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pmid:33557848

Identification of a two-gene prognostic model associated with cytolytic activity for colon cancer.

Xiaoye Jiang · Zhongxiang Jiang · Lichun Xiang · Xuenuo Chen · Jiao Wu · Zheng Jiang

Cancer cell international · 2021 doi:10.1186/s12935-021-01782-6

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Data

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pmid:33557848
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title
Identification of a two-gene prognostic model associated with cytolytic activity for colon cancer.
doi
10.1186/s12935-021-01782-6
pmid
33557848
authors array · 6 items
[0]
Xiaoye Jiang
[1]
Zhongxiang Jiang
[2]
Lichun Xiang
[3]
Xuenuo Chen
[4]
Jiao Wu
[5]
Zheng Jiang
journal
Cancer cell international
year
2021
abstract
BACKGROUND: Increasing evidence has shown that cytolytic activity (CYT) is a new immunotherapy biomarker that characterises the antitumour immune activity of cytotoxic T cells and macrophages. In this study, we established a prognostic model associated with CYT. METHODS: A prognostic model based on CYT-related genes was developed. Furthermore, aberrant expression of genes of the model in colon cancer (CC) was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays. Next, the correlation between the model and T-cell infiltration in the CC microenvironment was analysed. The Tumour Immune Dysfunction and Exclusion (TIDE) algorithm and subclass mapping were used to predict clinical responses to immune checkpoint inhibitors. RESULTS: In total, 280 of the 1418 genes were differentially expressed based on CYT. A prognostic model (including HOXC8 and MS4A2) was developed based on CYT-related genes. The model was validated using the testing set, the whole set and a Gene Expression Omnibus (GEO) cohort (GSE41258). Gene set enrichment analysis (GSEA) and other analyses showed that the levels of immune infiltration and antitumour immune activation in low-risk-score tumours were greater than those in high-risk-score tumours. CC patients with a low-risk-score showed more promise in the response to anti-immune checkpoint therapy. CONCLUSIONS: Overall, our model may precisely predict the overall survival of CC and reflect the strength of antitumour immune activity in the CC microenvironment. Furthermore, the model may be a predictive factor for the response to immunotherapy.
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In univariate and multivariate Cox regression analyses, our model was associated with survival (P = 0.002).
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sections[18] "Relationship between the CYT-related prognostic model and clinicopathological features" paragraph 3
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In univariate and multivariate Cox regression analyses, our model was associated with survival (P = 0.002).
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The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.
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The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.
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The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.
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The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.
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sample_count
585
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene expression Classification of Colon Cancer defines six molecular subtypes with distinct clinical, molecular and survival characteristics [Expression]
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[2] object · 15 fields
id
data:geo:GSE41258
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=GSE41258
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
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version
null
note
The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.
access_statement_kind
data_availability_statement
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sample_count
390
group_sizes
null
group_sizes_basis
null
platform
96
taxon
Homo sapiens
title
Expression data from colorectal cancer patients
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 4 items
[0]
asset:data:geo:GSE39582 not downloaded
[1]
asset:data:geo:GSE39582 licence not read
[2]
asset:data:geo:GSE41258 not downloaded
[3]
asset:data:geo:GSE41258 licence not read
analysis object · 4 fields
state
partial
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[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
In univariate and multivariate Cox regression analyses, our model was associated with survival (P = 0.002).
[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
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id
method-3
family
differential_expression
specific
limma_voom
label
Differential expression analysis
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[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
0.8
band
high
quote
limma
[3] object · 10 fields
id
method-4
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contingency_analysis
specific
chi_square
label
Categorical (contingency table) analysis
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[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
χ2
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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
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[0]
meta_analysis
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machine_learning
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survival_analysis
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statistical_regression
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pca
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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
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[0]
GSE41258
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GSE39582
resolved_accessions array · 2 items
[0]
GSE41258
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GSE39582
statements array · 1 item
[0]
The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.
basis
The paper names GSE41258, GSE39582 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 · 2 items
[0]
source:pmid:33557848
[1]
data:geo:GSE39582
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:GSE39582
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
2026-10-31T18:26:57Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
27741
completion_tokens
2810
cached_tokens
794
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:33557848
type
paper
label
pmid:33557848
[1] object · 3 fields
id
source:pmid:33557848
type
manuscript
label
PMID 33557848 full text
[2] object · 3 fields
id
data:geo:GSE39582
type
dataset
label
GEO GSE39582
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:33557848
type
paper
label
pmid:33557848
[1] object · 3 fields
id
source:pmid:33557848
type
manuscript
label
PMID 33557848 full text
[2] object · 3 fields
id
data:geo:GSE39582
type
dataset
label
GEO GSE39582
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-33557848
type
extraction
used array · 1 item
[0]
source:pmid:33557848
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE39582
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE39582
