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pmid:33980221

Low expression of CHRDL1 and SPARCL1 predicts poor prognosis of lung adenocarcinoma based on comprehensive analysis and immunohistochemical validation.

Huan Deng · Qingqing Hang · Dijian Shen · Yibi Zhang · Ming Chen

Cancer cell international · 2021 doi:10.1186/s12935-021-01933-9

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Experiment

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Data

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pmid:33980221
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2026-11-01T15:41:35Z
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title
Low expression of CHRDL1 and SPARCL1 predicts poor prognosis of lung adenocarcinoma based on comprehensive analysis and immunohistochemical validation.
doi
10.1186/s12935-021-01933-9
pmid
33980221
authors array · 5 items
[0]
Huan Deng
[1]
Qingqing Hang
[2]
Dijian Shen
[3]
Yibi Zhang
[4]
Ming Chen
journal
Cancer cell international
year
2021
abstract
PURPOSE: Exploring the molecular mechanisms of lung adenocarcinoma (LUAD) is beneficial for developing new therapeutic strategies and predicting prognosis. This study was performed to select core genes related to LUAD and to analyze their prognostic value. METHODS: Microarray datasets from the GEO (GSE75037) and TCGA-LUAD datasets were analyzed to identify differentially coexpressed genes in LUAD using weighted gene coexpression network analysis (WGCNA) and differential gene expression analysis. Functional enrichment analysis was conducted, and a protein-protein interaction (PPI) network was established. Subsequently, hub genes were identified using the CytoHubba plug-in. Overall survival (OS) analyses of hub genes were performed. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (THPA) databases were used to validate our findings. Gene set enrichment analysis (GSEA) of survival-related hub genes were conducted. Immunohistochemistry (IHC) was carried out to validate our findings. RESULTS: We identified 486 differentially coexpressed genes. Functional enrichment analysis suggested these genes were primarily enriched in the regulation of epithelial cell proliferation, collagen-containing extracellular matrix, transforming growth factor beta binding, and signaling pathways regulating the pluripotency of stem cells. Ten hub genes were detected using the maximal clique centrality (MCC) algorithm, and four genes were closely associated with OS. The CPTAC and THPA databases revealed that CHRDL1 and SPARCL1 were downregulated at the mRNA and protein expression levels in LUAD, whereas SPP1 was upregulated. GSEA demonstrated that DNA-dependent DNA replication and catalytic activity acting on RNA were correlated with CHRDL1 and SPARCL1 expression, respectively. The IHC results suggested that CHRDL1 and SPARCL1 were significantly downregulated in LUAD. CONCLUSIONS: Our study revealed that survival-related hub genes closely correlated with the initiation and progression of LUAD. Furthermore, CHRDL1 and SPARCL1 are potential therapeutic and prognostic indicators of LUAD.
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To explore the prognostic values of hub genes in LUAD, Kaplan–Meier univariate survival analysis was conducted through the survival package.
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To explore the prognostic values of hub genes in LUAD, Kaplan–Meier univariate survival analysis was conducted through the survival package.
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The datasets downloaded and analyzed during the current study are available on the TCGA and GEO database: TCGA-LUAD database: https://portal.gdc.cancer.gov/; GSE75037: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75037; GSE19188: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19188.
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The datasets downloaded and analyzed during the current study are available on the TCGA and GEO database: TCGA-LUAD database: https://portal.gdc.cancer.gov/; GSE75037: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75037; GSE19188: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19188.
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External validation of public databases
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[10]
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[11]
None
[12]
None
[4] array · 13 items
[0]
SPARCL1
[1]
Not detected
[2]
Weak
[3]
< 25%
[4]
Cytoplasmic/membranous
[5]
Not detected
[6]
Negative
[7]
None
[8]
None
[9]
Not detected
[10]
Negative
[11]
None
[12]
None
[5] array · 13 items
[0]
SPP1
[1]
Low
[2]
Weak
[3]
75–25%
[4]
Cytoplasmic/membranous
[5]
Not detected
[6]
Negative
[7]
None
[8]
None
[9]
Not detected
[10]
Negative
[11]
None
[12]
None
[6] array · 13 items
[0]
PENK
[1]
Low
[2]
Weak
[3]
> 75%
[4]
Cytoplasmic/membranous
[5]
Not detected
[6]
Negative
[7]
None
[8]
None
[9]
Not detected
[10]
Negative
[11]
None
[12]
None
locator
section[18]/table-wrap[2]#Tab2
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note
Relative pathways associated with the expression of CHRDL1 and SPARCL1 using GSEA
structure object · 5 fields
pmcid
