{"data":{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:24113161", "kind": "science-record", "revision": 8, "content_hash": "sha256:708be96b2ab64b0ed8230699ebaf2f2f1673f8be0cc52096fb391cc20c528b67", "created_at": "2026-11-01T15:40:03Z", "updated_at": "2026-11-01T21:58:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Upregulation of adenylate cyclase 3 (ADCY3) increases the tumorigenic potential of cells by activating the CREB pathway.", "doi": "10.18632/oncotarget.1324", "pmid": "24113161", "authors": ["Seung-Hyun Hong", "Sung-Ho Goh", "Sang Jin Lee", "Jung-Ah Hwang", "Jieun Lee", "Il-Ju Choi", "Hyehyun Seo", "Jong-Hoon Park", "Hiromu Suzuki", "Eiichiro Yamamoto", "In-Hoo Kim", "Jin Sook Jeong", "Mi Ha Ju", "Dong-Hee Lee", "Yeon-Su Lee"], "journal": "Oncotarget", "year": 2013, "abstract": "Adenylate cyclase 3 (ADCY3) is a widely expressed membrane-associated protein in human tissues, which catalyzes the formation of cyclic adenosine-3',5'-monophosphate (cAMP). However, our transcriptome analysis of gastric cancer tissue samples (NCBI GEO GSE30727) revealed that ADCY3 expression was specifically altered in cancer samples. Here we investigated the tumor-promoting effects of ADCY3 overexpression and confirmed a significant correlation between the upregulation of ADCY3 and Lauren's intestinal-type gastric cancers. ADCY3 overexpression increased cell migration, invasion, proliferation, and clonogenicity in HEK293 cells; conversely, silencing ADCY3 expression in SNU-216 cells reduced these phenotypes. Interestingly, ADCY3 overexpression increased both the mRNA level and activity of matrix metalloproteinase 2 (MMP2) and MMP9 by increasing the levels of cAMP and phosphorylated cAMP-responsive element-binding protein (CREB). Consistent with these findings, treatment with a protein kinase A (PKA) inhibitor decreased MMP2 and MMP9 expression levels in ADCY3-overexpressing cells. Knockdown of ADCY3 expression by stable shRNA in human gastric cancer cells suppressed tumor growth in a tumor xenograft model. Thus, ADCY3 overexpression may exert its tumor-promoting effects via the cAMP/PKA/CREB pathway. Additionally, bisulfite sequencing of the ADCY3 promoter region revealed that gene expression was reduced by hypermethylation of CpG sites, and increased by 5-Aza-2'-deoxycytidine (5-Aza-dC)-induced demethylation. Our study is the first to report an association of ADCY3 with gastric cancer as well as its tumorigenic potentials. In addition, we demonstrate that the expression of ADCY3 is regulated through an epigenetic mechanism. Further study on the mechanism of ADCY3 in tumorigenesis will provide the basis as a new molecular target of gastric cancer.", "claims": [{"id": "claim-method", "statement": "The statistical significance of differences between groups was determined using Student's t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:24113161", "locator": "sections[19] \"Statistical analysis\" paragraph 2", "quote": "The statistical significance of differences between groups was determined using Student's t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We performed microarray analyses to compare gene expression profiles of human gastric cancer samples and adjacent normal tissue (NCBI GEO accession no.: GSE30727) [9].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:24113161", "locator": "sections[1] \"INTRODUCTION\" paragraph 3", "quote": "We performed microarray analyses to compare gene expression profiles of human gastric cancer samples and adjacent normal tissue (NCBI GEO accession no.: GSE30727) [9]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The paper used Student's t-test, with P-values below 0.05 considered statistically significant, and obtained microarray source data from NCBI GEO accession GSE30727; its headline result was that “ADCY3 overexpression may exert its tumor-promoting effects via the cAMP/PKA/CREB pathway.”", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:24113161", "locator": "sections[19] \"Statistical analysis\" paragraph 2", "quote": "The statistical significance of differences between groups was determined using Student's t-test. 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Correlation of ADCY3 expression to differentiation grade of tubular adenocarcinoma and signet ring cell carcinoma", "structure": {"pmcid": "PMC3858564", "section_index": 4, "section_title": "Clinicopathological properties of ADCY3 in gastric cancer", "row_count": 8, "column_count": 6}, "table": {"label": null, "caption": "A. 