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pmid:31632497

Combined Therapy Sensitivity Index Based on a 13-Gene Signature Predicts Prognosis for IDH Wild-type and MGMT Promoter Unmethylated Glioblastoma Patients.

Ningrong Ye · Nian Jiang · Chengyuan Feng · Feiyifan Wang · Hanwen Zhang · Harrusin Xiao Bai · Li Yang · Yandong Su · Chunhai Huang · Siyi Wanggou · Xuejun Li

Journal of Cancer · 2019 doi:10.7150/jca.30614

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pmid:31632497
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title
Combined Therapy Sensitivity Index Based on a 13-Gene Signature Predicts Prognosis for IDH Wild-type and MGMT Promoter Unmethylated Glioblastoma Patients.
doi
10.7150/jca.30614
pmid
31632497
authors array · 11 items
[0]
Ningrong Ye
[1]
Nian Jiang
[2]
Chengyuan Feng
[3]
Feiyifan Wang
[4]
Hanwen Zhang
[5]
Harrusin Xiao Bai
[6]
Li Yang
[7]
Yandong Su
[8]
Chunhai Huang
[9]
Siyi Wanggou
[10]
Xuejun Li
journal
Journal of Cancer
year
2019
abstract
Glioblastoma (GBM) is one of the lethal tumors with poor prognosis. However, prognostic prediction approaches need to be further explored. Therefore, we developed an evaluation system that could be used for prognostic prediction of GBM patients. Published mRNA expression datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) were analyzed. Quantitative Realtime-PCR of signature genes and molecular aberrations of 178 Xiangya GBM patients were used for confirmation. Gene set enrichment analysis (GSEA) was performed for functional annotation. As a result, we established a 13-gene signature which named Combined Therapy Sensitivity Index (CTSI). Based on a cutoff point, we divided patients into high-risk group and low-risk group. Based on Kaplan-Meier analysis and multivariate Cox regression analysis, we found that patients in the high-risk group had a shorter overall survival time than patients in the low-risk group (p<0.001 in TCGA and CGGA datasets, p=0.047 in GSE4271 dataset, p=0.008 in Xiangya GBM cohort, HR: 1.65-3.42). By comparing the status of IDH mutation, TERT promoter mutation (TERTp-mut) and MGMT promoter methylation, CTSI was predictable in IDH wild-type (IDH-wt)/MGMT promoter unmethylated (MGMTp-unmeth) patients (p=0.037 in IDH-wt/TERTp-mut/MGMTp-unmeth subgroup, HR: 1.98; p=0.032 in IDH-wt/TERTp-wt/MGMTp-unmeth subgroup, HR: 2.09). Based on GESA, the Gene Ontology (GO) gene sets were enriched differently between CTSI high-risk and low-risk groups. Our results showed CTSI risk score can predict the prognosis of IDH-wt/MGMTp-unmeth GBM patients. Based on CTSI, combined with the status of IDH mutation, TERT promoter mutation and MGMT promoter methylation, a stepwise prognosis evaluation system which can provide precise prognosis prediction for GBM patients was established.
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The Kaplan-Meier method was used to estimate survival time for all the datasets and Xiangya GBM cohort.
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GBM gene expression profiles and corresponding clinical data were obtained from three public databases: the TCGA dataset (http://cancergenome.nih.gov), the GEO GSE4271 dataset (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4271) and the CGGA dataset (http://cgga.org.cn).
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sections[11] "Gene expression datasets and clinical data" paragraph 2
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GBM gene expression profiles and corresponding clinical data were obtained from three public databases: the TCGA dataset (http://cancergenome.nih.gov), the GEO GSE4271 dataset (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4271) and the CGGA dataset (http://cgga.org.cn).
