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pmid:35223862

Functions of RNF Family in the Tumor Microenvironment and Drugs Prediction in Grade II/III Gliomas.

Jingwei Zhang · Zeyu Wang · Hao Zhang · Ziyu Dai · Xisong Liang · Shuwang Li · Xun Zhang · Fangkun Liu · Zhixiong Liu · Kui Yang · Quan Cheng

Frontiers in cell and developmental biology · 2021 doi:10.3389/fcell.2021.754873

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title
Functions of RNF Family in the Tumor Microenvironment and Drugs Prediction in Grade II/III Gliomas.
doi
10.3389/fcell.2021.754873
pmid
35223862
authors array · 11 items
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Jingwei Zhang
[1]
Zeyu Wang
[2]
Hao Zhang
[3]
Ziyu Dai
[4]
Xisong Liang
[5]
Shuwang Li
[6]
Xun Zhang
[7]
Fangkun Liu
[8]
Zhixiong Liu
[9]
Kui Yang
[10]
Quan Cheng
journal
Frontiers in cell and developmental biology
year
2021
abstract
Increasing evidence has demonstrated that RING finger (RNF) proteins played a vital role in cellular and physiological processes and various diseases. However, the function of RNF proteins in low-grade glioma (LGG) remains unknown. In this study, 138 RNF family members revealed their role in LGG. The TCGA database was used as the training cohort; two CGGA databases and GSE108474 were selected as external validation cohorts. Patients were grouped into cluster 1 and cluster 2, both in the training and validation cohorts, using consensus clustering analysis. The prognosis of patients in cluster 1 is significantly better than that in cluster 2. Meanwhile, biofunction prediction was further introduced to explore the potential mechanisms that led to differences in survival outcomes. Patients in Cluster 2 showed more complicated immunocytes infiltration and highly immunosuppressive features than cluster 1. Enrichment pathways such as negative regulation of mast cell activation, DNA replication, mismatch repair, Th17 cell differentiation, antigen processing and presentation, dendritic cell antigen processing and presentation, dendritic cell differentiation were also enriched in cluster 2 patients. For the last, the main contributors were distinguished by employing a machine learning algorithm. A lot of targeted and small molecule drugs that are sensitive to patients in cluster 2 were predicted. Importantly, we discovered TRIM8, DTX2, and TRAF5 as the most vital contributors from the RNF family, which were related to immune infiltration in LGG tumor immune landscape. In this study, we demonstrated the predicted role of RNF proteins in LGG. In addition, we found out three markers among RNF proteins that are closely related to the immune aspects of LGG, which might serve as novel therapeutic targets for immunotherapy in the future.
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Kaplan-Meier analysis in the TCGA database between two clusters showed that patients in cluster 1 had a better prognosis than cluster 2 during the overall survival time (p < 0.0001; Figure 2C).
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Kaplan-Meier analysis in the TCGA database between two clusters showed that patients in cluster 1 had a better prognosis than cluster 2 during the overall survival time (p < 0.0001; Figure 2C).
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sections[11] "Clustering Model Based on RNF Genes Identified Two Clusters with Distinct Outcomes and Clinicopathological Features" paragraph 2
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Kaplan-Meier analysis in the TCGA database between two clusters showed that patients in cluster 1 had a better prognosis than cluster 2 during the overall survival time (p < 0.0001; Figure 2C).
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Kaplan-Meier analysis in the TCGA database between two clusters showed that patients in cluster 1 had a better prognosis than cluster 2 during the overall survival time (p < 0.0001; Figure 2C).
