SYPL1 Inhibits Apoptosis in Pancreatic Ductal Adenocarcinoma via Suppression of ROS-Induced ERK Activation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33042794", "kind": "science-record", "revision": 6, "content_hash": "sha256:01701f2f4ca0d6e1b17b1928337cbdeb88c01819b07a3955c3d95503c842e9c3", "created_at": "2026-11-01T15:41:12Z", "updated_at": "2026-11-01T21:23:56Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "SYPL1 Inhibits Apoptosis in Pancreatic Ductal Adenocarcinoma via Suppression of ROS-Induced ERK Activation.", "doi": "10.3389/fonc.2020.01482", "pmid": "33042794", "authors": ["Yunda Song", "Xuesong Sun", "Fangting Duan", "Chaobin He", "Jiali Wu", "Xin Huang", "Kaili Xing", "Shuxin Sun", "Ruiqi Wang", "Fengxiao Xie", "Yize Mao", "Jun Wang", "Shengping Li"], "journal": "Frontiers in oncology", "year": 2020, "abstract": "Synaptophysin-like 1 (SYPL1) is a neuroendocrine-related protein. The role of SYPL1 in pancreatic ductal adenocarcinoma (PDAC) and the underlying molecular mechanism remain unclarified. Here, after analyzing five datasets (GSE15471, GSE16515, GSE28735, TCGA, and PACA-AU) and 78 PDAC patients from Sun Yat-sen University Cancer Center, we demonstrated that SYPL1 was upregulated in PDAC and that a high level of SYPL1 indicated poor prognosis. Bioinformatics analysis implied that SYPL1 was related to cell proliferation and cell death. To validate these findings, gain-of-function and loss-of-function experiments were carried out, and we found that SYPL1 promoted cell proliferation in vitro and in vivo and that it protected cells from apoptosis. Mechanistic studies revealed that sustained extracellular-regulated protein kinase (ERK) activation was responsible for the cell death resulting from knockdown of SYPL1. In addition, bioinformatics analysis showed that the expression of SYPL1 positively correlated with antioxidant activity. Reactive oxygen species (ROS) were upregulated in cells with SYPL1 knockdown and vice versa. Upregulated ROS led to ERK activation and cell death. These results suggest that SYPL1 plays a vital role in PDAC and promotes cancer cell survival by suppressing ROS-induced ERK activation.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate analysis using the COX model showed that the grade of PDAC (hazard ratio [HR]: 2.924, 95% confidence interval [CI]: 1.291–6.621), tumor size (HR: 3.900, 95% CI: 1.114–13.645) and the expression level of SYPL1 (HR: 2.807, 95% CI: 1.204–6.543) were independent prognostic factors for patients in the SYSUCC (Table 2).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33042794", "locator": "sections[15] \"Elevated SYPL1 Indicates Poor Prognosis\" paragraph 2", "quote": "Univariate and multivariate analysis using the COX model showed that the grade of PDAC (hazard ratio [HR]: 2.924, 95% confidence interval [CI]: 1.291–6.621), tumor size (HR: 3.900, 95% CI: 1.114–13.645) and the expression level of SYPL1 (HR: 2.807, 95% CI: 1.204–6.543) were independent prognostic factors for patients in the SYSUCC (Table 2)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33042794", "locator": "sections[22] \"Data Availability Statement\" paragraph 2", "quote": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33042794"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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Yat-sen University Cancer Center.", "structure": {"pmcid": "PMC7522464", "section_index": 3, "section_title": "Patients and Tissue Specimens", "row_count": 28, "column_count": 5}, "table": {"label": "Table 1", "caption": "Characteristics of pancreatic ductal adenocarcinoma patients from Sun Yat-sen University Cancer Center.", "rows": [["Clinicopathological features", "n", "SYPL1 expression", "p-values"], ["", "", "Low (n = 30)", "High (n = 48)", ""], ["Sex", "", "", "", "0.744"], ["Male", "45", "18", "27", ""], ["Female", "33", "12", "21", ""], ["Age", "", "58.000 ± 9.229", "59.042 ± 11.123", "0.669"], ["Tumor site", "", "", "", "0.532"], ["Head of pancreas", "65", "24", "41", ""], ["Body and tail", "13", "6", "7", ""], ["Grade", "", "", "", "0.607"], ["Moderate to good", "35", "12", "23", ""], ["Poor to poor-moderate", "39", "17", "22", ""], ["Not determine", "4", "1", "3", ""], ["Tumor diameter (cm)", "", "4.0 (3.0–5.0)", "3.0 (3.0–4.5)", "0.31"], ["Tumor extends beyond pancreas", "", "", "", "0.767"], ["Presence", "62", "25", "37", ""], ["Absence", "12", "4", "8", ""], ["Not determine", "4", "1", "3", ""], ["Nodal status", "", "", "", "0.590"], ["Positive", "36", "15", "21", ""], ["Negative", "42", "15", "27", ""], ["Positive lymph node", "", "0.5 (0.0–2.0)", "0 (0.0–1.0)", "0.398"], ["Perineural invasion", "", "", "", "0.045"], ["Presence", "59", "19", "40", ""], ["Absence", "19", "11", "8", ""], ["Microvascular invasion", "", "", "", "0.713"], ["Presence", "21", "9", "12", ""], ["Absence", "44", "21", "23", ""]], "row_count": 28, "column_count": 5, "numeric_cells": 66, "header_rows": 