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pmid:35155447

Positive Correlation Between LTA Expression and Overall Immune Activity Suggests an Increased Probability of Survival in Uterine Corpus Endometrial Carcinoma.

Mingjie Shi · Fei Luo · Taotao Shao · Hengli Zhang · Taili Yang · Yue Wei · Riling Chen · Runmin Guo

Frontiers in cell and developmental biology · 2021 doi:10.3389/fcell.2021.793793

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Experiment

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Data

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Analysis

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title
Positive Correlation Between LTA Expression and Overall Immune Activity Suggests an Increased Probability of Survival in Uterine Corpus Endometrial Carcinoma.
doi
10.3389/fcell.2021.793793
pmid
35155447
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Mingjie Shi
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Fei Luo
[2]
Taotao Shao
[3]
Hengli Zhang
[4]
Taili Yang
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Yue Wei
[6]
Riling Chen
[7]
Runmin Guo
journal
Frontiers in cell and developmental biology
year
2021
abstract
Mounting evidence indicates that immune status plays a crucial role in tumor progress and metastasis, while there are no effective and easily assayed biomarkers to reflect it in uterine corpus endometrial carcinoma (UCEC) patients. Here, we attempted to identify the potential biomarkers that were differentially expressed between normal and tumor tissues and involved in prognosis and immune microenvironment of UCEC patients. RNA-seq data with relevant clinical information were obtained from The Cancer Genome Atlas (TCGA). ssGSEA algorithm was applied to calculate the enrichment scores of every tumor infiltration lymphocyte (TIL) set in each sample, and patients were then divided into three clusters using multiple R packages. Cox analysis, ESTIMATE, and CIBERSORT were utilized to determine the differentially expressed immune-related genes (DEIGs) with overall survival, and to explore their roles in prognosis, immune microenvironment, and immunotherapeutic response. The TIMER and TISIDB databases were utilized to predict the effectiveness of immunotherapy in UCEC patients. LTA was finally identified to be significantly upregulated in tumor tissues and closely associated with prognosis and immunological status, which was then verified in GSE17025. In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22-0.80) (p = 0.008). Patients with high LTA expression had better survival and apparently immune-activated phenotypes, such as more tumor mutation burden (TMB), stronger immune cell infiltrations, higher expression of immunosuppressive points, and higher immunophenoscore, meaning they had an immunotherapeutic advantage over those with low LTA expression. TIMER and TISIDB indicated that LTA was highly expressed in UCEC, and its expression was negatively correlated with stages and positively related to prognosis. Additionally, we found that LTA ectopic expression weakened the proliferation ability of RL95-2 cells. All these findings indicated that LTA could act as a novel and easily assayed biomarker to predict immunological status and clinical outcomes and even as an antioncogene to explore UCEC in depth.
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Publicly available datasets were analyzed in this study. These data can be found here: Publicly available datasets TCGA (https://portal.gdc.cancer.gov/), GSE17025 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), TIMER (http://timer.comp-genomics.org/), and TISIDB (http://cis.hku.hk/TISIDB/) were analyzed in this study.
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Publicly available datasets were analyzed in this study. These data can be found here: Publicly available datasets TCGA (https://portal.gdc.cancer.gov/), GSE17025 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), TIMER (http://timer.comp-genomics.org/), and TISIDB (http://cis.hku.hk/TISIDB/) were analyzed in this study.
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In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22–0.80) (p = 0.008).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35155447", "kind": "science-record", "revision": 4, "content_hash": "sha256:596426264df3b790bca32c54d5f09752fb0027ba0548da82044ed0f2ca0450b5", "created_at": "2026-11-01T17:36:54Z", "updated_at": "2026-11-01T22:05:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Positive Correlation Between LTA Expression and Overall Immune Activity Suggests an Increased Probability of Survival in Uterine Corpus Endometrial Carcinoma.", "doi": "10.3389/fcell.2021.793793", "pmid": "35155447", "authors": ["Mingjie Shi", "Fei Luo", "Taotao Shao", "Hengli Zhang", "Taili Yang", "Yue Wei", "Riling Chen", "Runmin Guo"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Mounting evidence indicates that immune status plays a crucial role in tumor progress and metastasis, while there are no effective and easily assayed biomarkers to reflect it in uterine corpus endometrial carcinoma (UCEC) patients. Here, we attempted to identify the potential biomarkers that were differentially expressed between normal and tumor tissues and involved in prognosis and immune microenvironment of UCEC patients. RNA-seq data with relevant clinical information were obtained from The Cancer Genome Atlas (TCGA). ssGSEA algorithm was applied to calculate the enrichment scores of every tumor infiltration lymphocyte (TIL) set in each sample, and patients were then divided into three clusters using multiple R packages. Cox analysis, ESTIMATE, and CIBERSORT were utilized to determine the differentially expressed immune-related genes (DEIGs) with overall survival, and to explore their roles in prognosis, immune microenvironment, and immunotherapeutic response. The TIMER and TISIDB databases were utilized to predict the effectiveness of immunotherapy in UCEC patients. LTA was finally identified to be significantly upregulated in tumor tissues and closely associated with prognosis and immunological status, which was then verified in GSE17025. In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22-0.80) (p = 0.008). Patients with high LTA expression had better survival and apparently immune-activated phenotypes, such as more tumor mutation burden (TMB), stronger immune cell infiltrations, higher expression of immunosuppressive points, and higher immunophenoscore, meaning they had an immunotherapeutic advantage over those with low LTA expression. TIMER and TISIDB indicated that LTA was highly expressed in UCEC, and its expression was negatively correlated with stages and positively related to prognosis. Additionally, we found that LTA ectopic expression weakened the proliferation ability of RL95-2 cells. All these findings indicated that LTA could act as a novel and easily assayed biomarker to predict immunological status and clinical outcomes and even as an antioncogene to explore UCEC in depth.