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GSM2899652
[475]
GSM2899653
[476]
GSM2899654
[477]
GSM2899655
[478]
GSM2899656
[479]
GSM2899657
[480]
GSM2899658
[481]
GSM2899659
[482]
GSM2899660
[483]
GSM2899661
[484]
GSM2899662
[485]
GSM2899663
[486]
GSM2899664
[487]
GSM2899665
[488]
GSM2899666
[489]
GSM2899667
[490]
GSM2899668
[491]
GSM2899669
[492]
GSM2899670
[493]
GSM2899671
[494]
GSM2899672
[495]
GSM2899673
[496]
GSM2899674
[497]
GSM2899675
[498]
GSM2899676
[499]
GSM2899677
[500]
GSM2899678
[501]
GSM2899679
[502]
GSM2899680
[503]
GSM2899681
[504]
GSM2899682
[505]
GSM2899683
[506]
GSM2899684
[507]
GSM2899685
[508]
GSM2899686
[509]
GSM2899687
[510]
GSM2899688
[511]
GSM2899689
[512]
GSM2899690
[513]
GSM2899691
[514]
GSM2899692
[515]
GSM2899693
[516]
GSM2899694
[517]
GSM2899695
[518]
GSM2899696
[519]
GSM2899697
[520]
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[521]
GSM2899699
[522]
GSM2899700
[523]
GSM2899701
[524]
GSM2899702
[525]
GSM2899703
[526]
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[527]
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[528]
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[529]
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[530]
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[531]
GSM2899709
[532]
GSM2899710
[533]
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[534]
GSM2899712
[535]
GSM2899713
[536]
GSM2899714
[537]
GSM2899715
[538]
GSM2899716
[539]
GSM2899717
[540]
GSM2899718
[541]
GSM2899719
[542]
GSM2899720
[543]
GSM2899721
[544]
GSM2899722
[545]
GSM2899723
[546]
GSM2899724
[547]
GSM2899725
[548]
GSM2899726
[549]
GSM2899727
sample_count
550
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
The REMBRANDT study – a large collection of genomic data from brain cancer patients [gene expression]
resolution_checked_at
2026-11-01T17:30:42Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 2 items
[0]
asset:data:geo:GSE108474 not downloaded
[1]
asset:data:geo:GSE108474 licence not read
analysis object · 4 fields
state
complete
methods array · 4 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
1
band
verbatim
quote
The Kaplan-Meier analysis was applied to analyze the survival prognosis between two groups, and log-rank was used for examination.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[0]
logrank_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
log-rank
[2] object · 10 fields
id
method-3
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.8
band
high
quote
GO enrichment
[3] object · 10 fields
id
method-4
family
diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
[1]
roc_curve
[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.8
band
high
quote
ROC curve
targets array · 1 item
[0] object · 8 fields
id
target-published-estimate
claim_id
claim-target-result
operation
classification_metrics
unit
p-value
tolerance
null
state
complete
note
The threshold the paper applied to its own result, as the paper states it. A run that reproduces the effect is judged against this threshold.
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
survival_km
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 1 item
[0]
GSE108474
resolved_accessions array · 1 item
[0]
GSE108474
statements array · 1 item
[0]
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.
basis
The paper names GSE108474 in Rembrandt datasets and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
survival_km
assets array · 2 items
[0]
source:pmid:35223862
[1]
data:geo:GSE108474
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE108474
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T17:36:10Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
16057
completion_tokens
2168
cached_tokens
128
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:35223862
type
paper
label
pmid:35223862
[1] object · 3 fields
id
source:pmid:35223862
type
manuscript
label
PMID 35223862 full text
[2] object · 3 fields
id
data:geo:GSE108474
type
dataset
label
GEO GSE108474
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:35223862
type
paper
label
pmid:35223862
[1] object · 3 fields
id
source:pmid:35223862
type
manuscript
label
PMID 35223862 full text
[2] object · 3 fields
id
data:geo:GSE108474
type
dataset
label
GEO GSE108474
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-35223862
type
extraction
used array · 1 item
[0]
source:pmid:35223862
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE108474
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE108474
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
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 object · 4 fields
parent_id
pmid:35223862
parent_hash
sha256:a5615650627a786cb1bcbc416efaaceb22afa81550558b0e1efd1530ceed7bc9
fork_of
null
gaps array · 6 items
[0]
asset:data:geo:GSE108474 licence not read
[1]
asset:data:geo:GSE108474 not downloaded
[2]
execution.not_run
[3]
review.human_critique
[4]
review.independent_reader
[5]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
survival_km
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
The Kaplan-Meier analysis was applied to analyze the survival prognosis between two groups, and log-rank was used for examination.
