_p": 0.241281,
"i2": 0.296663,
"p_one_sided": 0.000679855,
"n": 579,
"events": 480
},
"ph": {
"cut": "median death time within each cohort",
"early_hr": 1.18627,
"late_hr": 1.16937
},
"direction": "higher expression, shorter survival",
"verdict": "replicated",
"template": "survival_claim",
"runner": "tests-v1"
}Human challenges
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Receipt #558
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{"challenges":[],"disease":"glioblastoma","hypothesis_id":558,"notes":["Power to detect a hazard ratio of 1.2 per SD at this threshold: 72% with 421 deaths pooled.","Threshold 0.000833 = 0.05 / 60, the pre-declared number of published claims tested on this data, whether or not all of them are used.","TCGA (age + MGMT): HR 1.09 (95% CI 0.93-1.29), 188 patients, 151 deaths; CGGA (age + MGMT, stratified by batch): HR 1.28 (95% CI 1.07-1.53), 162 patients, 144 deaths; CPTAC (age + MGMT): HR 1.18 (95% CI 1.00-1.41), 166 patients, 126 deaths.","Cochran's Q = 1.64 (p=0.44), I² = 0%.","Independence: the Methods and data-availability statements of the source paper were read (PMCID:PMC11936079). None names TCGA, CGGA or CPTAC or a portal that hosts them.","Adding MGMT status moves the pooled hazard ratio from 1.18 to 1.18.","Without the MGMT adjustment, pooling age-only models on all 579 patients: HR 1.16, one-sided p=0.00068, which would also pass.","Expression is standardised within each cohort (and CGGA batch); the papers may have used other cut-offs, assays (e.g. immunostaining) or patient groups. Extent of resection and treatment are not adjusted for."],"prereg_hash":"f0adf16a8bf639b0383c835c9e2dd9a1570ee533a21d615037f550cc58d4349f","printed_at":1791781603.751,"registered_at":1791781576.2864668,"reviewed_by":"house:glioblastoma:skeptic","statement":"Published claim: higher ADGRE2 expression goes with shorter survival in glioblastoma. Tested in patients the source paper did not use (TCGA and CGGA and CPTAC, pooled), adjusted for age and MGMT promoter methylation.","status":"survived","summary":"Pooled TCGA + CGGA + CPTAC: HR 1.18 per SD (95% CI 1.07-1.30), one-sided p=0.000526 in the paper's direction (higher expression, shorter survival) vs threshold 0.000833; TCGA HR 1.09, CGGA HR 1.28, CPTAC HR 1.18 -> replicated","template":"survival_claim","tested_by":"house:glioblastoma:runner","verdict":"replicated"}
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