PMC8117659
section_index
19
section_title
GSEA of survival-related hub genes
row_count
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column_count
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table object · 8 fields
label
Table 3
caption
Relative pathways associated with the expression of CHRDL1 and SPARCL1 using GSEA
rows array · 21 items
[0] array · 6 items
[0]
Gene
[1]
Name
[2]
ES
[3]
NES
[4]
NOMp-value
[5]
FDRq-value
[1] array · 6 items
[0]
CHRDL1
[1]
GO_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR
[2]
− 0.55
[3]
− 1.93
[4]
< 0.0001
[5]
0.109
[2] array · 5 items
[0]
GO_CELL_CYCLE_CHECKPOINT
[1]
− 0.51
[2]
− 1.93
[3]
0.006
[4]
0.107
[3] array · 5 items
[0]
GO_DNA_UNWINDING_INVOLVED_IN_DNA_REPLICATION
[1]
− 0.81
[2]
− 1.93
[3]
< 0.0001
[4]
0.106
[4] array · 5 items
[0]
GO_EXONUCLEASE_ACTIVITY
[1]
− 0.53
[2]
− 1.92
[3]
0.002
[4]
0.116
[5] array · 5 items
[0]
GO_RNA_SPLICING_VIA_TRANSESTERIFICATION_REACTIONS
[1]
− 0.53
[2]
− 1.92
[3]
0.006
[4]
0.114
[6] array · 5 items
[0]
GO_TELOMERE_ORGANIZATION
[1]
− 0.54
[2]
− 1.91
[3]
0.002
[4]
0.114
[7] array · 5 items
[0]
GO_ATTACHMENT_OF_SPINDLE_MICROTUBULES_TO_KINETOCHORE
[1]
− 0.71
[2]
− 1.91
[3]
< 0.0001
[4]
0.114
[8] array · 5 items
[0]
GO_MITOCHONDRIAL_MEMBRANE_ORGANIZATION
[1]
− 0.56
[2]
− 1.91
[3]
0.002
[4]
0.113
[9] array · 5 items
[0]
GO_MRNA_CLEAVAGE_AND_POLYADENYLATION_SPECIFICITY_FACTOR_COMPLEX
[1]
− 0.73
[2]
− 1.91
[3]
0.002
[4]
0.112
[10] array · 5 items
[0]
GO_DNA_BIOSYNTHETIC_PROCESS
[1]
− 0.47
[2]
− 1.91
[3]
0.002
[4]
0.112
[11] array · 6 items
[0]
SPARCL1
[1]
GO_ENDONUCLEASE_COMPLEX
[2]
− 0.68
[3]
− 2.17
[4]
< 0.0001
[5]
0.047
[12] array · 5 items
[0]
GO_BASE_EXCISION_REPAIR
[1]
− 0.67
[2]
− 2.11
[3]
0.002
[4]
0.048
[13] array · 5 items
[0]
GO_SPLICEOSOMAL_COMPLEX
[1]
− 0.6
[2]
− 2.1
[3]
< 0.0001
[4]
0.031
[14] array · 5 items
[0]
GO_NCRNA_METABOLIC_PROCESS
[1]
− 0.59
[2]
− 2.1
[3]
< 0.0001
[4]
0.048
[15] array · 5 items
[0]
GO_MITOTIC_SPINDLE_ORGANIZATION
[1]
− 0.61
[2]
− 2.09
[3]
< 0.0001
[4]
0.048
[16] array · 5 items
[0]
GO_GLOMERULUS_DEVELOPMENT
[1]
0.69
[2]
2.27
[3]
< 0.0001
[4]
0.046
[17] array · 5 items
[0]
HP_HEMOPTYSIS
[1]
0.69
[2]
2.17
[3]
< 0.0001
[4]
0.033
[18] array · 5 items
[0]
GO_EXTERNAL_SIDE_OF_PLASMA_MEMBRANE
[1]
0.58
[2]
2.16
[3]
< 0.0001
[4]
0.048
[19] array · 5 items
[0]
GO_ENDOCARDIAL_CUSHION_DEVELOPMENT
[1]
0.68
[2]
2.16
[3]
< 0.0001
[4]
0.047
[20] array · 5 items
[0]
GO_POSITIVE_REGULATION_OF_PHOSPHATIDYLINOSITOL_3_KINASE_SIGNALING
[1]
0.6
[2]
2.16
[3]
< 0.0001
[4]
0.047
locator
section[19]/table-wrap[1]#Tab3
gaps array · 2 items
[0]
asset:data:geo:GSE75037 not downloaded
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asset:data:geo:GSE75037 licence not read
analysis object · 4 fields
state
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methods array · 3 items
[0] object · 10 fields
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method-1
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network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
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build_graph
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centrality_scores
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pathway_enrich
missing_operations array · 0 items
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edge_list
evidence object · 3 fields
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quote
protein-protein interaction
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id
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Network / pathway analysis
dsl_operations array · 3 items
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build_graph
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centrality_scores
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pathway_enrich
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edge_list
evidence object · 3 fields
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id
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null
specific
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Kaplan–Meier univariate survival analysis
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evidence object · 3 fields
score
1
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verbatim
quote
To explore the prognostic values of hub genes in LUAD, Kaplan–Meier univariate survival analysis was conducted through the survival package.
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gaps array · 1 item
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method.reader_named_unmapped
capability object · 3 fields
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assay_families array · 9 items
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meta_analysis
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survival_analysis
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statistical_regression
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pca
[5]
molecular_docking
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differential_expression
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gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
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blocked_on