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Identification of signature genes for CTSI risk scoring model
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Cox proportional hazard model for overall survival
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GSE4271 dataset
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0.047*
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Xiangya GBM cohort
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[1]
Gender
[2]
-0.55
[3]
0.45
[4]
0.221
[5]
0.58 (0.24-1.39)
[6]
[7]
[8]
[9]
[35] array · 10 items
[0]
[1]
KPS
[2]
-0.48
[3]
0.21
[4]
0.021*
[5]
0.62 (0.41-0.93)
[6]
-0.48
[7]
0.21
[8]
0.021*
[9]
0.62 (0.41-0.93)
[36] array · 10 items
[0]
[1]
Surgical Resection
[2]
0.01
[3]
0.32
[4]
0.970
[5]
1.01 (0.54-1.88)
[6]
[7]
[8]
[9]
[37] array · 10 items
[0]
[1]
Treatment modality
[2]
-0.82
[3]
0.22
[4]
<0.001*
[5]
0.44 (0.29-0.68)
[6]
-0.82
[7]
0.22
[8]
<0.001*
[9]
0.44 (0.29-0.67)
[38] array · 10 items
[0]
[1]
CTSI risk score
[2]
0.52
[3]
0.19
[4]
0.008*
[5]
1.68 (1.14-2.46)
[6]
0.52
[7]
0.19
[8]
0.008*
[9]
1.68 (1.15-2.46)
[39] array · 10 items
[0]
[1]
TERT promotermutation
[2]
0.62
[3]
0.20
[4]
0.003*
[5]
1.85 (1.24-2.76)
[6]
0.61
[7]
0.20
[8]
0.003*
[9]
1.85 (1.24-2.75)
[40] array · 10 items
[0]
[1]
MGMT promoter methylation
[2]
-0.98
[3]
0.24
[4]
<0.001*
[5]
0.38 (0.23-0.61)
[6]
-0.98
[7]
0.24
[8]
<0.001*
[9]
0.38 (0.23-0.61)
[41] array · 10 items
[0]
[1]
IDH mutation
[2]
-1.98
[3]
0.62
[4]
0.002*
[5]
0.14 (0.04-0.47)
[6]
-1.97
[7]
0.62
[8]
0.001*
[9]
0.14 (0.04-0.47)
[42] array · 3 items
[0]
[1]
[2]
No. of subject=178, No. of event=122, No. of censored=56, Log likelihood=1014.674
locator
section[3]/table-wrap[1]#T1
[3] object · 16 fields
id
asset:table:pmid:31632497:2
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table
format
jats-table
media_type
application/vnd.jats.table+json
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null
sha256
sha256:420b3685e0620c612f238d5fbea7660526256ac05f80e917e6aeb355ef5924cd
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1029
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read_table
reader_status
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section[7]/table-wrap[1]#T2
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null
note
Cox proportional hazard model for IDH wildtype, TERT promoter mutated and MGMT promoter unmethylated patients (No. of subject=58, No. of event=44, No. of censored=14, Log likelihood=269.149).
structure object · 5 fields
pmcid
PMC6775685
section_index
7
section_title
Combined CTSI risk score and TERT promoter mutation for prognosis prediction in IDH-wt and MGMTp-unmeth patients
row_count
8
column_count
10
table object · 8 fields
label
Table 2
caption
Cox proportional hazard model for IDH wildtype, TERT promoter mutated and MGMT promoter unmethylated patients (No. of subject=58, No. of event=44, No. of censored=14, Log likelihood=269.149).
rows array · 8 items
[0] array · 4 items
[0]
[1]
[2]
Univariate Cox regressionMethod: Enter
[3]
Multivariate Cox regressionMethod: Backward likewise
[1] array · 10 items
[0]
[1]
[2]
Co.ef
[3]
Std.Err
[4]
P value
[5]
HR (95% CI)
[6]
Co.ef
[7]
Std.Err
[8]
P value
[9]
HR (95% CI)
[2] array · 10 items
[0]
[1]
Age
[2]
0.05
[3]
0.37
[4]
0.895
[5]
1.05 (0.51-2.18)
[6]
[7]
[8]
[9]
[3] array · 10 items
[0]
[1]
Gender
[2]
0.28
[3]
0.35
[4]
0.415
[5]
1.33 (0.67-2.66)
[6]
[7]
[8]
[9]
[4] array · 10 items
[0]
[1]
KPS
[2]
-0.01
[3]
0.33
[4]
0.969
[5]
0.98 (0.51-1.92)
[6]
[7]
[8]
[9]
[5] array · 10 items
[0]
[1]
Surgical Resection
[2]
-0.44
[3]
0.58
[4]
0.450
[5]
0.65 (0.21-1.99)
[6]
[7]
[8]
[9]
[6] array · 10 items
[0]
[1]
Treatment modality
[2]
-1.19
[3]
0.38
[4]
0.002*
[5]
0.30 (0.14-0.65)
[6]
-1.06
[7]
0.33
[8]
0.001*
[9]
0.35 (0.18-0.67)
[7] array · 10 items
[0]
[1]
CTSI risk score
[2]
0.63
[3]
0.37
[4]
0.091
[5]
1.87 (0.90-3.86)
[6]
0.68
[7]
0.33
[8]
0.037*
[9]
1.98 (1.04-3.75)
locator
section[7]/table-wrap[1]#T2
[4] object · 16 fields
id
asset:table:pmid:31632497:3
role
table
format
jats-table
media_type
application/vnd.jats.table+json
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null
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sha256:d6ed8170cd01b4ffe1d5f88b669ca6bbaef15431718267ca63e8b17eedf7b570
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1063
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read_table
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section[7]/table-wrap[2]#T3
version
null
note
Cox proportional hazard model for IDH wildtype, TERT promoter wildtype and MGMT promoter unmethylated patients (No. of subject=67, No. of event=46, No. of censored=21, Log likelihood=293.099).
