Analysis of cancer-promoting genes related to chemotherapy resistance in esophageal squamous cell carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35282117", "kind": "science-record", "revision": 4, "content_hash": "sha256:8e37b32070429b65bf6f06da6c30fa3342fd7e3ab8ec33b644671a7d9763f608", "created_at": "2026-11-01T18:14:04Z", "updated_at": "2026-11-01T22:06:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of cancer-promoting genes related to chemotherapy resistance in esophageal squamous cell carcinoma.", "doi": "10.21037/atm-21-7032", "pmid": "35282117", "authors": ["Feng Xie", "Donglei Zhang", "Xiaoqing Qian", "Huabing Wei", "Lihuang Zhou", "Chunyong Ding", "Wenbiao Pan", "Qing Ye"], "journal": "Annals of translational medicine", "year": 2022, "abstract": "Background: According to histopathology, esophageal cancer can be divided into squamous cell carcinoma (SCC) and esophageal adenocarcinoma (adeno arcinoma). In China, 90% of esophageal cancer patients are squamous cell carcinoma. Cisplatin and fluaziridine are the main chemotherapy before and after surgery. Long-term drug treatment is often accompanied by the emergence of drug resistance of tumor cells. There are many mechanisms for the emergence of drug resistance of tumor cells, including the increase of drug efflux, the decrease of drug intake, the inhibition of cell apoptosis, and so on. This study aimed to investigate the key cancer-promoting genes related to chemotherapy resistance in esophageal squamous cell carcinoma (ESCC).\nMethods: Two datasets from the Gene Expression Omnibus (GEO) database (GSE86099 and GSE50224) were retrieved. We performed microRNA (miRNA) and messenger RNA (mRNA) expression analysis to identify differentially expressed genes (DEGs). The intersection of the downregulated miRNA targets and the upregulated mRNAs were used for Gene Ontology (GO) enrichment analysis, and survival risk was assessed using data from The Cancer Genome Atlas (TCGA).\nResults: There were 35 common genes, of which, based on GO enrichment, most were related to the cardiac muscle cell action. Four genes showed significant association with the estimated half-maximal inhibitory concentration (IC50) of paclitaxel: bone morphogenetic protein 1 (BMP1), dumbbell former 4 protein (DBF4), angiogenin (ANG), and MAP7 domain containing 2 (MAP7D2). Four risk factors (MP1, HIP1, ANG, and MAP7D2) were selected to generate a signature using least absolute shrinkage and selection operator (LASSO) regression. Protein-protein interaction (PPI) analysis showed guanine nucleotide-binding protein subunit beta 4 (GNB4), calcium voltage-gated channel auxiliary subunit beta 2 (CACNB2), and sodium voltage-gated channel alpha subunit 1 (SCN1A) were located at key positions of the network. Among potential risk genes, only the high expression of dedicator of cytokinesis 8 (DOCK8) was associated with poorer survival.\nConclusions: The 35 oncogenes may be involved in mechanisms of chemotherapy resistance in ESCC, as well as the corresponding enrichment and regulatory network. The signature containing 4 key risk genes merits further investigation and may provide a deeper understanding of the molecular mechanisms in ESCC treatment failure.", "claims": [{"id": "claim-method", "statement": "After screening the essential ESCC-associated genes involved in both chemotherapy resistance and survival, least absolute shrinkage and selection operator (LASSO) Cox regression was performed to identify relevant risk genes, using 10-fold cross-validation, and the prognostic predictive signature, using the R software package glmnet (v 4.1-1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35282117", "locator": "sections[7] \"Prognostic predictive signature\" paragraph 2", "quote": "After screening the essential ESCC-associated genes involved in both chemotherapy resistance and survival, least absolute shrinkage and selection operator (LASSO) Cox regression was performed to identify relevant risk genes, using 10-fold cross-validation, and the prognostic predictive signature, using the R software package glmnet (v 4.1-1)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "There were two available arrays with chemotherapy-resistant ESCC samples: GSE86099 (gene expression signature of paclitaxel resistance in human ESCC cell lines) and GSE50224 (the expression profiling of miRNA from chemotherapy-resistant esophageal adenosquamous carcinoma cell line).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35282117", "locator": "sections[3] \"Microarray data\" paragraph 3", "quote": "There were two available arrays with chemotherapy-resistant ESCC samples: GSE86099 (gene expression signature of paclitaxel resistance in human ESCC cell lines) and GSE50224 (the expression profiling of miRNA from chemotherapy-resistant esophageal adenosquamous carcinoma cell line)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The four-gene risk signature achieved an AUC of 0.856 for 2-year survival prediction.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "In particular, the AUC value for the 2-year survival evaluation was 0.856 (95% CI: 0.742−0.969)."}, "evidence": [{"asset": "source:pmid:35282117", "locator": "sections[17] \"Prognostic performance of the signature\" paragraph 2", "quote": "In particular, the AUC value for the 2-year survival evaluation was 0.856 (95% CI: 0.742−0.969)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The four-gene risk signature achieved an AUC of 0.856 for 2-year survival prediction.", "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:35282117"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE50224"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE50224"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35282117", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm-21-7032", "sha256": "sha256:545ee8603e691e1eba6cac667861c21b2e60a5c0503aaf7bdeb9edc158b12a08", "bytes": 39042, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/atm-21-7032", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8848450", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE50224", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE50224", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE50224", "version": null, "note": "There were two available arrays with chemotherapy-resistant ESCC samples: GSE86099 (gene expression signature of paclitaxel resistance in human ESCC cell lines) and GSE50224 (the expression profiling of miRNA from chemotherapy-resistant esophageal adenosquamous carcinoma cell line).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "There were two available arrays with chemotherapy-resistant ESCC samples: GSE86099 (gene expression signature of paclitaxel resistance in human ESCC cell lines) and GSE50224 (the expression profiling of miRNA from chemotherapy-resistant esophageal adenosquamous carcinoma cell line).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1216060", "GSM1216061", "GSM1216062", "GSM1216063", "GSM1216064", "GSM1216065", "GSM1216066", "GSM1216067", "GSM1216068", "GSM1216069", "GSM1216070", "GSM1216071", "GSM1216072", "GSM1216073", "GSM1216074", "GSM1216075", "GSM1216076", "GSM1216077", "GSM1216078", "GSM1216079", "GSM1216080", "GSM1216081", "GSM1216082", "GSM1216083", "GSM1216084", "GSM1216085", "GSM1216086", "GSM1216087", "GSM1216088", "GSM1216089", "GSM1216090", "GSM1216091", "GSM1216092", "GSM1216093", "GSM1216094", "GSM1216095"], "sample_count": 36, "group_sizes": null, "group_sizes_basis": null, "platform": "8786", "taxon": "synthetic construct; 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