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pmid:33718069

m6A RNA methylation regulators play an important role in the prognosis of patients with testicular germ cell tumor.

Rong Cong · Chengjian Ji · Jiayi Zhang · Qijie Zhang · Xiang Zhou · Liangyu Yao · Jiaochen Luan · Xianghu Meng · Ninghong Song

Translational andrology and urology · 2021 doi:10.21037/tau-20-963

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Experiment

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Data

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Analysis

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pmid:33718069
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2026-11-01T15:41:28Z
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title
m6A RNA methylation regulators play an important role in the prognosis of patients with testicular germ cell tumor.
doi
10.21037/tau-20-963
pmid
33718069
authors array · 9 items
[0]
Rong Cong
[1]
Chengjian Ji
[2]
Jiayi Zhang
[3]
Qijie Zhang
[4]
Xiang Zhou
[5]
Liangyu Yao
[6]
Jiaochen Luan
[7]
Xianghu Meng
[8]
Ninghong Song
journal
Translational andrology and urology
year
2021
abstract
BACKGROUND: N6-methyladenosine (m6A) is found to be associated with promoting tumorigenesis in different types of cancers, however, the function of m6A-related genes in testicular germ cell tumors (TGCT) development remains to be illuminated. This study aimed to investigated the prognostic value of m6A RNA methylation regulators in TGCT. METHODS: We collected TGCT patients' information about clinicopathologic parameters and twenty-two m6A regulatory genes expression from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). We analyzed the differentially expressed m6A RNA methylation regulators between tumor tissues and normal tissues, as well as the correlation of m6A RNA methylation regulators. By using Cox univariate analysis, last absolute shrinkage and selection operator (LASSO) Cox regression algorithm and Cox multivariate proportional hazards regression analysis, a risk score was constructed based on a TCGA training cohort, and further verified in the TCGA testing cohort. Then, univariate and multivariate Cox regression analyses were used to evaluate the relationship between risk score and progression-free survival (PFS) in TGCT. Finally, the six-gene risk score was further verified by two gene expression profiles (GSE3218 and GSE10783) as an independent external validation cohort. RESULTS: Distinct expression patterns of m6A regulatory genes were identified between TGCT tissues and normal tissues in TCGA and GTEx datasets. To predict prognosis of TGCT patients, a risk score was calculated based on six selected m6A RNA methylation regulators (YTHDF1, RBM15, IGF2BP1, ZC3H13, METTL3, and FMR1). Additionally, we found significant differences between the high-risk and low-risk groups in serum marker study levels and histologic subtype. Univariate and multivariate analysis indicated that high risk score was associated with unfavorable PFS. Ultimately, the risk score was further verified by two gene expression profiles (GSE3218 and GSE10783). CONCLUSIONS: Based on six selected m6A RNA methylation regulators, we developed a m6A methylation related risk score that can independently predict the prognosis of TGCT patients, and verify the prediction efficiency in TCGA and GEO datasets. Patients in high-risk group were associated with serum tumor marker study levels beyond the normal limits, non-seminoma, and unfavorable survival time. However, further prospective experiments should be carried out to verify our results.
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To investigate whether risk score was an independent prognostic factor, univariate and multivariate Cox regression analyses were used in the entire TCGA cohort.
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sections[7] "Validation of the prognostic signature" paragraph 3
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To investigate whether risk score was an independent prognostic factor, univariate and multivariate Cox regression analyses were used in the entire TCGA cohort.
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All of these normalized clinical data and RNA-seq data of patients were obtained from TCGA (http://cancergenome.nih.gov/) and GTEx (Genotype-Tissue Expression).
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Validation Set for Prediction of Outcome in Adult Male Germ Cell Tumors
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Expression Profiling of Adult Male Germ Cell Tumors
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Clinical information of included TCGA cohort
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Cox univariate analysis of m6A RNA methylation regulators to investigate the effect of m6A RNA methylation regulators on TGCT prognosis
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Prognostic signature of m6A RNA methylation regulators in TGCT
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Cox univariate analysis of m6A RNA methylation regulators to investigate the effect of m6A RNA methylation regulators on TGCT prognosis
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[8] array · 3 items
[0]
YTHDF2
[1]
0.083202 (0.002673–2.590295)
[2]
0.156363
[9] array · 3 items
[0]
HNRNPA2B1
[1]
0.01239 (0.000016–9.590852)
[2]
0.195735
[10] array · 3 items
[0]
METTL16
[1]
0.268298 (0.028964–2.48528)
[2]
0.246702