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35223862", "kind": "science-record", "revision": 5, "content_hash": "sha256:a6d5bb505dfb9564faa50d27ae7a290b3fe906b230744b04012101d61340259a", "created_at": "2026-11-01T17:36:59Z", "updated_at": "2026-11-01T22:48:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Functions of RNF Family in the Tumor Microenvironment and Drugs Prediction in Grade II/III Gliomas.", "doi": "10.3389/fcell.2021.754873", "pmid": "35223862", "authors": ["Jingwei Zhang", "Zeyu Wang", "Hao Zhang", "Ziyu Dai", "Xisong Liang", "Shuwang Li", "Xun Zhang", "Fangkun Liu", "Zhixiong Liu", "Kui Yang", "Quan Cheng"], "journal": "Frontiers in cell and developmental biology", "year": 2021, "abstract": "Increasing evidence has demonstrated that RING finger (RNF) proteins played a vital role in cellular and physiological processes and various diseases. However, the function of RNF proteins in low-grade glioma (LGG) remains unknown. In this study, 138 RNF family members revealed their role in LGG. The TCGA database was used as the training cohort; two CGGA databases and GSE108474 were selected as external validation cohorts. Patients were grouped into cluster 1 and cluster 2, both in the training and validation cohorts, using consensus clustering analysis. The prognosis of patients in cluster 1 is significantly better than that in cluster 2. Meanwhile, biofunction prediction was further introduced to explore the potential mechanisms that led to differences in survival outcomes. Patients in Cluster 2 showed more complicated immunocytes infiltration and highly immunosuppressive features than cluster 1. Enrichment pathways such as negative regulation of mast cell activation, DNA replication, mismatch repair, Th17 cell differentiation, antigen processing and presentation, dendritic cell antigen processing and presentation, dendritic cell differentiation were also enriched in cluster 2 patients. For the last, the main contributors were distinguished by employing a machine learning algorithm. A lot of targeted and small molecule drugs that are sensitive to patients in cluster 2 were predicted. Importantly, we discovered TRIM8, DTX2, and TRAF5 as the most vital contributors from the RNF family, which were related to immune infiltration in LGG tumor immune landscape. In this study, we demonstrated the predicted role of RNF proteins in LGG. In addition, we found out three markers among RNF proteins that are closely related to the immune aspects of LGG, which might serve as novel therapeutic targets for immunotherapy in the future.", "claims": [{"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35223862", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Kaplan-Meier analysis in the TCGA database between two clusters showed that patients in cluster 1 had a better prognosis than cluster 2 during the overall survival time (p < 0.0001; Figure 2C).", "kind": "quantitative", "target": {"value": 0.0001, "unit": "p-value", "tolerance": null, "source": "Kaplan-Meier analysis in the TCGA database between two clusters showed that patients in cluster 1 had a better prognosis than cluster 2 during the overall survival time (p < 0.0001; Figure 2C)."}, "evidence": [{"asset": "source:pmid:35223862", "locator": "sections[11] \"Clustering Model Based on RNF Genes Identified Two Clusters with Distinct Outcomes and Clinicopathological Features\" paragraph 2", "quote": "Kaplan-Meier analysis in the TCGA database between two clusters showed that patients in cluster 1 had a better prognosis than cluster 2 during the overall survival time (p < 0.0001; Figure 2C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Kaplan-Meier analysis in the TCGA database between two clusters showed that patients in cluster 1 had a better prognosis than cluster 2 during the overall survival time (p < 0.0001; Figure 2C).", "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:35223862"], "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:GSE108474"], "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:GSE108474"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35223862", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcell.2021.754873", "sha256": 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directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2899178", "GSM2899179", "GSM2899180", "GSM2899181", "GSM2899182", "GSM2899183", "GSM2899184", "GSM2899185", "GSM2899186", "GSM2899187", "GSM2899188", "GSM2899189", "GSM2899190", "GSM2899191", "GSM2899192", "GSM2899193", "GSM2899194", "GSM2899195", "GSM2899196", "GSM2899197", "GSM2899198", "GSM2899199", "GSM2899200", "GSM2899201", "GSM2899202", "GSM2899203", "GSM2899204", "GSM2899205", "GSM2899206", "GSM2899207", "GSM2899208", "GSM2899209", "GSM2899210", "GSM2899211", "GSM2899212", "GSM2899213", "GSM2899214", "GSM2899215", "GSM2899216", "GSM2899217", "GSM2899218", "GSM2899219", "GSM2899220", 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