Construction of store-operated calcium entry-related gene signature for predicting prognosis and indicates immune microenvironment infiltration in stomach adenocarcinomas.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39333689", "kind": "science-record", "revision": 3, "content_hash": "sha256:0fe2192cf9311b030c9a361329dcbccb9ca6ac5025c1641221c857e4dc9f86bf", "created_at": "2026-11-01T20:29:31Z", "updated_at": "2026-11-01T22:12:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction of store-operated calcium entry-related gene signature for predicting prognosis and indicates immune microenvironment infiltration in stomach adenocarcinomas.", "doi": "10.1038/s41598-024-73324-9", "pmid": "39333689", "authors": ["Zichao Zhang", "Chenglong Wang", "Wenzheng Shi", "Zhihui Wang", "Weihua Fu"], "journal": "Scientific reports", "year": 2024, "abstract": "Gastric adenocarcinoma (STAD) is the most prevalent malignancy of the human digestive system and the fourth leading cause of cancer-related death. Calcium pools, especially Ca2+ entry (SOCE) for storage operations, play a crucial role in maintaining intracellular and extracellular calcium balance, influencing cell activity, and facilitating tumor progression. Nevertheless, the prognostic and immunological value of SOCE in STAD has not been systematically studied. The objective of this study was to develop a risk model for SOCE signature and to explore its correlation with clinical characteristics, prognosis, tumor microenvironment (TME), as well as response to immunotherapy, chemotherapy, and targeted drugs. We used the TCGA, GEO (GSE84437 and GSE159929), cBioPortal and TIMER databases to acquire mRNA expression data for STAD, along with patient clinical indicators, single-cell sequencing data, genomic variation information, and correlations of immune cell infiltration. An analysis of SOCE genes based on tumor vs. normal tissue comparisons, pan-cancer dimension, single-cell sequencing, DNA mutation, and copy number variation revealed that SOCE genes significantly impact the survival of STAD patients and are differentially involved in the immune response. SOCE co-expressed genes were identified by Pearson analysis, and subsequently protein-protein interaction (PPI) and gene function enrichment analysis indicated that coexpressed genes were associated with multicellular pathways. Based on TCGA and GSE84437 datasets, a multifactor Cox proportional hazard regression analysis was conducted to identify SOCE co-expressed genes associated with overall survival in STAD patients. Several mRNA prognostic genes, including PTPRJ, GPR146, LTBP3, FBLN1, EFEMP2, ADAMTS7 and LBH, were identified, which could be used as effective prognostic predictors for STAD patients. In both training and test datasets, receiver operating characteristic (ROC) curves were utilized to evaluate and illustrate the predictive capability of this characteristic in forecasting overall survival of STAD patients. The qPCR and human protein atlas (HPA) were employed to assess mRNA expression and protein levels. Furthermore, the ESTIMATE, TIMER, CIBERSORT, QUANTISEQ, MCPCOUNTER, xCell and EPIC algorithms were utilized to perform immune score and analyze immune cell infiltration. It effectively revealed the difference in prognosis and immune cell infiltration in TME between high-risk and low-risk groups based on the risk signature associated with SOCE. Notably, significant differences in tumor immune dysfunction and rejection (TIDE) scores between the two groups, suggesting that patients in the low-risk group may exhibit a more favorable response to ICIS treatment. The GDSC database and R packages for predictive analysis were utilized to analyze responses to chemotherapy and targeted drugs in high-risk and low-risk groups. In summary, the 7-gene signature associated with SOCE serves as a significant biomarker for evaluating the TME and predicting the prognosis of STAD patients. In addition, it may provide valuable insights for developing effective immunotherapy and chemotherapy regiments for patients with STAD.", "claims": [{"id": "claim-method", "statement": "Then, multivariate COX proportional hazards regression analysis was performed using bivariate regression to screen out genes associated with prognosis in STAD patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39333689", "locator": "sections[9] \"Construction and evaluation of identified prognostic signature\" paragraph 2", "quote": "Then, multivariate COX proportional hazards regression analysis was performed using bivariate regression to screen out genes associated with prognosis in STAD patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during the current study are available in the TCGA (https://xenabrowser.net) and GEO (https://www.ncbi.nlm.nih.gov/geo/) public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. Our study is based on open-source data, so there are no ethical issues and other conflicts of interest.