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pmid:35096060

Identification of Biomarkers Associated with Cancerous Change in Oral Leukoplakia Based on Integrated Transcriptome Analysis.

Chunshen Li · Yingying Shi · Lihua Zuo · Mingzhe Xin · Xiaomeng Guo · Jianli Sun · Shuai Chen · Bin Zhao · Zhe Yang · Zhi Sun · Hongyu Zhao

Journal of oncology · 2022 doi:10.1155/2022/4599305

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complete

Experiment

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Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:35096060
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science-record
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2026-11-01T17:36:49Z
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2026-11-01T21:27:05Z
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title
Identification of Biomarkers Associated with Cancerous Change in Oral Leukoplakia Based on Integrated Transcriptome Analysis.
doi
10.1155/2022/4599305
pmid
35096060
authors array · 11 items
[0]
Chunshen Li
[1]
Yingying Shi
[2]
Lihua Zuo
[3]
Mingzhe Xin
[4]
Xiaomeng Guo
[5]
Jianli Sun
[6]
Shuai Chen
[7]
Bin Zhao
[8]
Zhe Yang
[9]
Zhi Sun
[10]
Hongyu Zhao
journal
Journal of oncology
year
2022
abstract
OBJECTIVE: Oral leukoplakia (OLK) is the most common precancerous lesion in the oral cavity. This study aimed to explore key biomarkers for monitoring OLK for early diagnosis of oral squamous cell carcinoma (OSCC) and screen small-molecule drugs for the prevention of OSCC. METHOD: The Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, namely, GSE85195 and GSE25099. The data of the normal group, OLK group, and OSCC group were analyzed by weighted gene coexpression network analysis (WGCNA) to identify the most significant gene module and differentially expressed genes (DEGs). The intersection genes were extracted as the key genes of OLK carcinogenesis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed in the module. Connectivity Map and molecular docking were used to screen small-molecule drugs. The diagnostic values of four key genes were identified and verified in the GSE26549 dataset. RESULTS: WGCNA obtained the red module (r = -0.91, p < 0.05) with the strongest correlation with cancerous phenotype. GO enrichment analysis showed 60 pathways, including 28 biological processes, 11 cell components, and 21 molecular functions, and KEGG enrichment analysis showed 4 pathways (p < 0.05). In the differential expression analysis, there was no intersection between the upregulated genes and the red module genes. However, the intersection of the downregulated genes and the red module genes yielded 4 key genes: dopachrome tautomerase (DCT), keratin 3 (KRT3), keratin 76 (KRT76), and FAM3 metabolic regulation signal molecule B (FAM3B). The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913-1.000). The sensitivity was 0.933, and the specificity was 0.923. The diagnostic model was successfully verified in GSE26549 (AUC = 0.745, CI = 0.638-0.851). Compared with the diagnostic models of the previous studies, the diagnostic efficiency of this model was the highest. The small-molecule drugs, selumetinib and benidipine, were selected according to the gene expression profile and showed binding activity when docking with the above molecules. CONCLUSIONS: This study provides new targets and drugs for OLK. These targets could be used as the key diagnostic molecules for long-term follow-up of OLK. The small-molecule drugs selumetinib and benidipine could be used for the prevention and treatment of OSCC.
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WGCNA package [15] was used to perform weighted gene coexpression network analysis
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sections[4] "2.2. Weighted Gene Coexpression Network Analysis (WGCNA)" paragraph 2
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WGCNA package [15] was used to perform weighted gene coexpression network analysis
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The data that support the findings of this study are openly available in GSE85195, GSE25099, and GSE26549 at https://www.ncbi.nlm.nih.gov/geo/.
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The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913–1.000).
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The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913–1.000).
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Expression data from 57 patients with oral cancer and 22 normal persons
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Gene Expression Profiling Predicts the Development of Oral Cancer
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Gene Expression analysis of Oral Leukoplakia and Early Stage Oral Squamous Cell Carcinoma
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data:geo:GSE25099
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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:35096060
parent_hash
sha256:162f8fc187de57faa0d1e1cc3736ce94dfd3358aedf7ecad75ed06825318a67e
fork_of
null
gaps array · 11 items
[0]
asset:data:geo:GSE25099 licence not read
[1]
asset:data:geo:GSE25099 not downloaded
[2]
asset:data:geo:GSE26549 licence not read
[3]
asset:data:geo:GSE26549 not downloaded