structure object · 5 fields
pmcid
PMC6775685
section_index
7
section_title
Combined CTSI risk score and TERT promoter mutation for prognosis prediction in IDH-wt and MGMTp-unmeth patients
row_count
8
column_count
10
table object · 8 fields
label
Table 3
caption
Cox proportional hazard model for IDH wildtype, TERT promoter wildtype and MGMT promoter unmethylated patients (No. of subject=67, No. of event=46, No. of censored=21, Log likelihood=293.099).
rows array · 8 items
[0] array · 4 items
[0]
[1]
[2]
Univariate Cox regressionMethod: Enter
[3]
Multivariate Cox regressionMethod: Backward likewise
[1] array · 10 items
[0]
[1]
[2]
Co.ef
[3]
Std.Err
[4]
P value
[5]
HR (95% CI)
[6]
Co.ef
[7]
Std.Err
[8]
P value
[9]
HR (95% CI)
[2] array · 10 items
[0]
[1]
Age
[2]
0.58
[3]
0.33
[4]
0.079
[5]
0.40 (0.21-0.77)
[6]
[7]
[8]
[9]
[3] array · 10 items
[0]
[1]
Gender
[2]
-0.74
[3]
0.36
[4]
0.137
[5]
0.48 (0.24-1.06)
[6]
[7]
[8]
[9]
[4] array · 10 items
[0]
[1]
KPS
[2]
-0.89
[3]
0.34
[4]
0.008*
[5]
0.41 (0.21-0.79)
[6]
-0.91
[7]
0.33
[8]
0.006
[9]
0.40 (0.21-0.77)
[5] array · 10 items
[0]
[1]
Surgical Resection
[2]
-0.47
[3]
0.54
[4]
0.381
[5]
0.63 (0.22-0.79)
[6]
[7]
[8]
[9]
[6] array · 10 items
[0]
[1]
Treatment modality
[2]
-1.34
[3]
0.41
[4]
0.001*
[5]
0.26 (0.12-0.59)
[6]
-1.25
[7]
0.40
[8]
0.002*
[9]
0.29 (0.13-0.63)
[7] array · 10 items
[0]
[1]
CTSI risk score
[2]
0.84
[3]
0.37
[4]
0.022*
[5]
2.32 (1.13-4.76)
[6]
0.74
[7]
0.34
[8]
0.032*
[9]
2.09 (1.07-4.08)
locator
section[7]/table-wrap[2]#T3
gaps array · 2 items
[0]
asset:data:geo:GSE4271 not downloaded
[1]
asset:data:geo:GSE4271 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
[0] object · 10 fields
id
method-1
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survival_analysis
specific
kaplan_meier
label
Survival analysis
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[0]
survival_km
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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 method was used to estimate survival time for all the datasets and Xiangya GBM cohort.
[1] object · 10 fields
id
method-2
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
0.7
band
medium
quote
Cox regression
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gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
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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
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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]
GSE4271
resolved_accessions array · 1 item
[0]
GSE4271
statements array · 1 item
[0]
GBM gene expression profiles and corresponding clinical data were obtained from three public databases: the TCGA dataset (http://cancergenome.nih.gov), the GEO GSE4271 dataset (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4271) and the CGGA dataset (http://cgga.org.cn).
