Identification of a 5-Gene-Based Scoring System by WGCNA and LASSO to Predict Prognosis for Rectal Cancer Patients.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33833937", "kind": "science-record", "revision": 7, "content_hash": "sha256:b0773a53183b12c56b2aa883364d25f013ac003a80f401478ad42e5e83f8e149", "created_at": "2026-11-01T15:41:31Z", "updated_at": "2026-11-01T22:03:31Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a 5-Gene-Based Scoring System by WGCNA and LASSO to Predict Prognosis for Rectal Cancer Patients.", "doi": "10.1155/2021/6697407", "pmid": "33833937", "authors": ["He Huang", "Shilei Xu", "Aidong Chen", "Fen Li", "Jiezhong Wu", "Xusheng Tu", "Kunpeng Hu"], "journal": "Analytical cellular pathology (Amsterdam)", "year": 2021, "abstract": "BACKGROUND: Although accumulating evidence suggested that a molecular signature panel may be more effective for the prognosis prediction than routine clinical characteristics, current studies mainly focused on colorectal or colon cancers. No reports specifically focused on the signature panel for rectal cancers (RC). Our present study was aimed at developing a novel prognostic signature panel for RC.\nMETHODS: Sequencing (or microarray) data and clinicopathological details of patients with RC were retrieved from The Cancer Genome Atlas (TCGA-READ) or the Gene Expression Omnibus (GSE123390, GSE56699) database. A weighted gene coexpression network was used to identify RC-related modules. The least absolute shrinkage and selection operator analysis was performed to screen the prognostic signature panel. The prognostic performance of the risk score was evaluated by survival curve analyses. Functions of prognostic genes were predicted based on the interaction proteins and the correlation with tumor-infiltrating immune cells. The Human Protein Atlas (HPA) tool was utilized to validate the protein expression levels.\nRESULTS: A total of 247 differentially expressed genes (DEGs) were commonly identified using TCGA and GSE123390 datasets. Brown and yellow modules (including 77 DEGs) were identified to be preserved for RC. Five DEGs (ASB2, GPR15, PRPH, RNASE7, and TCL1A) in these two modules constituted the optimal prognosis signature panel. Kaplan-Meier curve analysis showed that patients in the high-risk group had a poorer prognosis than those in the low-risk group. Receiver operating characteristic (ROC) curve analysis demonstrated that this risk score had high predictive accuracy for unfavorable prognosis, with the area under the ROC curve of 0.915 and 0.827 for TCGA and GSE56699 datasets, respectively. This five-mRNA classifier was an independent prognostic factor. Its predictive accuracy was also higher than all clinical factor models. A prognostic nomogram was developed by integrating the risk score and clinical factors, which showed the highest prognostic power. ASB2, PRPH, and GPR15/TCL1A were predicted to function by interacting with CASQ2/PDK4/EPHA67, PTN, and CXCL12, respectively. TCL1A and GPR15 influenced the infiltration levels of B cells and dendritic cells, while the expression of PRPH was positively associated with the abundance of macrophages. HPA analysis supported the downregulation of PRPH, RNASE7, CASQ2, EPHA6, and PDK4 in RC compared with normal controls.\nCONCLUSION: Our immune-related signature panel may be a promising prognostic indicator for RC.", "claims": [{"id": "claim-method", "statement": "The associations between the expression of selected prognostic genes and the abundance of six tumor-infiltrating immune cells in TCGA-PRAD (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells) were estimated from the Tumor Immune Estimation Resource (TIMER; https://cistrome.shinyapps.io/timer/) based on Spearman's correlation test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33833937", "locator": "sections[8] \"2.6. Analysis of Immune Cell Infiltration\" paragraph 2", "quote": "The associations between the expression of selected prognostic genes and the abundance of six tumor-infiltrating immune cells in TCGA-PRAD (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells) were estimated from the Tumor Immune Estimation Resource (TIMER; https://cistrome.shinyapps.io/timer/) based on Spearman's correlation test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated for this study can be found in GEO (http://www.ncbi.nlm.nih.gov/geo/; GSE123390, GSE56699) and TCGA (https://gdc-portal.nci.nih.gov/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33833937", "locator": "sections[20] \"Data Availability\" paragraph 2", "quote": "The datasets generated for this study can be found in GEO (http://www.ncbi.nlm.nih.gov/geo/; GSE123390, GSE56699) and TCGA (https://gdc-portal.nci.nih.gov/)."