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Correlation of ADCY3 expression to subtypes of gastric carcinoma by Lauren's classification", "structure": {"pmcid": "PMC3858564", "section_index": 4, "section_title": "Clinicopathological properties of ADCY3 in gastric cancer", "row_count": 7, "column_count": 6}, "table": {"label": null, "caption": "B. Correlation of ADCY3 expression to subtypes of gastric carcinoma by Lauren's classification", "rows": [["", "ADCY3 Expression"], ["Lauren classification", "Negative (%)", "Positive (%)", "N"], ["", "", "Mild (%)", "Moderate (%)", "Strong (%)", ""], ["Intestinal", "17(18.7)", "31 (34.1)", "36 (39.5)", "7(7.7)", "91"], ["Mixed", "14(45.2)", "13(41.9)", "3(9.7)", "1(3.2)", "31"], ["Diffuse", "46(56.8)", "23 (28.4)", "9(11.1)", "3(3.7)", "81"], ["N", "77", "67", "48", "11", "203"]], "row_count": 7, "column_count": 6, "numeric_cells": 20, "header_rows": 3, "locator": "section[4]/table-wrap[2]#T2B"}}], "gaps": ["asset:data:geo:GSE30727 not downloaded", "asset:data:geo:GSE30727 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The statistical significance of differences between groups was determined using Student's t-test."}}], "targets": [], "gaps": ["method.student_t"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Cells were cultured in appropriate growth media (Corning Cellgro, M", "k, Seoul, Korea); AGS, KATO III, MKN28, H23, A549, HCT-116, SNU-81, SK-BR-3, JIMT-1, U2OS, and", "H23, A549, HCT-116, SNU-81, SK-BR-3, JIMT-1, U2OS, and U87 (ATCC, Manassas, VA, USA); human de"], "order_basis": "paper_text_order:700", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ession levels in ADCY3-overexpressing cells. Knockdown of ADCY3 expression by stable shRNA in human", "lls. Knockdown of ADCY3 expression by stable shRNA in human gastric cancer cells suppressed tum"], "order_basis": "paper_text_order:1176", "id": "assay:2"}, {"role": "data_generation", "definition_id": "methylation_array", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["via the cAMP/PKA/CREB pathway. Additionally, bisulfite sequencing of the ADCY3 promoter region reve", "tatus of the ADCY3 promoter, genomic DNA was bisulfite-treated using the EZ DNA Methylation-Gold Ki", "assay (MS-HRM) was performed using 10 ng of bisulfite-treated genomic DNA and ResoLight dye in a L", "ed using Gene Scanning software (Roche). 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Records without an assay match currently receive a zero-hour model value.","status":"unverified","severity":"high"},{"code":"signal_score_without_citations","basis":["5,529 of 5,529 records (100.0%) have no citation count from the source metadata."],"claim":"Signal score","gloss":"The signal score uses publication-type weight because the mirror supplied zero citation counts.","detail":"The source supplied no citation counts for any record in this run, so the signal score is publication-type weight only. The citation term of the ranking is inert here, and the shortlist is ordered by publication type alone.","status":"unverified","severity":"high"},{"code":"abstract_absent","basis":["1,667 of 5,529 records (30.2%) carry no abstract at all."],"claim":"Evidence base for classification","gloss":"Some records contain a title and publication type only, defining the available classification evidence.","detail":"Where the mirror contains a title and publication types only, those fields define the classifier evidence. A methods section is required for fuller automated and human review.","status":"unverified","severity":"medium"},{"code":"classifier_agreement_measured","basis":["Published two-way decision agreement 77.7% (310 of 399 decidable records) from a stratified hand-check of 438 real records.","Three-way diagnostic agreement 73.9% (288 of 390 decidable records).","data_only agreement 75.2% (100 of 133 decidable).","48 record(s) could not be decided from title and abstract and were excluded from the denominator.","56 analysis-only records were published under another work type, so the data_only share is not an upper bound."],"claim":"Published automatable decision","gloss":"This figure has been checked against a human reading the same papers, so we know how often it is right.","detail":"The published automatable / not-automatable distribution comes from a rule-based classifier that was hand-checked against a fixed ground-truth definition. The agreement rates below are measured, not estimated. The three-way work type remains a diagnostic and is reported separately.","status":"measured","severity":"high"},{"code":"llm_comparison_not_measured","basis":["rule_based_v1+lex99e1195c7d6f produced 5,529 of 5,529 classifications.","Measured on 438 labelled records; these are RULE-BASED figures, not model results."],"claim":"Rule-based versus LLM agreement","gloss":"Every number here is the rule engine’s own. Model comparison begins when a working API credential is connected and measured.","detail":"The published two-way decision agreed with a human reading on 310 of 399 decidable records (77.7%). The diagnostic three-way label agreed on 288 of 390 decidable records (73.9%). Every percentage in this run belongs to the rule engine. Model comparison begins when a working API credential is connected and measured.","status":"not_measured","severity":"high"},{"code":"confidence_is_a_band","basis":["low band: 135 of 210 hand-judged records were correct, 64.3% [57.6, 