[11] array · 3 items
[0]
IGF2BP3
[1]
1.616413 (0.71076–3.676055)
[2]
0.251994
[12] array · 3 items
[0]
IGF2BP1
[1]
2.155541 (0.477137–9.737995)
[2]
0.318165
[13] array · 3 items
[0]
IGF2BP2
[1]
2.368073 (0.430614–13.02274)
[2]
0.321583
[14] array · 3 items
[0]
HNRNPC
[1]
0.058167 (0.000207–16.31963)
[2]
0.322646
[15] array · 3 items
[0]
METTL3
[1]
3.217734 (0.122173–84.74715)
[2]
0.483761
[16] array · 3 items
[0]
YTHDC2
[1]
0.447566 (0.04586–4.367978)
[2]
0.489175
[17] array · 3 items
[0]
YTHDF3
[1]
0.437247 (0.033203–5.75815)
[2]
0.529372
[18] array · 3 items
[0]
FTO
[1]
0.537583 (0.069118–4.181175)
[2]
0.55315
[19] array · 3 items
[0]
WTAP
[1]
0.220542 (0.001001–48.58904)
[2]
0.582888
[20] array · 3 items
[0]
RBM15B
[1]
2.072659 (0.072891–58.9362)
[2]
0.669586
[21] array · 3 items
[0]
YTHDF1
[1]
2.083396 (0.047455–91.46694)
[2]
0.703659
[22] array · 3 items
[0]
METTL14
[1]
0.58829 (0.012586–27.49706)
[2]
0.786803
locator
section[15]/table-wrap[1]#t2
gaps array · 4 items
[0]
asset:data:geo:GSE10783 not downloaded
[1]
asset:data:geo:GSE10783 licence not read
[2]
asset:data:geo:GSE3218 not downloaded
[3]
asset:data:geo:GSE3218 licence not read
analysis object · 4 fields
state
partial
methods array · 4 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
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
To investigate whether risk score was an independent prognostic factor, univariate and multivariate Cox regression analyses were used in the entire TCGA cohort.
[1] object · 10 fields
id
method-2
family
group_comparison
specific
wilcoxon
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
Wilcoxon
[2] object · 10 fields
id
method-3
family
correlation_analysis
specific
pearson
label
Correlation analysis
dsl_operations array · 1 item
[0]
pearson_r
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
band
high
quote
Pearson correlation
[3] object · 10 fields
id
method-4
family
contingency_analysis
specific
chi_square
label
Categorical (contingency table) analysis
dsl_operations array · 1 item
[0]
chi_square_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
categorical_cross_tabulation
evidence object · 3 fields
score
0.8
band
high
quote
chi-square
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
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]
cox_ph
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: cox_proportional_hazards.
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 · 2 items
[0]
GSE3218
[1]
GSE10783
resolved_accessions array · 2 items
[0]
GSE3218
[1]
GSE10783
statements array · 1 item
[0]
All of these normalized clinical data and RNA-seq data of patients were obtained from TCGA (http://cancergenome.nih.gov/) and GTEx (Genotype-Tissue Expression).
basis
The paper names GSE3218, GSE10783 in Gene Expression Omnibus (GEO) 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]
cox_ph
assets array · 4 items
[0]
source:pmid:33718069
[1]
data:geo:GSE10783
[2]
asset:table:pmid:33718069:1
[3]
asset:table:pmid:33718069:2
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:GSE10783
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
2026-10-31T18:28:01Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
null
calls
3
usage object · 3 fields
prompt_tokens
36095
completion_tokens
1395
cached_tokens
784
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:33718069
type
paper
label
pmid:33718069
[1] object · 3 fields
id
source:pmid:33718069
type
manuscript
label
PMID 33718069 full text
[2] object · 3 fields
id
data:geo:GSE10783
type
dataset
label
GEO GSE10783
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:33718069
type
paper
label
pmid:33718069
[1] object · 3 fields
id
source:pmid:33718069
type
manuscript
label
PMID 33718069 full text
[2] object · 3 fields
id
data:geo:GSE10783
type
dataset
label
GEO GSE10783
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-33718069
type
extraction
used array · 1 item
[0]
source:pmid:33718069
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE10783
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE10783
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:33718069
parent_hash
sha256:dc09087d414b1179a5eb9ce1ff090922cd00955870e9461077a8f73fb6283cf1
fork_of
null
gaps array · 9 items
[0]
asset:data:geo:GSE10783 licence not read
[1]
asset:data:geo:GSE10783 not downloaded
[2]
asset:data:geo:GSE3218 licence not read
[3]
asset:data:geo:GSE3218 not downloaded
[4]
execution.not_run
[5]
method.reader_differs_from_extractor
[6]
review.human_critique
[7]
review.independent_reader
[8]
review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_id
rna_seq
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
es All of these normalized clinical data and RNA-seq data of patients were obtained from TCGA (ht
order_basis
paper_text_order:2621
id
assay:1
[1] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
To investigate whether risk score was an independent prognostic factor, univariate and multivariate Cox regression analyses were used in the entire TCGA cohort.
order_basis
consumes_earlier_output
id
assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33718069", "kind": "science-record", "revision": 8, "content_hash": "sha256:8a10f3ac9b5be278661e6fe08015c28e9b025c5a407ef082b1b43284f90405c5", "created_at": "2026-11-01T15:41:28Z", "updated_at": "2026-11-01T22:03:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "m6A RNA methylation regulators play an important role in the prognosis of patients with testicular germ cell tumor.", "doi": "10.21037/tau-20-963", "pmid": "33718069", "authors": ["Rong Cong", "Chengjian Ji", "Jiayi Zhang", "Qijie Zhang", "Xiang Zhou", "Liangyu Yao", "Jiaochen Luan", "Xianghu Meng", "Ninghong Song"], "journal": "Translational andrology and urology", "year": 2021, "abstract": "BACKGROUND: N6-methyladenosine (m6A) is found to be associated with promoting tumorigenesis in different types of cancers, however, the function of m6A-related genes in testicular germ cell tumors (TGCT) development remains to be illuminated. This study aimed to investigated the prognostic value of m6A RNA methylation regulators in TGCT.\nMETHODS: We collected TGCT patients' information about clinicopathologic parameters and twenty-two m6A regulatory genes expression from The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). We analyzed the differentially expressed m6A RNA methylation regulators between tumor tissues and normal tissues, as well as the correlation of m6A RNA methylation regulators. By using Cox univariate analysis, last absolute shrinkage and selection operator (LASSO) Cox regression algorithm and Cox multivariate proportional hazards regression analysis, a risk score was constructed based on a TCGA training cohort, and further verified in the TCGA testing cohort. Then, univariate and multivariate Cox regression analyses were used to evaluate the relationship between risk score and progression-free survival (PFS) in TGCT. Finally, the six-gene risk score was further verified by two gene expression profiles (GSE3218 and GSE10783) as an independent external validation cohort.\nRESULTS: Distinct expression patterns of m6A regulatory genes were identified between TGCT tissues and normal tissues in TCGA and GTEx datasets. To predict prognosis of TGCT patients, a risk score was calculated based on six selected m6A RNA methylation regulators (YTHDF1, RBM15, IGF2BP1, ZC3H13, METTL3, and FMR1). Additionally, we found significant differences between the high-risk and low-risk groups in serum marker study levels and histologic subtype. Univariate and multivariate analysis indicated that high risk score was associated with unfavorable PFS. Ultimately, the risk score was further verified by two gene expression profiles (GSE3218 and GSE10783).\nCONCLUSIONS: Based on six selected m6A RNA methylation regulators, we developed a m6A methylation related risk score that can independently predict the prognosis of TGCT patients, and verify the prediction efficiency in TCGA and GEO datasets. Patients in high-risk group were associated with serum tumor marker study levels beyond the normal limits, non-seminoma, and unfavorable survival time. However, further prospective experiments should be carried out to verify our results.", "claims": [{"id": "claim-method", "statement": "To investigate whether risk score was an independent prognostic factor, univariate and multivariate Cox regression analyses were used in the entire TCGA cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33718069", "locator": "sections[7] \"Validation of the prognostic signature\" paragraph 3", "quote": "To investigate whether risk score was an independent prognostic factor, univariate and multivariate Cox regression analyses were used in the entire TCGA cohort."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All of these normalized clinical data and RNA-seq data of patients were obtained from TCGA (http://cancergenome.nih.gov/) and GTEx (Genotype-Tissue Expression).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33718069", "locator": "sections[3] \"Patient samples\" paragraph 2", "quote": "All of these normalized clinical data and RNA-seq data of patients were obtained from TCGA (http://cancergenome.nih.gov/) and GTEx (Genotype-Tissue Expression)."}], "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:33718069"], "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:GSE10783"], "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:GSE10783"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33718069", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/tau-20-963", "sha256": "sha256:7af09f69ffc21d1c248e8869744593ad0ef47866502484b830037595a4601992", "bytes": 45229, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/tau-20-963", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7947426", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE10783", "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=GSE10783", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE10783", "version": null, "note": "All of these normalized clinical data and RNA-seq data of patients were obtained from TCGA (http://cancergenome.nih.gov/) and GTEx 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"GSM271827", "GSM271828", "GSM271829", "GSM271830", "GSM271831", "GSM271832", "GSM271833", "GSM271834", "GSM271835", "GSM271836", "GSM271837", "GSM271838", "GSM271839", "GSM271840", "GSM271841", "GSM271842", "GSM271843", "GSM271844", "GSM271845", "GSM271846"], "sample_count": 68, "group_sizes": null, "group_sizes_basis": null, "platform": "97;96", "taxon": "Homo sapiens", "title": "Validation Set for Prediction of Outcome in Adult Male Germ Cell Tumors", "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:GSE3218", "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=GSE3218", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE3218", "version": null, "note": "All of 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