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pmid:30254489

Establishment and validation of a 7-microRNA prognostic signature for non-small cell lung cancer.

Nan Wang · Huihui Guo · Zhaohuo Dong · Qiuqiang Chen · Xilin Zhang · Weiyun Shen · Ying Bao · Xiang Wang

Cancer management and research · 2018 doi:10.2147/CMAR.S170481

Paper

complete

Experiment

partial

Data

partial

Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:30254489
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title
Establishment and validation of a 7-microRNA prognostic signature for non-small cell lung cancer.
doi
10.2147/CMAR.S170481
pmid
30254489
authors array · 8 items
[0]
Nan Wang
[1]
Huihui Guo
[2]
Zhaohuo Dong
[3]
Qiuqiang Chen
[4]
Xilin Zhang
[5]
Weiyun Shen
[6]
Ying Bao
[7]
Xiang Wang
journal
Cancer management and research
year
2018
abstract
PURPOSE: A series of microRNAs (miRNAs) have been identified as associated with the survival of patients with non-small-cell lung cancer (NSCLC). The aim of the present study was to explore whether combination of these experimentally validated individual miRNA biomarkers could be used to further increase their prognostic power in NSCLC. PATIENTS AND METHODS: Based on previously validated NSCLC prognostic miRNAs, gene signatures that could discriminate high-risk subgroups with poor clinical outcome in four NSCLC miRNA expression datasets (GSE13937, GSE16025, The Cancer Genome Atlas Lung Adenocarcinoma, and TCGA lung squamous cell carcinoma) were developed using the SurvMicro tool. The potential of the miRNA signature established was validated by quantitative real-time PCR analysis of clinical NSCLC samples, and its prognostic power evaluated using the survivalROC method. RESULTS: We developed two miRNA signatures with prognostic significance for NSCLC, comprising 12- and 7-miRNAs. The 7-miRNA signature (miR-148b, miR-365, miR-32, miR-375, miR-21, miR-125b, and miR-155) was a subset of a 12-miRNA set that retained prognostic power across NSCLC cohorts. Compared with previously established miRNA signatures, our 7-miRNA signature has similar potential, while comprising fewer miRNA components. The prognostic ability of the 7-miRNA signature was validated experimentally in an independent NSCLC cohort using real-time PCR (HR=3.4847, 95% CI=1.3693-8.8680, P=0.0092), and this signature, combined with tumor pathological stage, had superior prognostic ability compared with tumor stage alone. CONCLUSION: Our data indicate that the established 7-miRNA signature is simple, robust, and may have greater clinical prognostic utility for patients with NSCLC.
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Survival was compared between high- and low-risk groups using Kaplan–Meier survival curves and the log-rank test.
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Survival was compared between high- and low-risk groups using Kaplan–Meier survival curves and the log-rank test.
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Prognostic significance of 12- and 7-miRNA signatures in four independent NSCLC cohorts
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Multivariate Cox regression analysis of 7-miRNA signature risk score and clinicopathological factors with overall survival
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Multivariate Cox regression analysis of 7-miRNA signature risk score and clinicopathological factors with overall survival
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NSCLC miRNA expression profiles datasets used in our analysis
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NSCLC miRNA expression profiles datasets used in our analysis
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caption
Primers for the signature miRNAs assays by real-time PCR
rows array · 25 items
[0] array · 3 items
[0]
miRNA
[1]
Primer
[2]
Primer sequence
[1] array · 3 items
[0]
hsa-miR-32
[1]
RT
[2]
5′-GTCGTATCCAGTGCAGGGTCCGAGGTATTCGACTGGATACGACTGCAACTT-3′
[2] array · 2 items
[0]
Forward
[1]
5′-GTGCAGGGTCCGAGGTATT-3′
[3] array · 2 items
[0]
Reverse
[1]
5′-GCCGCTATTGCACATTACTAAGTT-3′
[4] array · 3 items
[0]
hsa-miR-21
[1]
RT
[2]
5′-GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACTCAACA-3′
[5] array · 2 items
