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pmid:34581419

BCG immunotherapy inhibits cancer progression by promoting the M1 macrophage differentiation of THP‑1 cells via the Rb/E2F1 pathway in cervical carcinoma.

Limin Liu · Wenjuan Shi · Xiao Xiao · Xuemei Wu · Haiyan Hu · Shixin Yuan · Kai Liu · Zhihua Liu

Oncology reports · 2021 doi:10.3892/or.2021.8196

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:34581419
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science-record
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https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T15:41:54Z
updated_at
2026-11-01T22:47:37Z
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paper object · 10 fields
state
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title
BCG immunotherapy inhibits cancer progression by promoting the M1 macrophage differentiation of THP‑1 cells via the Rb/E2F1 pathway in cervical carcinoma.
doi
10.3892/or.2021.8196
pmid
34581419
authors array · 8 items
[0]
Limin Liu
[1]
Wenjuan Shi
[2]
Xiao Xiao
[3]
Xuemei Wu
[4]
Haiyan Hu
[5]
Shixin Yuan
[6]
Kai Liu
[7]
Zhihua Liu
journal
Oncology reports
year
2021
abstract
Bacillus Calmette‑Guérin (BCG) immunotherapy increases macrophage polarization toward M1‑type macrophages. In the present study, to identify the M1/M2 marker genes in the carcinogenesis and progression of cervical cancer, the microarray datasets GSE9750 and GSE7803 were downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena browser. Survival analysis revealed that M1 markers (IL‑12) were involved in anti‑tumour progression, and M2 markers (IL‑10) were involved in the carcinogenesis and invasion of cervical cancer. The expression of M1 markers (IL‑12, inducible nitric oxide synthase and CD80) and M2 markers (IL‑10 and arginase) was examined to determine whether BCG affects the polarization of macrophages and to elucidate the underlying mechanisms. The results revealed that BCG promoted macrophage polarization towards the M1 phenotype and enhanced the transition of M2 to M1 macrophages. The results also revealed that polarized M1 macrophages induced by BCG decreased the protein expression of phosphorylated (p‑)retinoblastoma (Rb)/E2F transcription factor 1 (E2F1), inhibited the proliferation and promoted the apoptosis of HeLa cells. On the whole, these results demonstrated that BCG promoted the anti‑tumour progression of M1 macrophages and inhibited the pro‑tumour activation of M2 macrophages via the Rb/E2F1 signalling pathway in HeLa cells. This suggests the possibility of a direct translation of this combination strategy to clinical practice for the treatment of cervical cancer.
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The association between mRNA expression and overall survival (OS), or disease-free survival (DFS) was determined using the ‘Cox PH Model’ with the Kaplan-Meier survival plot. The survival curves of samples with high and low gene expression were compared using the log-rank test.
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sections[5] "Survival analysis" paragraph 2
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The association between mRNA expression and overall survival (OS), or disease-free survival (DFS) was determined using the ‘Cox PH Model’ with the Kaplan-Meier survival plot. The survival curves of samples with high and low gene expression were compared using the log-rank test.
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The microarray datasets, GSE9750 and GSE7803 (Affymetrix GPL96 platform, Affymetrix Human Genome U133A Array), and TCGA-cervical squamous cell carcinoma (CESC) were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) and UCSC Xena browser (https://xenabrowser.net/datapages/). The GSE9750 dataset contains 24 normal cervical tissue samples and 28 cervical cancer tissue samples.
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sections[4] "Cervical cancer datasets and pre-processing" paragraph 2
quote
The microarray datasets, GSE9750 and GSE7803 (Affymetrix GPL96 platform, Affymetrix Human Genome U133A Array), and TCGA-cervical squamous cell carcinoma (CESC) were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) and UCSC Xena browser (https://xenabrowser.net/datapages/). The GSE9750 dataset contains 24 normal cervical tissue samples and 28 cervical cancer tissue samples.
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The microarray datasets, GSE9750 and GSE7803 (Affymetrix GPL96 platform, Affymetrix Human Genome U133A Array), and TCGA-cervical squamous cell carcinoma (CESC) were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) and UCSC Xena browser (https://xenabrowser.net/datapages/). The GSE9750 dataset contains 24 normal cervical tissue samples and 28 cervical cancer tissue samples.
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Human pre-invasive and invasive cervical squamous cell carcinomas and normal cervical epithelia
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The microarray datasets, GSE9750 and GSE7803 (Affymetrix GPL96 platform, Affymetrix Human Genome U133A Array), and TCGA-cervical squamous cell carcinoma (CESC) were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) and UCSC Xena browser (https://xenabrowser.net/datapages/). The GSE9750 dataset contains 24 normal cervical tissue samples and 28 cervical cancer tissue samples.
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The microarray datasets, GSE9750 and GSE7803 (Affymetrix GPL96 platform, Affymetrix Human Genome U133A Array), and TCGA-cervical squamous cell carcinoma (CESC) were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) and UCSC Xena browser (https://xenabrowser.net/datapages/). The GSE9750 dataset contains 24 normal cervical tissue samples and 28 cervical cancer tissue samples.
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Identification of gene expression profiles in cervical cancer
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Primer sequences used for RT-qPCR.
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Reverse transcription-quantitative PCR (RT-qPCR)
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Table I.
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Primer sequences used for RT-qPCR.
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IL-10
[1]
Forward primer: CACTGCTCTGTTGCCTGGTC
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[0]
[1]
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Forward primer: GGACCTTGGACCAGAGCAGT
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[0]
[1]
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[0]
