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pmid:36639648

A meta-validated immune infiltration-related gene model predicts prognosis and immunotherapy sensitivity in HNSCC.

Yinghe Ding · Ling Chu · Qingtai Cao · Hanyu Lei · Xinyu Li · Quan Zhuang

BMC cancer · 2023 doi:10.1186/s12885-023-10532-y

Paper

complete

Experiment

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Data

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pmid:36639648
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title
A meta-validated immune infiltration-related gene model predicts prognosis and immunotherapy sensitivity in HNSCC.
doi
10.1186/s12885-023-10532-y
pmid
36639648
authors array · 6 items
[0]
Yinghe Ding
[1]
Ling Chu
[2]
Qingtai Cao
[3]
Hanyu Lei
[4]
Xinyu Li
[5]
Quan Zhuang
journal
BMC cancer
year
2023
abstract
BACKGROUND: Tumor microenvironment (TME) is of great importance to regulate the initiation and advance of cancer. The immune infiltration patterns of TME have been considered to impact the prognosis and immunotherapy sensitivity in Head and Neck squamous cell carcinoma (HNSCC). Whereas, specific molecular targets and cell components involved in the HNSCC tumor microenvironment remain a twilight zone. METHODS: Immune scores of TCGA-HNSCC patients were calculated via ESTIMATE algorithm, followed by weighted gene co-expression network analysis (WGCNA) to filter immune infiltration-related gene modules. Univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression were applied to construct the prognostic model. The predictive capacity was validated by meta-analysis including external dataset GSE65858, GSE41613 and GSE686. Model candidate genes were verified at mRNA and protein levels using public database and independent specimens of immunohistochemistry. Immunotherapy-treated cohort GSE159067, TIDE and CIBERSORT were used to evaluate the features of immunotherapy responsiveness and immune infiltration in HNSCC. RESULTS: Immune microenvironment was significantly associated with the prognosis of HNSCC patients. Total 277 immune infiltration-related genes were filtered by WGCNA and involved in various immune processes. Cox regression identified nine prognostic immune infiltration-related genes (MORF4L2, CTSL1, TBC1D2, C5orf15, LIPA, WIPF1, CXCL13, TMEM173, ISG20) to build a risk score. Most candidate genes were highly expressed in HNSCC tissues at mRNA and protein levels. Survival meta-analysis illustrated high prognostic accuracy of the model in the discovery cohort and validation cohort. Higher proportion of progression-free outcomes, lower TIDE scores and higher expression levels of immune checkpoint genes indicated enhanced immunotherapy responsiveness in low-risk patients. Decreased memory B cells, CD8+ T cells, follicular helper T cells, regulatory T cells, and increased activated dendritic cells and activated mast cells were identified as crucial immune cells in the TME of high-risk patients. CONCLUSIONS: The immune infiltration-related gene model was well-qualified and provided novel biomarkers for the prognosis of HNSCC.
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We used univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression to filter significant prognostic genes from immune infiltration-related gene modules.
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sections[8] "Nine-gene model of HNSCC based on immune infiltration-related prognostic genes" paragraph 2
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We used univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression to filter significant prognostic genes from immune infiltration-related gene modules.
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sections[31] "notes" paragraph 1
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Data analyzed in this study is publicly available from TCGA (expression profiles from the Broad GDAC firehose and phenotypes from the UCSC Xena) and GEO database.
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The nine-gene prognostic model achieved 1-, 3-, and 5-year AUCs of 0.698, 0.715, and 0.661, respectively, in the TCGA-HNSCC cohort.
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sections[19] "Construction of a nine-gene prognostic model for survival prediction of HNSCC" paragraph 3
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The AUCs corresponding to 1, 3, and 5 years of survival were 0.698, 0.715, 0.661, respectively, which suggested high sensitivity and specificity of the nine-gene prognostic model (Fig. 4J).
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The nine-gene prognostic model achieved 1-, 3-, and 5-year AUCs of 0.698, 0.715, and 0.661, respectively, in the TCGA-HNSCC cohort.
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GSM1607904
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[222]
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[223]
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[224]
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GSM1607910
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[228]
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[248]
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[251]
GSM1607935
[252]
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[254]
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GSM1607944
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[262]
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[264]
GSM1607948
[265]
GSM1607949
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GSM1607950
[267]
GSM1607951
[268]
GSM1607952
[269]
GSM1607953
sample_count
270
group_sizes
null
group_sizes_basis
null
platform
10558
taxon
Homo sapiens
title
Gene expression patterns and TP53 mutations are associated with HPV RNA status, lymph node metastasis, and survival in head and neck cancer
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[4] object · 15 fields
id
data:geo:GSE686
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=GSE686
sha256
null
bytes
null
access
open
state
resolved
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null
reader_status
reader_required
identifier
GSE686
version
null
note
Data analyzed in this study is publicly available from TCGA (expression profiles from the Broad GDAC firehose and phenotypes from the UCSC Xena) and GEO database.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
Data analyzed in this study is publicly available from TCGA (expression profiles from the Broad GDAC firehose and phenotypes from the UCSC Xena) and GEO database.
access_statement_kind
data_availability_statement
sample_accessions array · 78 items
[0]
GSM10542
[1]
GSM10544
[2]