[0]
Forward
[1]
5′-GCCCGCTAGCTTATCAGACTGATG-3′
[6] array · 2 items
[0]
Reverse
[1]
5′-GTGCAGGGTCCGAGGT-3′
[7] array · 3 items
[0]
hsa-miR-125b
[1]
RT
[2]
5′-GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACTCACAAG-3′
[8] array · 2 items
[0]
Forward
[1]
5′-GCGGCTCCCTGAGACCCTAAC-3′
[9] array · 2 items
[0]
Reverse
[1]
5′-GTGCAGGGTCCGAGGT-3′
[10] array · 3 items
[0]
hsa-miR-155
[1]
RT
[2]
5′-GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACCCCCTA-3′
[11] array · 2 items
[0]
Forward
[1]
5′-CTCGTGGTAATGCTAATTGTGA-3′
[12] array · 2 items
[0]
Reverse
[1]
5′-GTGCAGGGTCCGAGGT-3′
[13] array · 3 items
[0]
hsa-mir-148b
[1]
RT
[2]
5′-GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACGCCTGA-3′
[14] array · 2 items
[0]
Forward
[1]
5′-GGCGCAAGTTCTGTTATACAC-3′
[15] array · 2 items
[0]
Reverse
[1]
5′-GTGCAGGGTCCGAGGT-3′
[16] array · 3 items
[0]
hsa-miR-365
[1]
RT
[2]
5′-GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACATAAGG-3′
[17] array · 2 items
[0]
Forward
[1]
5′-CGTAATGCCCCTAAAAAT-3′
[18] array · 2 items
[0]
Reverse
[1]
5′-AGCCGTTTGTTCGTTCGGCT-3′
[19] array · 3 items
[0]
hsa-miR-367
[1]
RT
[2]
5′-GTCGTATCCAGTGCAGGGTCCGAGGTATTCGCACTGGATACGACTCACGC-3′
[20] array · 2 items
[0]
Forward
[1]
5′-AGCCGTTTGTTCGTTCGGCT-3′
[21] array · 2 items
[0]
Reverse
[1]
5′-GTGCAGGGTCCGAGGT-3′
[22] array · 3 items
[0]
U6 snRNA
[1]
RT
[2]
5′-CGCTTCACGAATTTGCGTGTCAT-3′
[23] array · 2 items
[0]
Forward
[1]
5′-GCTTCGGCAGCACATATACTAAAAT-3′
[24] array · 2 items
[0]
Reverse
[1]
5′-CGCTTCACGAATTTGCGTGTCAT-3′
locator
section[21]/table-wrap[2]#db_ds_table-wrap2_reqid_
gaps array · 0 items
analysis object · 4 fields
state
complete
methods array · 1 item
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
log_rank_test
label
Survival analysis
dsl_operations array · 1 item
[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
1
band
verbatim
quote
Survival was compared between high- and low-risk groups using Kaplan–Meier survival curves and the log-rank test.
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
blocked
tier
R4
blocked_on
data:accession_absent
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
logrank_test
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: log_rank_test.
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
R4
reachable
false
accessions array · 0 items
resolved_accessions array · 0 items
statements array · 0 items
basis
The paper names no accession to its source data, so the data has to come from the authors.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
logrank_test
assets array · 9 items
[0]
source:pmid:30254489
[1]
asset:table:pmid:30254489:1
[2]
asset:table:pmid:30254489:2
[3]
asset:table:pmid:30254489:3
[4]
asset:table:pmid:30254489:4
[5]
asset:table:pmid:30254489:5
[6]
asset:table:pmid:30254489:6
[7]
asset:table:pmid:30254489:7
[8]
asset:table:pmid:30254489:8
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:None
gaps array · 1 item
[0]
data:accession_absent
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
2026-10-31T18:36:28Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
null
calls
3
usage object · 3 fields
prompt_tokens
22138
completion_tokens
2524
cached_tokens
648
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:30254489
type
paper
label
pmid:30254489
[1] object · 3 fields
id
source:pmid:30254489
type
manuscript
label
PMID 30254489 full text
[2] object · 3 fields
id
data:geo:None
type
dataset
label
GEO None
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:30254489
type
paper
label
pmid:30254489
[1] object · 3 fields
id
source:pmid:30254489
type
manuscript
label
PMID 30254489 full text
[2] object · 3 fields
id
data:geo:None
type
dataset
label
GEO None
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-30254489
type
extraction
used array · 1 item
[0]
source:pmid:30254489
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-None
type
accession_resolution
used array · 1 item
[0]
data:geo:None
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:30254489
parent_hash
sha256:90dbdcc00ac137a2ee94cb0097bc23568bc0a63a44e24d8c7d30fc931c2b2594
fork_of
null
gaps array · 5 items
[0]
execution.not_run
[1]
review.human_critique
[2]
review.independent_reader
[3]
review.machine_critique
[4]
step:obtain_source_data blocked on data:accession_absent