2, "locator": "section[3]/table-wrap[1]#T1"}}, {"id": "asset:table:pmid:33042794:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:7065b096225241dbc24d3610a47bfdfbd8b52147235093acf59b466404f2226f", "bytes": 1074, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[15]/table-wrap[1]#T2", "version": null, "note": "Univariate and multivariate Cox regression analysis for patients from Sun Yat-sen University Cancer Center.", "structure": {"pmcid": "PMC7522464", "section_index": 15, "section_title": "Elevated SYPL1 Indicates Poor Prognosis", "row_count": 12, "column_count": 7}, "table": {"label": "Table 2", "caption": "Univariate and multivariate Cox regression analysis for patients from Sun Yat-sen University Cancer Center.", "rows": [["", "Univariate analysis", "Multivariate analysis"], ["", "HR", "95% CI", "p-values", "HR", "95% CI", "p-values"], ["Sex", "1.257", "0.643–2.459", "0.504", "", "", ""], ["Age", "1.017", "0.982–1.054", "0.341", "", "", ""], ["Location", "1.387", "0.573–3.356", "0.468", "", "", ""], ["Grade (poor to poor-moderate)", "2.447", "1.214–4.935", "0.012", "2.924", "1.291–6.621", "0.010"], ["Diameter (>2.75 cm)", "5.282", "1.607–17.365", "0.006", "3.900", "1.114–13.645", "0.033"], ["Tumor extends beyond 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{"score": 1.0, "band": "verbatim", "quote": "Univariate and multivariate analysis using the COX model showed that the grade of PDAC (hazard ratio [HR]: 2.924, 95% confidence interval [CI]: 1.291–6.621), tumor size (HR: 3.900, 95% CI: 1.114–13.645) and the expression level of SYPL1 (HR: 2.807, 95% CI: 1.204–6.543) were independent prognostic factors for patients in the SYSUCC (Table 2)."}}], "targets": [], "gaps": []}, "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": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE15471", "GSE16515", "and GSE28735"], "resolved_accessions": ["GSE15471", "GSE16515"], "statements": ["The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation."], "basis": "The paper names GSE15471, GSE16515 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:33042794", "data:geo:GSE15471", "asset:table:pmid:33042794:1", "asset:table:pmid:33042794:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE15471"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:23:23Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 38601, "completion_tokens": 2418, "cached_tokens": 640}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:33042794", "type": "paper", "label": "pmid:33042794"}, {"id": "source:pmid:33042794", "type": "manuscript", "label": "PMID 33042794 full text"}, {"id": "data:geo:GSE15471", "type": "dataset", "label": "GEO GSE15471"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33042794", "type": "paper", "label": "pmid:33042794"}, {"id": "source:pmid:33042794", "type": "manuscript", "label": "PMID 33042794 full text"}, {"id": "data:geo:GSE15471", "type": "dataset", "label": "GEO GSE15471"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33042794", "type": "extraction", "used": ["source:pmid:33042794"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE15471", "type": "accession_resolution", "used": ["data:geo:GSE15471"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:33042794", "parent_hash": "sha256:e3ab27e58448d41c720707f139af054b95aa03459910d12f6f4dc630da561484", "fork_of": null, "generation": 5}, "gaps": ["asset:data:geo:GSE15471 licence not read", "asset:data:geo:GSE15471 not downloaded", "asset:data:geo:GSE16515 licence not read", "asset:data:geo:GSE16515 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["SYPL1 Inhibits Apoptosis in Pancreatic Ductal Adenocarcinoma via Supp", "and in vivo and that it protected cells from apoptosis. Mechanistic studies revealed that sustained"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["PL1 promoted cell proliferation in vitro and in vivo and that it protected cells from apoptosis.", "Six-weeks-old Crj:BALB/c female athymic nude mice were purchased from Vital River (Beijing, China).", "× length × width × width). After 5–7 weeks, mice were euthanized, and xenografts were removed, wei"], "order_basis": "paper_text_order:761", "id": "assay:2"}, {"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": ["esponsible for the cell death resulting from knockdown of SYPL1. In addition, bioinformatics analys", "s (ROS) were upregulated in cells with SYPL1 knockdown and vice versa. Upregulated ROS led to ERK a", "n University Cancer Center. Cell Culture and Transfection BxPC-3, CFPAC-1, and PANC-1 human PDAC cell", "siRNA (RiboBio, Guangzhou, China), which was transfected into cells by Lipofectamine 2000 (Invitrogen"], "order_basis": "paper_text_order:963", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Univariate and multivariate analysis using the COX model showed that the grade of PDAC (hazard ratio [HR]: 2.924, 95% confidence interval [CI]: 1.291–6.621), tumor size (HR: 3.900, 95% CI: 1.114–13.645) and the expression level of SYPL1 (HR: 2.807, 95% CI: 1.204–6.543) were independent prognostic factors for patients in the SYSUCC (Table 2)."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}