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pmid:37637034

Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer.

Xiaolong Jia · Dongxu Zhang · Cheng Zhou · Zejun Yan · Zhaohui Jiang · Liping Xie · Junhui Jiang

Frontiers in oncology · 2023 doi:10.3389/fonc.2023.1175183

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Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer.
doi
10.3389/fonc.2023.1175183
pmid
37637034
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[0]
Xiaolong Jia
[1]
Dongxu Zhang
[2]
Cheng Zhou
[3]
Zejun Yan
[4]
Zhaohui Jiang
[5]
Liping Xie
[6]
Junhui Jiang
journal
Frontiers in oncology
year
2023
abstract
Background: The role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known. Methods: A pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs. Results: The pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed. Conclusions: This study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.
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The univariate Cox regression analysis found 35 genes to be significantly associated with the prognosis of BLCA ( Supplementary Table 2 ). After calculation, the combinational algorithms of RF and Ridge exhibited the best performance ( Figure 9D ), identifying a total of 21 genes enrolled in the EPHB6-related Genes signature (EBGs; Supplementary Table 2 ).
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sections[21] "Prognostic significance of EPHB6 in BLCA" paragraph 2
quote
The univariate Cox regression analysis found 35 genes to be significantly associated with the prognosis of BLCA ( Supplementary Table 2 ). After calculation, the combinational algorithms of RF and Ridge exhibited the best performance ( Figure 9D ), identifying a total of 21 genes enrolled in the EPHB6-related Genes signature (EBGs; Supplementary Table 2 ).
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The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
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Moreover, the performance of EBGs signature was validated in other four independent BLCA cohorts, and consistently higher EBGs score indicated an inferior OS.
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Moreover, the performance of EBGs signature was validated in other four independent BLCA cohorts, and consistently higher EBGs score indicated an inferior OS.
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sections[21] "Prognostic significance of EPHB6 in BLCA" paragraph 2
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All the AUC values of EBGs signature in predicting prognosis for patients with BLCA were approximately 0.65 ( Figure 9E ).
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Moreover, the performance of EBGs signature was validated in other four independent BLCA cohorts, and consistently higher EBGs score indicated an inferior OS.
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570
taxon
Homo sapiens
title
Combination of a novel gene expression signature with a clinical nomogram improves the prediction of survival in high-risk bladder cancer  
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
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licence_read
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[4] object · 15 fields
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The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
structure object · 15 fields
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GEO accession URL
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The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
access_statement_kind
data_availability_statement
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[129]
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[130]
GSM806933
sample_count
131
group_sizes
null
group_sizes_basis
null
platform
6947
taxon
Homo sapiens
title
Integrated genomic and gene expression profiling identifies two major gene/genomic circuits operating in urothelial carcinoma (gene expression)
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
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licence_read
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[5] object · 15 fields
id
data:geo:GSE32894
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raw
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application/vnd.ncbi.geo-series+json
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GSE32894
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null
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The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
access_statement_kind
data_availability_statement
sample_accessions array · 308 items
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[40]
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[45]
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[50]
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[51]
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[52]
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[53]
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[54]
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[56]
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[57]
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[58]
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[59]
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[60]
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[61]
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[62]
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[63]
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[64]
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[65]
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[66]
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[67]
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[68]
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[69]
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[70]
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[71]
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[72]
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[73]
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[74]
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[75]
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[76]
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[77]
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[78]
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[79]
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[80]
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[81]
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[82]
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[83]
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[84]
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[85]
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[86]
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[87]
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[88]
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[89]
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[90]
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[91]
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[92]
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[93]
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[94]
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[95]
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[96]
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[97]
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[98]
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[99]
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[100]
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[101]
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[102]
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[103]
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[104]
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[105]
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[106]
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[107]
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[108]
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[109]
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[110]
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[111]
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[112]
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[113]
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[114]
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[115]
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[116]
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[117]
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[118]
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[119]
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[120]
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[121]
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[122]
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[123]