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39333689", "locator": "sections[32] \"notes\" paragraph 1", "quote": "The datasets generated during the current study are available in the TCGA (https://xenabrowser.net) and GEO (https://www.ncbi.nlm.nih.gov/geo/) public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. Our study is based on open-source data, so there are no ethical issues and other conflicts of interest."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The seven-gene SOCE-correlated risk signature stratified STAD patients into groups with significantly different overall survival, with higher risk scores associated with worse prognosis and increased mortality.", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "Survival analysis revealed a significantly higher survival rate in the low-risk group compared to the high-risk group (Logrank P < 0.0001, Fig. 5A)."}, "evidence": [{"asset": "source:pmid:39333689", "locator": "sections[20] \"Establishment of multigene Cox prognostic signature based on SOCE-related genes\" paragraph 3", "quote": "Survival analysis revealed a significantly higher survival rate in the low-risk group compared to the high-risk group (Logrank P < 0.0001, Fig. 5A)."}, {"asset": "source:pmid:39333689", "locator": "sections[20] \"Establishment of multigene Cox prognostic signature based on SOCE-related genes\" paragraph 3", "quote": "The findings suggest that higher the signature prognostic score is associated with worse the prognosis and increased mortality among STAD patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The seven-gene SOCE-correlated risk signature stratified STAD patients into groups with significantly different overall survival, with higher risk scores associated with worse prognosis and increased mortality.", "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:39333689"], "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:GSE159929"], "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:GSE159929"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39333689", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-024-73324-9", "sha256": "sha256:12c6b3539b0ab2103aa694d18299be44faf5f7903f159c86cca1620c357e4953", "bytes": 55604, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-024-73324-9", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11436956", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE159929", "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=GSE159929", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE159929", "version": null, "note": "The datasets generated during the current study are available in the TCGA (https://xenabrowser.net) and GEO (https://www.ncbi.nlm.nih.gov/geo/) public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. Our study is based on open-source data, so there are no ethical issues and other conflicts of interest.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during the current study are available in the TCGA (https://xenabrowser.net) and GEO (https://www.ncbi.nlm.nih.gov/geo/) public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. Our study is based on open-source data, so there are no ethical issues and other conflicts of interest.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4850577", "GSM4850578", "GSM4850579", "GSM4850580", "GSM4850581", "GSM4850582", "GSM4850583", "GSM4850584", "GSM4850585", "GSM4850586", "GSM4850587", "GSM4850588", "GSM4850589", "GSM4850590", "GSM4850591", "GSM4909947", "GSM4909948", "GSM4909949", "GSM4909950", "GSM4909951", "GSM4909952", "GSM4909953", "GSM4909954", "GSM4909955", "GSM4909956", "GSM4909957", "GSM4909958", "GSM4909959", "GSM4909960", "GSM4909961", "GSM4909962", "GSM4909963", "GSM4909964", "GSM4909965", "GSM4909966", "GSM4909967", "GSM4909968", "GSM4909969", "GSM4909970", "GSM4909971", "GSM4909972", "GSM4909973", "GSM4909974", "GSM4909975", "GSM4909976"], "sample_count": 45, "group_sizes": null, "group_sizes_basis": null, "platform": "20795", "taxon": "Homo sapiens", "title": "Single-cell transcriptome profiling of an adult human cell atlas of 15 major organs", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE84437", "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=GSE84437", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE84437", "version": null, "note": "The datasets generated during the current study are available in the TCGA (https://xenabrowser.net) and GEO (https://www.ncbi.nlm.nih.gov/geo/) public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. Our study is based on open-source data, so there are no ethical issues and other conflicts of interest.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during the current study are available in the TCGA (https://xenabrowser.net) and GEO (https://www.ncbi.nlm.nih.gov/geo/) public databases. The patients involved in the database have obtained ethical approval. Users can download relevant data for free for research and publish relevant articles. 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