[4]
asset:data:geo:GSE85195 licence not read
[5]
asset:data:geo:GSE85195 not downloaded
[6]
execution.not_run
[7]
method.reader_named_unmapped
[8]
review.human_critique
[9]
review.independent_reader
[10]
review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_id
microarray
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
s (GEO) database was explored to extract two microarray datasets, namely, GSE85195 and GSE25099. The
order_basis
paper_text_order:434
id
assay:1
[1] object · 11 fields
role
analysis
definition_id
network_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
pathway_enrich
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
GO enrichment
order_basis
consumes_earlier_output
id
assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35096060", "kind": "science-record", "revision": 4, "content_hash": "sha256:6240db01d253ebea92dd70fb20312b51a7195caf8ef29c1866af7c1b8a6b6928", "created_at": "2026-11-01T17:36:49Z", "updated_at": "2026-11-01T21:27:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Biomarkers Associated with Cancerous Change in Oral Leukoplakia Based on Integrated Transcriptome Analysis.", "doi": "10.1155/2022/4599305", "pmid": "35096060", "authors": ["Chunshen Li", "Yingying Shi", "Lihua Zuo", "Mingzhe Xin", "Xiaomeng Guo", "Jianli Sun", "Shuai Chen", "Bin Zhao", "Zhe Yang", "Zhi Sun", "Hongyu Zhao"], "journal": "Journal of oncology", "year": 2022, "abstract": "OBJECTIVE: Oral leukoplakia (OLK) is the most common precancerous lesion in the oral cavity. This study aimed to explore key biomarkers for monitoring OLK for early diagnosis of oral squamous cell carcinoma (OSCC) and screen small-molecule drugs for the prevention of OSCC.\nMETHOD: The Gene Expression Omnibus (GEO) database was explored to extract two microarray datasets, namely, GSE85195 and GSE25099. The data of the normal group, OLK group, and OSCC group were analyzed by weighted gene coexpression network analysis (WGCNA) to identify the most significant gene module and differentially expressed genes (DEGs). The intersection genes were extracted as the key genes of OLK carcinogenesis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed in the module. Connectivity Map and molecular docking were used to screen small-molecule drugs. The diagnostic values of four key genes were identified and verified in the GSE26549 dataset.\nRESULTS: WGCNA obtained the red module (r = -0.91, p < 0.05) with the strongest correlation with cancerous phenotype. GO enrichment analysis showed 60 pathways, including 28 biological processes, 11 cell components, and 21 molecular functions, and KEGG enrichment analysis showed 4 pathways (p < 0.05). In the differential expression analysis, there was no intersection between the upregulated genes and the red module genes. However, the intersection of the downregulated genes and the red module genes yielded 4 key genes: dopachrome tautomerase (DCT), keratin 3 (KRT3), keratin 76 (KRT76), and FAM3 metabolic regulation signal molecule B (FAM3B). The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913-1.000). The sensitivity was 0.933, and the specificity was 0.923. The diagnostic model was successfully verified in GSE26549 (AUC = 0.745, CI = 0.638-0.851). Compared with the diagnostic models of the previous studies, the diagnostic efficiency of this model was the highest. The small-molecule drugs, selumetinib and benidipine, were selected according to the gene expression profile and showed binding activity when docking with the above molecules.\nCONCLUSIONS: This study provides new targets and drugs for OLK. These targets could be used as the key diagnostic molecules for long-term follow-up of OLK. The small-molecule drugs selumetinib and benidipine could be used for the prevention and treatment of OSCC.", "claims": [{"id": "claim-method", "statement": "WGCNA package [15] was used to perform weighted gene coexpression network analysis", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35096060", "locator": "sections[4] \"2.2. Weighted Gene Coexpression Network Analysis (WGCNA)\" paragraph 2", "quote": "WGCNA package [15] was used to perform weighted gene coexpression network analysis"}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are openly available in GSE85195, GSE25099, and GSE26549 at https://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35096060", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "The data that support the findings of this study are openly available in GSE85195, GSE25099, and GSE26549 at https://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913–1.000).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35096060", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913–1.000)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The area under the curve of the diagnostic model constructed by these four genes was 0.963 (CI = 0.913–1.000).", "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:35096060"], "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:GSE25099"], "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:GSE25099"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35096060", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/4599305", "sha256": 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