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:33557848
parent_hash
sha256:673bb4b003d1e979c1e6393decfc18589932faa7671b7e0c88ae0b4081f7cc8d
fork_of
null
gaps array · 9 items
[0]
asset:data:geo:GSE39582 licence not read
[1]
asset:data:geo:GSE39582 not downloaded
[2]
asset:data:geo:GSE41258 licence not read
[3]
asset:data:geo:GSE41258 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 · 3 items
[0] object · 11 fields
role
data_generation
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 4 items
[0]
tion-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays. Next
[1]
n-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays. Next
[2]
sed (Fig. 3b). The outcomes were verified by RT-qPCR. The mRNA levels of HOXC8 and MS4A2 in the 3
[3]
and normal adjacent tissues was detected by RT-qPCR. e–f Statistical analysis of the immunoreact
order_basis
paper_text_order:543
id
assay:1
[1] object · 11 fields
role
data_generation
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 4 items
[0]
tive polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays. Next, the correlation between
[1]
reaction (RT-qPCR) and immunohistochemistry (IHC) assays. Next, the correlation between the m
[2]
nding non-tumour tissues. g–h Representative immunohistochemical images of HOXC8 and MS4A2 expression in clin
[3]
by RT-qPCR. e–f Statistical analysis of the immunoreactivity score of HOXC8 and MS4A2 between 40 pairs of
order_basis
paper_text_order:556
id
assay:2
[2] 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]
In univariate and multivariate Cox regression analyses, our model was associated with survival (P = 0.002).
order_basis
consumes_earlier_output
id
assay:3
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33557848", "kind": "science-record", "revision": 7, "content_hash": "sha256:00b48e20372b7880de523e49573cefbddd6493500c3116ea80e492d84612e68c", "created_at": "2026-11-01T15:41:24Z", "updated_at": "2026-11-01T22:03:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a two-gene prognostic model associated with cytolytic activity for colon cancer.", "doi": "10.1186/s12935-021-01782-6", "pmid": "33557848", "authors": ["Xiaoye Jiang", "Zhongxiang Jiang", "Lichun Xiang", "Xuenuo Chen", "Jiao Wu", "Zheng Jiang"], "journal": "Cancer cell international", "year": 2021, "abstract": "BACKGROUND: Increasing evidence has shown that cytolytic activity (CYT) is a new immunotherapy biomarker that characterises the antitumour immune activity of cytotoxic T cells and macrophages. In this study, we established a prognostic model associated with CYT.\nMETHODS: A prognostic model based on CYT-related genes was developed. Furthermore, aberrant expression of genes of the model in colon cancer (CC) was identified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays. Next, the correlation between the model and T-cell infiltration in the CC microenvironment was analysed. The Tumour Immune Dysfunction and Exclusion (TIDE) algorithm and subclass mapping were used to predict clinical responses to immune checkpoint inhibitors.\nRESULTS: In total, 280 of the 1418 genes were differentially expressed based on CYT. A prognostic model (including HOXC8 and MS4A2) was developed based on CYT-related genes. The model was validated using the testing set, the whole set and a Gene Expression Omnibus (GEO) cohort (GSE41258). Gene set enrichment analysis (GSEA) and other analyses showed that the levels of immune infiltration and antitumour immune activation in low-risk-score tumours were greater than those in high-risk-score tumours. CC patients with a low-risk-score showed more promise in the response to anti-immune checkpoint therapy.\nCONCLUSIONS: Overall, our model may precisely predict the overall survival of CC and reflect the strength of antitumour immune activity in the CC microenvironment. Furthermore, the model may be a predictive factor for the response to immunotherapy.", "claims": [{"id": "claim-method", "statement": "In univariate and multivariate Cox regression analyses, our model was associated with survival (P = 0.002).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33557848", "locator": "sections[18] \"Relationship between the CYT-related prognostic model and clinicopathological features\" paragraph 3", "quote": "In univariate and multivariate Cox regression analyses, our model was associated with survival (P = 0.002)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33557848", "locator": "sections[31] \"notes\" paragraph 1", "quote": "The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations."}], "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:33557848"], "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:GSE39582"], "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:GSE39582"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33557848", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-021-01782-6", "sha256": "sha256:d618db0a2e285411af228730356d3e9581d215a3216aaeac2c1d802b7acbe4ed", "bytes": 36238, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12935-021-01782-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7869500", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE39582", "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=GSE39582", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE39582", "version": null, "note": "The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The obtained data were used according to the TCGA (https://portal.gdc.cancer.gov/repository), GTEx (http://commonfund.nih.gov/GTEx) and GEO (https://www.ncbi.nlm.nih.gov/geo/) data access policies. The mutation data, mRNA profile data and clinical feature data for CC are publicly obtainable and open access. All analyses were carried out based on pertinent guidelines and regulations.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1681353", "GSM1681354", "GSM1681355", "GSM1681356", "GSM1681357", "GSM1681358", "GSM1681359", "GSM1681360", "GSM1681361", "GSM1681362", "GSM1681363", "GSM1681364", "GSM1681365", "GSM1681366", "GSM1681367", "GSM1681368", "GSM1681369", "GSM1681370", "GSM1681371", "GSM971957", "GSM971958", "GSM971959", "GSM971960", "GSM971961", "GSM971962", "GSM971963", "GSM971964", "GSM971965", "GSM971966", "GSM971967", "GSM971968", "GSM971969", "GSM971970", "GSM971971", "GSM971972", "GSM971973", "GSM971974", "GSM971975", "GSM971976", "GSM971977", "GSM971978", "GSM971979", "GSM971980", "GSM971981", "GSM971982", "GSM971983", "GSM971984", "GSM971985", "GSM971986", "GSM971987", "GSM971988", "GSM971989", "GSM971990", "GSM971991", "GSM971992", "GSM971993", "GSM971994", "GSM971995", "GSM971996", "GSM971997", "GSM971998", "GSM971999", "GSM972000", 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Next", "n-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays. Next", "sed (Fig. 3b). The outcomes were verified by RT-qPCR. The mRNA levels of HOXC8 and MS4A2 in the 3", "and normal adjacent tissues was detected by RT-qPCR. e–f Statistical analysis of the immunoreact"], "order_basis": "paper_text_order:543", "id": "assay:1"}, {"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": ["tive polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC) assays. Next, the correlation between", "reaction (RT-qPCR) and immunohistochemistry (IHC) assays. 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