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[0]
[1]
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[0]
iNOS
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Forward primer: GAGCCAGGCCACCTCTATGT
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[0]
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Reverse primer: GTCCTCGACCTGCTCCTCAT
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[0]
GAPDH
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Forward primer: CGGAGTCAACGGATTTGGTCGTAT
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[0]
[1]
Reverse primer: AGCCTTCTCCATGGTGGTGAAGAC
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GO and KEGG pathway enrichment analysis of DEGs in GSE 7803/9750 CESC samples.
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Identification, KEGG and GO enrichment analyses of DEGs in GSE7803/9750
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Table II.
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GO and KEGG pathway enrichment analysis of DEGs in GSE 7803/9750 CESC samples.
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The association between mRNA expression and overall survival (OS), or disease-free survival (DFS) was determined using the ‘Cox PH Model’ with the Kaplan-Meier survival plot. The survival curves of samples with high and low gene expression were compared using the log-rank test.
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The microarray datasets, GSE9750 and GSE7803 (Affymetrix GPL96 platform, Affymetrix Human Genome U133A Array), and TCGA-cervical squamous cell carcinoma (CESC) were downloaded from the GEO database (http://www.ncbi.nlm.nih.gov/geo) and UCSC Xena browser (https://xenabrowser.net/datapages/). The GSE9750 dataset contains 24 normal cervical tissue samples and 28 cervical cancer tissue samples.
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esis and progression of cervical cancer, the microarray datasets GSE9750 and GSE7803 were downloaded
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inhibited the proliferation and promoted the apoptosis of HeLa cells. On the whole, these results d
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proliferation and promoted the apoptosis of HeLa cells. On the whole, these results demonstra
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The association between mRNA expression and overall survival (OS), or disease-free survival (DFS) was determined using the ‘Cox PH Model’ with the Kaplan-Meier survival plot. The survival curves of samples with high and low gene expression were compared using the log-rank test.
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Complete file
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In the present study, to identify the M1/M2 marker genes in the carcinogenesis and progression of cervical cancer, the microarray datasets GSE9750 and GSE7803 were downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and the University of California Santa Cruz (UCSC) Xena browser. Survival analysis revealed that M1 markers (IL‑12) were involved in anti‑tumour progression, and M2 markers (IL‑10) were involved in the carcinogenesis and invasion of cervical cancer. The expression of M1 markers (IL‑12, inducible nitric oxide synthase and CD80) and M2 markers (IL‑10 and arginase) was examined to determine whether BCG affects the polarization of macrophages and to elucidate the underlying mechanisms. The results revealed that BCG promoted macrophage polarization towards the M1 phenotype and enhanced the transition of M2 to M1 macrophages. The results also revealed that polarized M1 macrophages induced by BCG decreased the protein expression of phosphorylated (p‑)retinoblastoma (Rb)/E2F transcription factor 1 (E2F1), inhibited the proliferation and promoted the apoptosis of HeLa cells. On the whole, these results demonstrated that BCG promoted the anti‑tumour progression of M1 macrophages and inhibited the pro‑tumour activation of M2 macrophages via the Rb/E2F1 signalling pathway in HeLa cells. This suggests the possibility of a direct translation of this combination strategy to clinical practice for the treatment of cervical cancer.", "claims": [{"id": "claim-method", "statement": "The association between mRNA expression and overall survival (OS), or disease-free survival (DFS) was determined using the ‘Cox PH Model’ with the Kaplan-Meier survival plot. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:34581419", "data:geo:GSE7803", "asset:table:pmid:34581419:1", "asset:table:pmid:34581419:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE7803"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:50:40Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 28887, "completion_tokens": 2087, "cached_tokens": 520}}, "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:34581419", "type": "paper", "label": "pmid:34581419"}, {"id": "source:pmid:34581419", "type": "manuscript", "label": "PMID 34581419 full text"}, {"id": "data:geo:GSE7803", "type": "dataset", "label": "GEO GSE7803"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34581419", "type": "paper", "label": "pmid:34581419"}, {"id": "source:pmid:34581419", "type": "manuscript", "label": "PMID 34581419 full text"}, {"id": "data:geo:GSE7803", "type": "dataset", "label": "GEO GSE7803"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34581419", "type": "extraction", "used": ["source:pmid:34581419"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE7803", "type": "accession_resolution", "used": ["data:geo:GSE7803"], "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:34581419", "parent_hash": "sha256:5c1877a9e4fd17ac9e253ee79cfaef83678e6724adb5b93af4aa5fef91f38041", "fork_of": null, "generation": 8}, "gaps": ["asset:data:geo:GSE7803 licence not read", "asset:data:geo:GSE7803 not downloaded", "asset:data:geo:GSE9750 licence not read", "asset:data:geo:GSE9750 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["esis and progression of cervical cancer, the microarray datasets GSE9750 and GSE7803 were downloaded"], "order_basis": "paper_text_order:336", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["inhibited the proliferation and promoted the apoptosis of HeLa cells. On the whole, these results d"], "order_basis": "paper_text_order:1313", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["proliferation and promoted the apoptosis of HeLa cells. On the whole, these results demonstra", "phages via the Rb/E2F1 signalling pathway in HeLa cells. This suggests the possibility of a di", "humidified incubator with 5% CO2. 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