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_id
clinical_cohort
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 2 items
[0]
dentified as associated with the survival of patients with non-small-cell lung cancer (NSCLC). The aim
[1]
have greater clinical prognostic utility for patients with NSCLC.
order_basis
paper_text_order:149
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 · 3 items
[0]
re established was validated by quantitative real-time PCR analysis of clinical NSCLC samples, and its
[1]
entally in an independent NSCLC cohort using real-time PCR (HR=3.4847, 95% CI=1.3693-8.8680, P=0.0092),
[2]
of the 7-miRNA signature using quantitative real-time PCR. The samples were collected from archived tu
order_basis
paper_text_order:821
id
assay:2
[2] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
logrank_test
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Survival was compared between high- and low-risk groups using Kaplan–Meier survival curves and the log-rank test.
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:30254489", "kind": "science-record", "revision": 6, "content_hash": "sha256:b108e94ba4535a0de6c946759bc0666e114e873c2c54fdba1e6746ae9ea4f32f", "created_at": "2026-11-01T15:40:37Z", "updated_at": "2026-11-01T21:21:40Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Establishment and validation of a 7-microRNA prognostic signature for non-small cell lung cancer.", "doi": "10.2147/CMAR.S170481", "pmid": "30254489", "authors": ["Nan Wang", "Huihui Guo", "Zhaohuo Dong", "Qiuqiang Chen", "Xilin Zhang", "Weiyun Shen", "Ying Bao", "Xiang Wang"], "journal": "Cancer management and research", "year": 2018, "abstract": "PURPOSE: A series of microRNAs (miRNAs) have been identified as associated with the survival of patients with non-small-cell lung cancer (NSCLC). The aim of the present study was to explore whether combination of these experimentally validated individual miRNA biomarkers could be used to further increase their prognostic power in NSCLC.\nPATIENTS AND METHODS: Based on previously validated NSCLC prognostic miRNAs, gene signatures that could discriminate high-risk subgroups with poor clinical outcome in four NSCLC miRNA expression datasets (GSE13937, GSE16025, The Cancer Genome Atlas Lung Adenocarcinoma, and TCGA lung squamous cell carcinoma) were developed using the SurvMicro tool. The potential of the miRNA signature established was validated by quantitative real-time PCR analysis of clinical NSCLC samples, and its prognostic power evaluated using the survivalROC method.\nRESULTS: We developed two miRNA signatures with prognostic significance for NSCLC, comprising 12- and 7-miRNAs. The 7-miRNA signature (miR-148b, miR-365, miR-32, miR-375, miR-21, miR-125b, and miR-155) was a subset of a 12-miRNA set that retained prognostic power across NSCLC cohorts. Compared with previously established miRNA signatures, our 7-miRNA signature has similar potential, while comprising fewer miRNA components. The prognostic ability of the 7-miRNA signature was validated experimentally in an independent NSCLC cohort using real-time PCR (HR=3.4847, 95% CI=1.3693-8.8680, P=0.0092), and this signature, combined with tumor pathological stage, had superior prognostic ability compared with tumor stage alone.\nCONCLUSION: Our data indicate that the established 7-miRNA signature is simple, robust, and may have greater clinical prognostic utility for patients with NSCLC.", "claims": [{"id": "claim-method", "statement": "Survival was compared between high- and low-risk groups using Kaplan–Meier survival curves and the log-rank test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30254489", "locator": "sections[9] \"Statistics\" paragraph 2", "quote": "Survival was compared between high- and low-risk groups using Kaplan–Meier survival curves and the log-rank test."