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[124]
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[140]
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[144]
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[145]
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[146]
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[147]
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[155]
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[156]
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sample_count
308
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null
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null
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6947
taxon
Homo sapiens
title
A Molecular Taxonomy of Urothelial Carcinoma
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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gaps array · 10 items
[0]
asset:data:geo:GSE13507 not downloaded
[1]
asset:data:geo:GSE13507 licence not read
[2]
asset:data:geo:GSE188715 not downloaded
[3]
asset:data:geo:GSE188715 licence not read
[4]
asset:data:geo:GSE31684 not downloaded
[5]
asset:data:geo:GSE31684 licence not read
[6]
asset:data:geo:GSE32548 not downloaded
[7]
asset:data:geo:GSE32548 licence not read
[8]
asset:data:geo:GSE32894 not downloaded
[9]
asset:data:geo:GSE32894 licence not read
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state
complete
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[0] object · 10 fields
id
method-1
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survival_analysis
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cox_proportional_hazards
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Survival analysis
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[0]
cox_ph
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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
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verbatim
quote
The univariate Cox regression analysis found 35 genes to be significantly associated with the prognosis of BLCA ( Supplementary Table 2 ). After calculation, the combinational algorithms of RF and Ridge exhibited the best performance ( Figure 9D ), identifying a total of 21 genes enrolled in the EPHB6-related Genes signature (EBGs; Supplementary Table 2 ).
[1] object · 10 fields
id
method-2
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survival_analysis
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Survival analysis
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[0]
logrank_test
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parameters object · 0 fields
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[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
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high
quote
log-rank
[2] object · 10 fields
id
method-3
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contingency_analysis
specific
chi_square
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Categorical (contingency table) analysis
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[0]
chi_square_test
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parameters object · 0 fields
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[0]
categorical_cross_tabulation
evidence object · 3 fields
score
0.8
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high
quote
chi-square
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gaps array · 0 items
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
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Computational analysis platform
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[0]
meta_analysis
[1]
machine_learning
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survival_analysis
[3]
statistical_regression
[4]
pca
[5]
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[6]
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[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 · 5 items
[0]
GSE32548
[1]
GSE13507
[2]
GSE188715
[3]
GSE32894
[4]
GSE31684
resolved_accessions array · 5 items
[0]
GSE32548
[1]
GSE13507
[2]
GSE188715
[3]
GSE32894
[4]
GSE31684
statements array · 1 item
[0]
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
basis
The paper names GSE32548, GSE13507, GSE188715, GSE32894, GSE31684 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
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[0]
cox_ph
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[0]
source:pmid:37637034
[1]
data:geo:GSE13507
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:GSE13507
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
2026-11-01T18:51:58Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
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5
usage object · 3 fields
prompt_tokens
20953
completion_tokens
3063
cached_tokens
128
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[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
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absent
status
not_run
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null
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
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[0] object · 3 fields
id
pmid:37637034
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paper
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pmid:37637034
[1] object · 3 fields
id
source:pmid:37637034
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manuscript
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PMID 37637034 full text
[2] object · 3 fields
id
data:geo:GSE13507
type
dataset
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GEO GSE13507
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
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classification
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[0] object · 3 fields
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pmid:37637034
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paper
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pmid:37637034
[1] object · 3 fields
id
source:pmid:37637034
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manuscript
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PMID 37637034 full text
[2] object · 3 fields
id
data:geo:GSE13507
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dataset
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GEO GSE13507
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agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-37637034
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extraction
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[0]
source:pmid:37637034
agent
agent:minimax-reader
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lineage object · 4 fields
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pmid:37637034
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sha256:f87d6ba2d7d855c609ef256af9d60d081eb8bf08d688b537b51669de54522913
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null
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asset:data:geo:GSE13507 licence not read
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asset:data:geo:GSE13507 not downloaded
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asset:data:geo:GSE188715 licence not read
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asset:data:geo:GSE188715 not downloaded
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asset:data:geo:GSE31684 licence not read
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asset:data:geo:GSE31684 not downloaded
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asset:data:geo:GSE32548 licence not read
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asset:data:geo:GSE32548 not downloaded
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asset:data:geo:GSE32894 licence not read
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asset:data:geo:GSE32894 not downloaded
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assays array · 2 items
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evidence array · 4 items
[0]
to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to va
[1]
Materials and methods Immunohistochemical analysis of EPHB6 and correlation with TME W
[2]
ples (4-µm-thick sections) were subjected to immunohistochemical staining for EPHB6, CD8, CD68 using EPHB6 (a
[3]
, 1:50, Abcam) antibodies, respectively. The immunohistochemical staining method was performed as described p
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paper_text_order:817
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assay:1
[1] object · 11 fields
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The univariate Cox regression analysis found 35 genes to be significantly associated with the prognosis of BLCA ( Supplementary Table 2 ). After calculation, the combinational algorithms of RF and Ridge exhibited the best performance ( Figure 9D ), identifying a total of 21 genes enrolled in the EPHB6-related Genes signature (EBGs; Supplementary Table 2 ).