GSM10548
[3]
GSM10550
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GSM10551
[5]
GSM10552
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GSM10554
[7]
GSM10556
[8]
GSM10558
[9]
GSM10559
[10]
GSM10560
[11]
GSM10561
[12]
GSM10562
[13]
GSM10563
[14]
GSM10564
[15]
GSM10565
[16]
GSM10566
[17]
GSM10613
[18]
GSM10614
[19]
GSM10615
[20]
GSM10616
[21]
GSM10617
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GSM10619
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GSM10620
[25]
GSM10621
[26]
GSM10622
[27]
GSM10623
[28]
GSM10624
[29]
GSM10625
[30]
GSM10626
[31]
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[32]
GSM10628
[33]
GSM10629
[34]
GSM10630
[35]
GSM10631
[36]
GSM10632
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[38]
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[39]
GSM10635
[40]
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[41]
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[42]
GSM10638
[43]
GSM10639
[44]
GSM10640
[45]
GSM10641
[46]
GSM10642
[47]
GSM10643
[48]
GSM10644
[49]
GSM10645
[50]
GSM10646
[51]
GSM10647
[52]
GSM10648
[53]
GSM10649
[54]
GSM10650
[55]
GSM10651
[56]
GSM10652
[57]
GSM10653
[58]
GSM10654
[59]
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[60]
GSM10656
[61]
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[63]
GSM10659
[64]
GSM10660
[65]
GSM10661
[66]
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[67]
GSM10663
[68]
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[69]
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[70]
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[71]
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[72]
GSM10668
[73]
GSM10669
[74]
GSM10670
[75]
GSM10671
[76]
GSM10672
[77]
GSM10673
sample_count
78
group_sizes
null
group_sizes_basis
null
platform
503
taxon
Homo sapiens
title
Gene Expression Profiles of Head and Neck Squamous Cell Carcinoma (HNSCC) primary tumors
resolution_checked_at
2026-11-01T18:46:34Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 8 items
[0]
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[1]
asset:data:geo:GSE159067 licence not read
[2]
asset:data:geo:GSE41613 not downloaded
[3]
asset:data:geo:GSE41613 licence not read
[4]
asset:data:geo:GSE65858 not downloaded
[5]
asset:data:geo:GSE65858 licence not read
[6]
asset:data:geo:GSE686 not downloaded
[7]
asset:data:geo:GSE686 licence not read
analysis object · 4 fields
state
partial
methods array · 5 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
We used univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression to filter significant prognostic genes from immune infiltration-related gene modules.
[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
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two_or_more_groups_continuous
evidence object · 3 fields
score
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high
quote
Wilcoxon
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id
method-3
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survival_analysis
specific
kaplan_meier
label
Survival analysis
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[0]
survival_km
missing_operations array · 0 items
parameters object · 1 field
hazard_ratio
eier survival curve and hazard ratio (HR) based on TCGA-HNSC
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
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Kaplan-Meier
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id
method-4
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survival_analysis
specific
log_rank_test
label
Survival analysis
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[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
[4] object · 10 fields
id
method-5
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
pathway enrichment
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
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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
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expressible
true
required_operations array · 1 item
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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 · 4 items
[0]
GSE65858
[1]
GSE41613
[2]
GSE686
[3]
GSE159067
resolved_accessions array · 4 items
[0]
GSE65858
[1]
GSE41613
[2]
GSE686
[3]
GSE159067
statements array · 1 item
[0]
Data analyzed in this study is publicly available from TCGA (expression profiles from the Broad GDAC firehose and phenotypes from the UCSC Xena) and GEO database.
basis
The paper names GSE65858, GSE41613, GSE686, GSE159067 in 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 · 2 items
[0]
source:pmid:36639648
[1]
data:geo:GSE159067
steps array · 1 item
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run_analysis
must_build object · 5 fields
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readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE159067
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
2026-11-01T18:23:04Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
12716
completion_tokens
2344
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
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review.independent_reader
[1]
review.machine_critique
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review.human_critique
execution object · 5 fields
state
absent
status
not_run
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null
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gaps array · 1 item
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execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:36639648
type
paper
label
pmid:36639648
[1] object · 3 fields
id
source:pmid:36639648
type
manuscript
label
PMID 36639648 full text
[2] object · 3 fields
id
data:geo:GSE159067
type
dataset
label
GEO GSE159067
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
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id
pmid:36639648
type
paper
label
pmid:36639648
[1] object · 3 fields
id
source:pmid:36639648
type
manuscript
label
PMID 36639648 full text
[2] object · 3 fields
id
data:geo:GSE159067
type
dataset
label
GEO GSE159067
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-36639648
type
extraction
used array · 1 item
[0]
source:pmid:36639648
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE159067
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accession_resolution
used array · 1 item
[0]
data:geo:GSE159067
agent
agent:corpus-assay-engine
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[0] object · 3 fields
id
agent:corpus-assay-engine
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software
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agent:minimax-reader