}], "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:33833937"], "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:GSE123390"], "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:GSE123390"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33833937", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2021/6697407", "sha256": "sha256:d51ba826dbc64805fce1f2b1b5d4568ad236925b719609d4920c2f8ef469a6c1", "bytes": 49723, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2021/6697407", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8012151", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE123390", "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=GSE123390", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE123390", "version": null, "note": "The datasets generated for this study can be found in GEO (http://www.ncbi.nlm.nih.gov/geo/; GSE123390, GSE56699) and TCGA (https://gdc-portal.nci.nih.gov/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated for this study can be found in GEO (http://www.ncbi.nlm.nih.gov/geo/; GSE123390, GSE56699) and TCGA (https://gdc-portal.nci.nih.gov/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3502511", "GSM3502512", "GSM3502513", "GSM3502514", "GSM3502515", "GSM3502516", "GSM3502517", "GSM3502518", "GSM3502519", "GSM3502520", "GSM3502521", "GSM3502522", "GSM3502523", "GSM3502524", "GSM3502525", "GSM3502526", "GSM3502527", "GSM3502528", "GSM3502529", "GSM3502530", "GSM3502531", "GSM3502532", "GSM3502533", "GSM3502534", "GSM3502535", "GSM3502536", "GSM3502537", "GSM3502538", "GSM3502539", "GSM3502540", "GSM3502541", "GSM3502542", "GSM3502543"], "sample_count": 33, "group_sizes": null, "group_sizes_basis": null, "platform": "17586", "taxon": "Homo sapiens", "title": "Locally advanced rectal cancer transcriptomic-based secretome analysis according to neoadjuvant chemoradiotherapy response", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE56699", "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=GSE56699", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE56699", "version": null, "note": "The datasets generated for this study can be found in GEO (http://www.ncbi.nlm.nih.gov/geo/; GSE123390, GSE56699) and TCGA (https://gdc-portal.nci.nih.gov/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated for this study can be found in GEO (http://www.ncbi.nlm.nih.gov/geo/; GSE123390, GSE56699) and TCGA (https://gdc-portal.nci.nih.gov/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1366951", "GSM1366952", "GSM1366953", "GSM1366954", "GSM1366955", "GSM1366956", "GSM1366957", "GSM1366958", "GSM1366959", "GSM1366960", "GSM1366961", "GSM1366962", "GSM1366963", "GSM1366964", "GSM1366965", "GSM1366966", "GSM1366967", "GSM1366968", "GSM1366969", "GSM1366970", "GSM1366971", "GSM1366972", "GSM1366973", "GSM1366974", "GSM1366975", "GSM1366976", "GSM1366977", "GSM1366978", "GSM1366979", "GSM1366980", "GSM1366981", "GSM1366982", "GSM1366983", "GSM1366984", "GSM1366985", "GSM1366986", "GSM1366987", "GSM1366988", "GSM1366989", "GSM1366990", "GSM1366991", "GSM1366992", "GSM1366993", "GSM1366994", "GSM1366995", "GSM1366996", "GSM1366997", "GSM1366998", "GSM1366999", "GSM1367000", "GSM1367001", "GSM1367002", "GSM1367003", "GSM1367004", "GSM1367005", "GSM1367006", "GSM1367007", "GSM1367008", "GSM1367009", "GSM1367010", "GSM1367011", "GSM1367012", "GSM1367013", "GSM1367014", "GSM1367015", "GSM1367016", "GSM1367017", "GSM1367018", "GSM1367019", "GSM1367020", "GSM1367021", "GSM1367022"], "sample_count": 72, "group_sizes": null, "group_sizes_basis": null, "platform": "14951", "taxon": "Homo sapiens", "title": "Stromal contribution to expression signatures of colorectal cancer (rectal samples)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33833937:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:689b2b1ab546b895b856a2e359fb527eb8ee961d67e985a6b73ec0840f2868b9", "bytes": 