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "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:30254489"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30254489", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/CMAR.S170481", "sha256": "sha256:b493a8e3cbf01c55b6e1c55e8621ea43c2333f556ad582872d0e16de52d942d3", "bytes": 25479, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/CMAR.S170481", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6140736", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "asset:table:pmid:30254489:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:cabf619b7ddd3597e0f116ef0104ffab6ca73e5f33f2a632cb093ee9434e9936", "bytes": 777, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#t1-cmar-10-3463", "version": null, "note": "Prognostic significance of 12- and 7-miRNA signatures in four independent NSCLC cohorts", "structure": {"pmcid": "PMC6140736", "section_index": 10, "section_title": "Results", "row_count": 6, "column_count": 7}, "table": {"label": "Table 1", "caption": "Prognostic significance of 12- and 7-miRNA signatures in four independent NSCLC cohorts", "rows": [["Dataset", "12-miRNA signature", "7-miRNA signature"], ["Concordance index", "HR (95% CI)", "P-value", "Concordance index", "HR (95% CI)", "P-value"], ["Mathe Zhao lung GSE13937", "64.05", "2.32 (1.38–3.9)", "0.0014", "64.82", "2.6 (1.52–4.45)", "0.00027"], ["Raponi Beer lung GSE16025", "69.85", "2.49 (1.21–5/13)", "0.013", "63.76", "3.13 (1.52–6.42)", "0.0019"], ["TCGA LUAD", "63.98", "2.78 (1.58–4.9)", "0.0004", "67.71", "2.82 (1.57–5.05)", "0.00049"], ["TCGA LUSC", "59.89", "1.70 (0.95–3.04)", "0.071", "60.17", "2.1 (1.2–3.69)", "0.0097"]], "row_count": 6, "column_count": 7, "numeric_cells": 30, "header_rows": 2, "locator": "section[10]/table-wrap[1]#t1-cmar-10-3463"}}, {"id": "asset:table:pmid:30254489:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:6573547fbeb23dd46ccaa49fbff6a6575031e4b872e328f7c28103fd333ee489", "bytes": 667, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[2]#t2-cmar-10-3463", "version": null, "note": "Comparison of our 7-miRNA signature with two other miRNA signatures in NSCLC", "structure": {"pmcid": "PMC6140736", "section_index": 10, "section_title": "Results", "row_count": 6, "column_count": 7}, "table": {"label": "Table 2", "caption": "Comparison of our 7-miRNA signature with two other miRNA signatures in NSCLC", "rows": [["Dataset", "7-miRNA signature", "Raponi signature", "Yu signature"], ["Concordance index", "P-value", "Concordance index", "P-value", "Concordance index", "P-value"], ["Mathe Zhao", "64.82", "0.00027", "74.76", "1.063e-06", "59.75", "0.052"], ["Raponi Beer", "63.76", "0.0019", "77.56", "0.00016", "59.68", "0.1621"], ["TCGA LUAD", "67.71", "0.00049", "73.56", "8.741e-06", "58.36", "0.1149"], ["TCGA LUSC", "60.17", "0.0097", "63.63", "0.00086", "63.04", "0.1089"]], "row_count": 6, "column_count": 7, "numeric_cells": 25, "header_rows": 2, "locator": "section[10]/table-wrap[2]#t2-cmar-10-3463"}}, {"id": "asset:table:pmid:30254489:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:b592e8f9d15b6cc33cc5c2418d5c1fb54b1e1ba17c043ed5b5997a83deaa8bb0", "bytes": 869, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[3]#t3-cmar-10-3463", "version": null, "note": "Association between miRNA signature risk with clinicopathological characteristics", "structure": {"pmcid": "PMC6140736", "section_index": 10, "section_title": "Results", "row_count": 21, "column_count": 4}, "table": {"label": "Table 3", "caption": "Association between miRNA signature risk with clinicopathological characteristics", "rows": [["Characteristics", "7-miRNA signature", "P-value"], ["High-risk(n=20)", "Low-risk(n=20)"], ["Age (years)", "", "", ""], ["<60 (n=20)", "7", "13", "0.1138"], ["≥60 (n=20)", "13", "7", ""], ["Gender", "", "", ""], ["Male (n=36)", "20", "16", "0.1138"], ["Female (n=4)", "0", "4", ""], ["Histology", "", "", ""], ["LUAD (n=17)", "10", "7", "0.5524"], ["LUSC (n=23)", "10", "13", ""], ["Tumor size", "", "", ""], ["T1–2 (n=30)", "14", "16", "0.7150"], ["T3–4 (n=10)", "6", "4", ""], ["Lymph node metastasis", "", "", ""], ["N0 (n=23)", "11", "12", "1.000"], ["N1 (n=17)", "9", "8", ""], ["Stage", "", "", ""], ["I (n=18)", "8", "10", ""], ["II (n=10)", "4", "6", "0.3761"], ["III (n=12)", "8", "4", ""]], "row_count": 21, "column_count": 4, "numeric_cells": 48, "header_rows": 2, "locator": "section[10]/table-wrap[3]#t3-cmar-10-3463"}}, {"id": "asset:table:pmid:30254489:4", "role": "table", "format": "jats-table", "media_type": 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