type
software
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lineage object · 4 fields
parent_id
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null
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[5]
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method.reader_differs_from_extractor
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review.machine_critique
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role
data_generation
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99e1195c7d6f
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support_state
partial
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assay_lexicon
99e1195c7d6f
confidence
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evidence array · 1 item
[0]
public database and independent specimens of immunohistochemistry. Immunotherapy-treated cohort GSE159067, TID
order_basis
paper_text_order:1057
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assay:1
[1] object · 11 fields
role
analysis
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survival_analysis
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f2132e96ae6c7a4e
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cox_ph
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dsl_catalogue
f2132e96ae6c7a4e
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We used univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression to filter significant prognostic genes from immune infiltration-related gene modules.
order_basis
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36639648", "kind": "science-record", "revision": 3, "content_hash": "sha256:9bfc7c1c2232fab03a01ca506336713a9bbc7a3d117ed63c1c7c2d4808b5e2e3", "created_at": "2026-11-01T19:01:11Z", "updated_at": "2026-11-01T22:08:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A meta-validated immune infiltration-related gene model predicts prognosis and immunotherapy sensitivity in HNSCC.", "doi": "10.1186/s12885-023-10532-y", "pmid": "36639648", "authors": ["Yinghe Ding", "Ling Chu", "Qingtai Cao", "Hanyu Lei", "Xinyu Li", "Quan Zhuang"], "journal": "BMC cancer", "year": 2023, "abstract": "BACKGROUND: Tumor microenvironment (TME) is of great importance to regulate the initiation and advance of cancer. The immune infiltration patterns of TME have been considered to impact the prognosis and immunotherapy sensitivity in Head and Neck squamous cell carcinoma (HNSCC). Whereas, specific molecular targets and cell components involved in the HNSCC tumor microenvironment remain a twilight zone.\nMETHODS: Immune scores of TCGA-HNSCC patients were calculated via ESTIMATE algorithm, followed by weighted gene co-expression network analysis (WGCNA) to filter immune infiltration-related gene modules. Univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression were applied to construct the prognostic model. The predictive capacity was validated by meta-analysis including external dataset GSE65858, GSE41613 and GSE686. Model candidate genes were verified at mRNA and protein levels using public database and independent specimens of immunohistochemistry. Immunotherapy-treated cohort GSE159067, TIDE and CIBERSORT were used to evaluate the features of immunotherapy responsiveness and immune infiltration in HNSCC.\nRESULTS: Immune microenvironment was significantly associated with the prognosis of HNSCC patients. Total 277 immune infiltration-related genes were filtered by WGCNA and involved in various immune processes. Cox regression identified nine prognostic immune infiltration-related genes (MORF4L2, CTSL1, TBC1D2, C5orf15, LIPA, WIPF1, CXCL13, TMEM173, ISG20) to build a risk score. Most candidate genes were highly expressed in HNSCC tissues at mRNA and protein levels. Survival meta-analysis illustrated high prognostic accuracy of the model in the discovery cohort and validation cohort. Higher proportion of progression-free outcomes, lower TIDE scores and higher expression levels of immune checkpoint genes indicated enhanced immunotherapy responsiveness in low-risk patients. Decreased memory B cells, CD8+ T cells, follicular helper T cells, regulatory T cells, and increased activated dendritic cells and activated mast cells were identified as crucial immune cells in the TME of high-risk patients.\nCONCLUSIONS: The immune infiltration-related gene model was well-qualified and provided novel biomarkers for the prognosis of HNSCC.", "claims": [{"id": "claim-method", "statement": "We used univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression to filter significant prognostic genes from immune infiltration-related gene modules.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36639648", "locator": "sections[8] \"Nine-gene model of HNSCC based on immune infiltration-related prognostic genes\" paragraph 2", "quote": "We used univariate, the least absolute shrinkage and selection operator (LASSO), and multivariate cox regression to filter significant prognostic genes from immune infiltration-related gene modules."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data analyzed in this study is publicly available from TCGA (expression profiles from the Broad GDAC firehose and phenotypes from the UCSC Xena) and GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36639648", "locator": "sections[31] \"notes\" paragraph 1", "quote": "Data analyzed in this study is publicly available from TCGA (expression profiles from the Broad GDAC firehose and phenotypes from the UCSC Xena) and GEO database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The nine-gene prognostic model achieved 1-, 3-, and 5-year AUCs of 0.698, 0.715, and 0.661, respectively, in the TCGA-HNSCC cohort.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36639648", "locator": "sections[19] \"Construction of a nine-gene prognostic model for survival prediction of HNSCC\" paragraph 3", "quote": "The AUCs corresponding to 1, 3, and 5 years of survival were 0.698, 0.715, 0.661, respectively, which suggested high sensitivity and specificity of the nine-gene prognostic model (Fig. 4J)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The nine-gene prognostic model achieved 1-, 3-, and 5-year AUCs of 0.698, 0.715, and 0.661, respectively, in the TCGA-HNSCC cohort.", "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:36639648"], "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:GSE159067"], "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:GSE159067"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36639648", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12885-023-10532-y", "sha256": 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