1159, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#tab1", "version": null, "note": "Preserved modules identified based on weighted gene coexpression network analysis.", "structure": {"pmcid": "PMC8012151", "section_index": 12, "section_title": "3.2. Identification of RC-Related Modules by WGCNA", "row_count": 11, "column_count": 8}, "table": {"label": "Table 1", "caption": "Preserved modules identified based on weighted gene coexpression network analysis.", "rows": [["ID", "Color", "Module size", "Preservation infor", "#DEGs", "Enrichment infor"], ["Z-score", "p value", "Enrichment fold (95% CI)", "p hyper"], ["Module 1", "Black", "99", "13.9321", "5.30e − 11", "—", "—", "—"], ["Module 2", "Blue", "683", "13.2267", "1.40e − 30", "—", "—", "—"], ["Module 3", "Brown", "244", "8.3117", "4.50e − 19", "34", "2.838 (1.879-4.181)", "1.38e − 06"], ["Module 4", "Green", "226", "0.9366", "4.90e − 04", "5", "0.383 (0.122-0.918)", "2.42e − 02"], ["Module 5", "Grey", "2545", "8.1319", "6.60e − 32", "146", "1.169 (0.940-1.448)", "1.55e − 01"], ["Module 6", "Pink", "86", "1.0653", "1.60e − 02", "5", "1.184 (0.371-2.911)", "6.17e − 01"], ["Module 7", "Red", "123", "10.5572", "8.80e − 09", "3", "0.497 (0.100-1.504)", "2.86e − 01"], ["Module 8", "Turquoise", "796", "8.3751", "9.20e − 14", "11", "0.291 (0.143-0.533)", "3.75e − 06"], ["Module 9", "Yellow", "230", "12.5199", "7.10e − 07", "43", "3.807 (2.617-5.440)", "2.63e − 11"]], "row_count": 11, "column_count": 8, "numeric_cells": 58, "header_rows": 2, "locator": "section[12]/table-wrap[1]#tab1"}}, {"id": "asset:table:pmid:33833937:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8044b92d0bcf81b12c0349c9a731487452259876bb31d56aa2d69e9876f5a65d", "bytes": 975, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[14]/table-wrap[1]#tab2", "version": null, "note": "The optimal signature for prognosis prediction.", "structure": {"pmcid": "PMC8012151", "section_index": 14, "section_title": "3.4. 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Development of a Prognostic Risk Score", "row_count": 14, "column_count": 8}, "table": {"label": "Table 3", "caption": "Univariate and multivariate Cox regression of the clinical features and risk score.", "rows": [["Clinical characteristics", "TCGA (N = 152)", "Univariate Cox", "Multivariate Cox"], ["HR", "95% CI", "p value", "HR", "95% CI", "p value"], ["Age (years, mean ± SD)", "64.16 ± 11.96", "1.100", "1.049-1.154", "3.40e − 05", "1.112", "1.056-1.170", "6.08e − 05"], ["Gender (female/male)", "72/80", "0.762", "0.321-1.807", "5.36e − 01", "—", "—", "—"], ["Pathologic M (M0/M1/-)", "119/21/12", "3.081", "1.158-8.196", "1.77e − 02", "8.911", "1.065-14.591", "4.36e − 02"], ["Pathologic N (N0/N1/N2/-)", "80/41/30/1", "1.920", "1.166-3.160", "7.48e − 03", "6.169", "1.956-19.457", "1.91e − 03"], ["Pathologic T (T1/T2/T3/T4)", "9/26/104/13", "2.147", "0.932-4.947", "7.63e − 02", "1.460", "0.563-3.789", "4.37e − 01"], ["Pathologic stage (I/II/III/IV/-)", "28/49/47/22/6", "1.976", "1.206-3.238", "5.36e − 03", "1.197", "1.041-1.946", "4.24e − 02"], ["Colon polyps present (yes/no/-)", "10/57/85", "1.006", "0.205-4.931", "9.95e − 01", "—", "—", "—"], ["History of colon polyps (yes/no/-)", "30/104/18", "1.125", "0.364-3.48", "8.38e − 01", "—", "—", "—"], ["Recurrence (yes/no/-)", "6/36/110", "2.828", "0.145-55.14", "4.80e − 01", "—", "—", "—"], ["Lymphatic invasion (yes/no/-)", "61/75/16", "0.885", "0.327-2.399", "8.10e − 01", "—", "—", "—"], ["Radiotherapy (yes/no/-)", "18/99/35", "0.345", "0.260-1.094", "7.52e − 02", "—", "—", "—"], ["Risk score model status (high/low)", "76/76", "5.001", "1.681-14.88", "9.73e − 04", "5.462", "1.371-21.754", "1.61e − 02"]], "row_count": 14, "column_count": 8, "numeric_cells": 69, "header_rows": 2, "locator": "section[14]/table-wrap[2]#tab3"}}], "gaps": ["asset:data:geo:GSE123390 not downloaded", "asset:data:geo:GSE123390 licence not read", "asset:data:geo:GSE56699 not downloaded", "asset:data:geo:GSE56699 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The associations between the expression of selected prognostic genes and the abundance of six tumor-infiltrating immune cells in TCGA-PRAD (B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells) were estimated from the Tumor Immune Estimation Resource (TIMER; 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