basis
The paper names GSE4271 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]
survival_km
assets array · 5 items
[0]
source:pmid:31632497
[1]
data:geo:GSE4271
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asset:table:pmid:31632497:1
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asset:table:pmid:31632497:2
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asset:table:pmid:31632497:3
steps array · 1 item
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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
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data:geo:GSE4271
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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
2026-10-31T18:16:31Z
independence
single_reader
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method
verbatim
availability
null
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extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.independent_reader
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review.human_critique
execution object · 5 fields
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absent
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not_run
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execution.not_run
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pmid:31632497
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paper
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pmid:31632497
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source:pmid:31632497
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PMID 31632497 full text
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data:geo:GSE4271
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GEO GSE4271
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activity-reading-sci-2026-11-01
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pmid:31632497
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source:pmid:31632497
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PMID 31632497 full text
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GEO GSE4271
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agent:corpus-assay-engine
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agent:minimax-reader
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[0]
urther validation, we performed quantitative real-time PCR for the 13 signature genes and detected the
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t outcome (Figure 3I). Materials and Methods Microarray data processing The Robust Multichip Average
[1]
justment 37. The probes (or probe sets) from Affymetrix HG-U133a were re-mapped to the human genome
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The Kaplan-Meier method was used to estimate survival time for all the datasets and Xiangya GBM cohort.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31632497", "kind": "science-record", "revision": 7, "content_hash": "sha256:bc18b20ff273fb18f366980f565f19f392d92014cb1ae62fa5e27f8c436f2387", "created_at": "2026-11-01T15:40:50Z", "updated_at": "2026-11-01T21:22:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Combined Therapy Sensitivity Index Based on a 13-Gene Signature Predicts Prognosis for IDH Wild-type and MGMT Promoter Unmethylated Glioblastoma Patients.", "doi": "10.7150/jca.30614", "pmid": "31632497", "authors": ["Ningrong Ye", "Nian Jiang", "Chengyuan Feng", "Feiyifan Wang", "Hanwen Zhang", "Harrusin Xiao Bai", "Li Yang", "Yandong Su", "Chunhai Huang", "Siyi Wanggou", "Xuejun Li"], "journal": "Journal of Cancer", "year": 2019, "abstract": "Glioblastoma (GBM) is one of the lethal tumors with poor prognosis. However, prognostic prediction approaches need to be further explored. Therefore, we developed an evaluation system that could be used for prognostic prediction of GBM patients. Published mRNA expression datasets from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) were analyzed. Quantitative Realtime-PCR of signature genes and molecular aberrations of 178 Xiangya GBM patients were used for confirmation. Gene set enrichment analysis (GSEA) was performed for functional annotation. As a result, we established a 13-gene signature which named Combined Therapy Sensitivity Index (CTSI). Based on a cutoff point, we divided patients into high-risk group and low-risk group. Based on Kaplan-Meier analysis and multivariate Cox regression analysis, we found that patients in the high-risk group had a shorter overall survival time than patients in the low-risk group (p<0.001 in TCGA and CGGA datasets, p=0.047 in GSE4271 dataset, p=0.008 in Xiangya GBM cohort, HR: 1.65-3.42). By comparing the status of IDH mutation, TERT promoter mutation (TERTp-mut) and MGMT promoter methylation, CTSI was predictable in IDH wild-type (IDH-wt)/MGMT promoter unmethylated (MGMTp-unmeth) patients (p=0.037 in IDH-wt/TERTp-mut/MGMTp-unmeth subgroup, HR: 1.98; p=0.032 in IDH-wt/TERTp-wt/MGMTp-unmeth subgroup, HR: 2.09). Based on GESA, the Gene Ontology (GO) gene sets were enriched differently between CTSI high-risk and low-risk groups. Our results showed CTSI risk score can predict the prognosis of IDH-wt/MGMTp-unmeth GBM patients. Based on CTSI, combined with the status of IDH mutation, TERT promoter mutation and MGMT promoter methylation, a stepwise prognosis evaluation system which can provide precise prognosis prediction for GBM patients was established.", "claims": [{"id": "claim-method", "statement": "The Kaplan-Meier method was used to estimate survival time for all the datasets and Xiangya GBM cohort.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31632497", "locator": "sections[18] \"Statistical analysis\" paragraph 4", "quote": "The Kaplan-Meier method was used to estimate survival time for all the datasets and Xiangya GBM cohort."}], "state": "complete"}, {"id": "claim-data-access", "statement": "GBM gene expression profiles and corresponding clinical data were obtained from three public databases: the TCGA dataset (http://cancergenome.nih.gov), the GEO GSE4271 dataset (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4271) and the CGGA dataset (http://cgga.org.cn).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31632497", "locator": "sections[11] \"Gene expression datasets and clinical data\" paragraph 2", "quote": "GBM gene expression profiles and corresponding clinical data were obtained from three public databases: the TCGA dataset (http://cancergenome.nih.gov), the GEO GSE4271 dataset (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE4271) and the CGGA dataset (http://cgga.org.cn)."}], "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:31632497"], "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. 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