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37637034", "kind": "science-record", "revision": 4, "content_hash": "sha256:ecf114f923f51816d3ecaa979b7cd309ff24ad12ef9285366d4e009017bb88d9", "created_at": "2026-11-01T19:02:25Z", "updated_at": "2026-11-01T22:52:36Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Eph receptor B6 shapes a cold immune microenvironment, inhibiting anti-cancer immunity and immunotherapy response in bladder cancer.", "doi": "10.3389/fonc.2023.1175183", "pmid": "37637034", "authors": ["Xiaolong Jia", "Dongxu Zhang", "Cheng Zhou", "Zejun Yan", "Zhaohui Jiang", "Liping Xie", "Junhui Jiang"], "journal": "Frontiers in oncology", "year": 2023, "abstract": "Background: The role of Eph receptors and related ephrin (EFN) ligands (as the largest family of transmembrane-bound RTKs) in immunomodulation in many types of cancer, especially bladder cancer (BLCA), is scarcely known.\nMethods: A pan-cancer dataset was retrieved from The Cancer Genome Atlas (TCGA) to explore the relation between Eph receptor/EFN ligand family genes and immunomodulators and tumor-infiltrated immune cells (TIICs). Local BLCA, GSE32894, and GSE31684 cohorts were applied to validate. The IMvigor210 cohort was employed to explore the relationship between EPHB6 and immunotherapy response. Moreover, association between EPHB6 and molecular subtype was investigated to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to validate the correlation between EPHB6 and TIICs.\nResults: The pan-cancer analysis revealed variations in the immunological effects of Eph receptor/EFN ligand family genes across different types of cancer. EPHB6 expression negatively correlated with the expression of the majority of immunomodulators (including HLA and immune checkpoints), and CD8 T cells and macrophages in both the TCGA-BLCA and validation BLCA cohorts, shaping a cold immune microenvironment with inhibited immunity. In the IMvigor210 cohort, patients with high-EPHB6 highly correlated with a non-inflamed, low PD-L1 expression immune phenotype, and correspondingly, with less responders to immunotherapy. The high-EPHB6 group, enriched with the basal subtype, presented significantly fewer TP53 and more FGFR3 genomic alterations. Finally, a novel EPHB6-related Genes signature, with reliable and robust ability in prognosis prediction, was constructed.\nConclusions: This study comprehensively investigated the immunological effects of Eph receptor/EFN ligand family genes pan-cancer, and specially identified the immunosuppressive role of EPHB6 in BLCA. Furthermore, EPHB6 may predict the molecular subtype and prognosis of BLCA, and serve as a novel therapeutic target to improve the sensitivity of immunotherapy.", "claims": [{"id": "claim-method", "statement": "The univariate Cox regression analysis found 35 genes to be significantly associated with the prognosis of BLCA ( Supplementary Table 2 ). After calculation, the combinational algorithms of RF and Ridge exhibited the best performance ( Figure 9D ), identifying a total of 21 genes enrolled in the EPHB6-related Genes signature (EBGs; Supplementary Table 2 ).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37637034", "locator": "sections[21] \"Prognostic significance of EPHB6 in BLCA\" paragraph 2", "quote": "The univariate Cox regression analysis found 35 genes to be significantly associated with the prognosis of BLCA ( Supplementary Table 2 ). After calculation, the combinational algorithms of RF and Ridge exhibited the best performance ( Figure 9D ), identifying a total of 21 genes enrolled in the EPHB6-related Genes signature (EBGs; Supplementary Table 2 )."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37637034", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Moreover, the performance of EBGs signature was validated in other four independent BLCA cohorts, and consistently higher EBGs score indicated an inferior OS.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37637034", "locator": "sections[21] \"Prognostic significance of EPHB6 in BLCA\" paragraph 2", "quote": "Moreover, the performance of EBGs signature was validated in other four independent BLCA cohorts, and consistently higher EBGs score indicated an inferior OS."