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate Cox proportional hazards regression analyses were carried out to identify those DEIGs associated with the prognosis of UCEC patients.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35155447", "locator": "sections[7] \"Exploration of Signatures Associated With Prognosis\" paragraph 2", "quote": "Univariate and multivariate Cox proportional hazards regression analyses were carried out to identify those DEIGs associated with the prognosis of UCEC patients."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found here: Publicly available datasets TCGA (https://portal.gdc.cancer.gov/), GSE17025 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), TIMER (http://timer.comp-genomics.org/), and TISIDB (http://cis.hku.hk/TISIDB/) were analyzed in this study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35155447", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. These data can be found here: Publicly available datasets TCGA (https://portal.gdc.cancer.gov/), GSE17025 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), TIMER (http://timer.comp-genomics.org/), and TISIDB (http://cis.hku.hk/TISIDB/) were analyzed in this study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22–0.80) (p = 0.008).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22–0.80) (p = 0.008)."}, "evidence": [{"asset": "source:pmid:35155447", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22–0.80) (p = 0.008)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In multivariate analysis, the hazard ratio of LTA was 0.42 with 95% CI (0.22–0.80) (p = 0.008).", "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:35155447"], "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:GSE17025"], "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:GSE17025"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35155447", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.793793", "sha256": "sha256:9169bc68a8b2c4db9095ff6b9eca31eb56bf92f9a610e61155ba145c0c59ec97", "bytes": 46775, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcell.2021.793793", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8832144", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE17025", "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=GSE17025", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE17025", "version": null, "note": "Publicly available datasets were analyzed in this study. These data can be found here: Publicly available datasets TCGA (https://portal.gdc.cancer.gov/), GSE17025 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), TIMER (http://timer.comp-genomics.org/), and TISIDB (http://cis.hku.hk/TISIDB/) were analyzed in this study.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. These data can be found here: Publicly available datasets TCGA (https://portal.gdc.cancer.gov/), GSE17025 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi), TIMER (http://timer.comp-genomics.org/), and TISIDB (http://cis.hku.hk/TISIDB/) were analyzed in this study.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM425837", "GSM425838", "GSM425839", "GSM425840", "GSM425841", "GSM425842", "GSM425843", "GSM425844", "GSM425845", "GSM425846", "GSM425847", "GSM425848", "GSM425849", "GSM425850", "GSM425851", "GSM425852", "GSM425853", "GSM425854", "GSM425855", "GSM425856", "GSM425857", "GSM425858", "GSM425859", "GSM425860", "GSM425861", "GSM425862", "GSM425863", "GSM425864", "GSM425865", "GSM425866", "GSM425867", "GSM425868", "GSM425869", "GSM425870", "GSM425871", "GSM425872", "GSM425873", "GSM425874", "GSM425875", "GSM425876", "GSM425877", "GSM425878", "GSM425879", "GSM425880", "GSM425881", "GSM425882", "GSM425883", "GSM425884", "GSM425885", "GSM425886", "GSM425887", "GSM425888", "GSM425889", "GSM425890", "GSM425891", "GSM425892", "GSM425893", "GSM425894", "GSM425895", "GSM425896", "GSM425897", "GSM425898", "GSM425899", "GSM425900", "GSM425901", "GSM425902", "GSM425903", "GSM425904", "GSM425905", "GSM425906", "GSM425907", "GSM425908", "GSM425909", "GSM425910", "GSM425911", "GSM425912", "GSM425913", "GSM425914", "GSM425915", "GSM425916", "GSM425917", "GSM425918", "GSM425919", "GSM425920", "GSM425921", "GSM425922", "GSM425923", "GSM425924", "GSM425925", "GSM425926", "GSM425927", "GSM425928", "GSM425929", "GSM425930", "GSM425931", "GSM425932", "GSM425933", "GSM425934", "GSM425935", "GSM425936", "GSM425937", "GSM425938", "GSM425939"], "sample_count": 103, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene Expression Analysis of Stage I Endometrial Cancers", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE17025 not downloaded", "asset:data:geo:GSE17025 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Univariate and multivariate Cox proportional hazards regression analyses were carried out to identify those DEIGs associated with the prognosis of UCEC patients."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}, {"id": "method-4", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.8, "band": "high", "quote": "Limma"}}, {"id": "method-5", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "classification_metrics", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}, {"id": "target-published-estimate-p-value", "claim_id": "claim-target-result", "operation": "classification_metrics", "expected_value": 0.008, "unit": "p-value", "tolerance": null, "state": "complete", "note": "The threshold the paper applied to its own result, as the paper states it. 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