70.5] (95% CI).","medium band: 80 of 104 hand-judged records were correct, 76.9% [68.0, 84.0] (95% CI).","high band: 73 of 76 hand-judged records were correct, 96.0% [89.0, 98.7] (95% CI).","A fitted calibrated probability was built, measured and withdrawn: it overstated held-out accuracy and reorders nothing."],"claim":"Confidence band and evidence score","gloss":"The confidence band carries a measured accuracy interval; 0.85 represents relative rank strength.","detail":"Confidence on this run is a BAND plus its measured accuracy interval. The number stored alongside each record is a monotone evidence score that orders records; 0.85 represents relative rank strength. A fitted probability was withdrawn after it overstated held-out accuracy. Threshold on the band.","status":"measured","severity":"medium"},{"code":"three_way_split_is_diagnostic","basis":["The corpus is published at the two-way decision: automatable or not-automatable. The three-way split (data_only / physical / mixed) is published as a diagnostic with its measured reliability attached, not as a claim, because the rule engine's `mixed` call cannot be defended.","The engine called 22 record(s) mixed; 10 matched the human judgement (45.5%, 95% CI 26.9-65.3).","The engine's `mixed` call is right on 10/22 hand-judged records (45.5%, 95% CI 26.9%-65.3%); a constant `physical` guess scores 36.4%.","The engine's `mixed` call does not reliably beat a constant `physical` guess on the hand-judged records it labels mixed.","The sign of that difference flips between two independent samples, so the three-way refinement is not demonstrably informative.","The mixed stratum contributes a disproportionate share of errors relative to its size.","At title-only depth the physical/mixed split collapses: a title says that work was done, not whether it was also analysed."],"claim":"The published decision is two-way","gloss":"The three-way split is shown for diagnosis only. The published split is two ways.","detail":"Count and filter the corpus on automatable versus not-automatable. The data_only / physical / mixed split remains an internal engine diagnostic because the mixed call has lower measured reliability.","status":"measured","severity":"medium"},{"code":"automatable_flag_unproven","basis":["6 of 29 assay families are marked automatable now: meta_analysis, machine_learning, survival_analysis, pca, molecular_docking, differential_expression.","The flag is a rule over assay family and work type; validation begins with the first executed replication.","It inherits the 75.2% data_only agreement rate, because the flag requires the record to be analysis-only."],"claim":"Automatable now","gloss":"This flag marks assay families the rules classify as data-only. The first executed replication will validate it.","detail":"This flag marks families the rules consider replicable from data alone. Its validity depends on the analysis-only classification and will be measured through an executed replication.","status":"unverified","severity":"medium"}],"confidence_policy":"band_with_measured_interval","confidence_contract":{"policy":"band_with_measured_interval","summary":"Confidence is reported as a BAND with a measured accuracy interval. The raw evidence score supplies monotone ordering. A fitted point estimate was withdrawn after it overstated held-out accuracy.","evidence_score":"A monotone evidence score in [0,1] built from cue mass, axis separation and text coverage. Use it to order records. Interpret 0.85 as relative rank strength.","confidence_band":"low | medium | high. Consumers threshold on this value.","band_accuracy":"Wilson 95% interval on the measured agreement of the hand-judged records in this band.","calibrated_confidence":"WITHDRAWN. Reintroduction requires held-out evidence demonstrating reliable estimates across every bin."},"band_accuracy":{"low":{"n":210,"low":0.576,"band":"low","high":0.7046,"agree":135,"accuracy":0.6429},"high":{"n":76,"low":0.8903,"band":"high","high":0.9865,"agree":73,"accuracy":0.9605},"medium":{"n":104,"low":0.6795,"band":"medium","high":0.8397,"agree":80,"accuracy":0.7692}},"provider":"rule_based_v1+lex99e1195c7d6f","lexicon_id":"99e1195c7d6f","contract_published_at":"2026-10-23T12:25:29.022232+00:00","confidence_is_band":true,"confidence_is_probability":false,"decision_taxonomy":"two_way","decidable_fraction_two_way":0.8854,"decidable_fraction_two_way_low":0.8565,"decidable_fraction_two_way_high":0.9143,"decidable_fraction_three_way":0.8586,"decidable_fraction_three_way_low":0.8287,"decidable_fraction_three_way_high":0.8884,"decidable_population":5529,"validation_sample_size":438,"three_way_cost_fraction":0.0268,"three_way_cost_records":148,"decision_counts":{"automatable":230,"not_automatable":5299},"decision_split":{"automatable":{"count":230,"share":0.04159884246699222},"not_automatable":{"count":5299,"share":0.9584011575330078}},"diagnostic_work_type_counts":{"mixed":24,"physical":5275,"data_only":230}}}