}, {"asset": "source:pmid:37637034", "locator": "sections[21] \"Prognostic significance of EPHB6 in BLCA\" paragraph 2", "quote": "All the AUC values of EBGs signature in predicting prognosis for patients with BLCA were approximately 0.65 ( Figure 9E )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Moreover, the performance of EBGs signature was validated in other four independent BLCA cohorts, and consistently higher EBGs score indicated an inferior OS.", "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:37637034"], "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:GSE13507"], "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:GSE13507"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37637034", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2023.1175183", "sha256": 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After calculation, the combinational algorithms of RF and Ridge exhibited the best performance ( Figure 9D ), identifying a total of 21 genes enrolled in the EPHB6-related Genes signature (EBGs; Supplementary Table 2 )."}}, {"id": "method-2", "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-3", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "chi-square"}}], "targets": [], "gaps": []}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:37637034", "data:geo:GSE13507"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE13507"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:51:58Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 20953, "completion_tokens": 3063, "cached_tokens": 128}}, "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:37637034", "type": "paper", "label": "pmid:37637034"}, {"id": "source:pmid:37637034", "type": "manuscript", "label": "PMID 37637034 full text"}, {"id": "data:geo:GSE13507", "type": "dataset", "label": "GEO GSE13507"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37637034", "type": "paper", "label": "pmid:37637034"}, {"id": "source:pmid:37637034", "type": "manuscript", "label": "PMID 37637034 full text"}, {"id": "data:geo:GSE13507", "type": "dataset", "label": "GEO GSE13507"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37637034", "type": "extraction", "used": ["source:pmid:37637034"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE13507", "type": "accession_resolution", "used": ["data:geo:GSE13507"], "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:37637034", "parent_hash": "sha256:f87d6ba2d7d855c609ef256af9d60d081eb8bf08d688b537b51669de54522913", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE13507 licence not read", "asset:data:geo:GSE13507 not downloaded", "asset:data:geo:GSE188715 licence not read", "asset:data:geo:GSE188715 not downloaded", "asset:data:geo:GSE31684 licence not read", "asset:data:geo:GSE31684 not downloaded", "asset:data:geo:GSE32548 licence not read", "asset:data:geo:GSE32548 not downloaded", "asset:data:geo:GSE32894 licence not read", "asset:data:geo:GSE32894 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["to explore potential therapeutic strategies. Immunohistochemical staining of CD8 and CD68 was performed to va", "Materials and methods Immunohistochemical analysis of EPHB6 and correlation with TME W", "ples (4-µm-thick sections) were subjected to immunohistochemical staining for EPHB6, CD8, CD68 using EPHB6 (a", ", 1:50, Abcam) antibodies, respectively. The immunohistochemical staining method was performed as described p"], "order_basis": "paper_text_order:817", "id": "assay:1"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The univariate Cox regression analysis found 35 genes to be significantly associated with the prognosis of BLCA ( Supplementary Table 2 ). After calculation, the combinational algorithms of RF and Ridge exhibited the best performance ( Figure 9D ), identifying a total of 21 genes enrolled in the EPHB6-related Genes signature (EBGs; Supplementary Table 2 )."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}