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build_graph
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centrality_scores
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pathway_enrich
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network.
capability object · 4 fields
tier
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capability_id
capability:computational_analysis
availability_state
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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
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true
accessions array · 1 item
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GSE75037
resolved_accessions array · 1 item
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GSE75037
statements array · 1 item
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The datasets downloaded and analyzed during the current study are available on the TCGA and GEO database: TCGA-LUAD database: https://portal.gdc.cancer.gov/; GSE75037: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75037; GSE19188: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19188.
basis
The paper names GSE75037 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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asset:table:pmid:33980221:3
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run_analysis
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minimax
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[0]
arcinoma based on comprehensive analysis and immunohistochemical validation.
[1]
f survival-related hub genes were conducted. Immunohistochemistry (IHC) was carried out to validate our findin
[2]
genes were conducted. Immunohistochemistry (IHC) was carried out to validate our findings. R
[3]
L1 and SPARCL1 expression, respectively. The IHC results suggested that CHRDL1 and SPARCL1 we
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to analyze their prognostic value. METHODS: Microarray datasets from the GEO (GSE75037) and TCGA-LU
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33980221", "kind": "science-record", "revision": 5, "content_hash": "sha256:0cf8346b929d3fe2447134afeb89ac35dde6d265eba6ca4d3b089f4818256f71", "created_at": "2026-11-01T15:41:35Z", "updated_at": "2026-11-01T22:03:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Low expression of CHRDL1 and SPARCL1 predicts poor prognosis of lung adenocarcinoma based on comprehensive analysis and immunohistochemical validation.", "doi": "10.1186/s12935-021-01933-9", "pmid": "33980221", "authors": ["Huan Deng", "Qingqing Hang", "Dijian Shen", "Yibi Zhang", "Ming Chen"], "journal": "Cancer cell international", "year": 2021, "abstract": "PURPOSE: Exploring the molecular mechanisms of lung adenocarcinoma (LUAD) is beneficial for developing new therapeutic strategies and predicting prognosis. This study was performed to select core genes related to LUAD and to analyze their prognostic value.\nMETHODS: Microarray datasets from the GEO (GSE75037) and TCGA-LUAD datasets were analyzed to identify differentially coexpressed genes in LUAD using weighted gene coexpression network analysis (WGCNA) and differential gene expression analysis. Functional enrichment analysis was conducted, and a protein-protein interaction (PPI) network was established. Subsequently, hub genes were identified using the CytoHubba plug-in. Overall survival (OS) analyses of hub genes were performed. The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (THPA) databases were used to validate our findings. Gene set enrichment analysis (GSEA) of survival-related hub genes were conducted. Immunohistochemistry (IHC) was carried out to validate our findings.\nRESULTS: We identified 486 differentially coexpressed genes. Functional enrichment analysis suggested these genes were primarily enriched in the regulation of epithelial cell proliferation, collagen-containing extracellular matrix, transforming growth factor beta binding, and signaling pathways regulating the pluripotency of stem cells. Ten hub genes were detected using the maximal clique centrality (MCC) algorithm, and four genes were closely associated with OS. The CPTAC and THPA databases revealed that CHRDL1 and SPARCL1 were downregulated at the mRNA and protein expression levels in LUAD, whereas SPP1 was upregulated. GSEA demonstrated that DNA-dependent DNA replication and catalytic activity acting on RNA were correlated with CHRDL1 and SPARCL1 expression, respectively. The IHC results suggested that CHRDL1 and SPARCL1 were significantly downregulated in LUAD.\nCONCLUSIONS: Our study revealed that survival-related hub genes closely correlated with the initiation and progression of LUAD. Furthermore, CHRDL1 and SPARCL1 are potential therapeutic and prognostic indicators of LUAD.", "claims": [{"id": "claim-method", "statement": "To explore the prognostic values of hub genes in LUAD, Kaplan–Meier univariate survival analysis was conducted through the survival package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33980221", "locator": "sections[8] \"Prognostic roles and relationship with pathological stages of hub genes\" paragraph 2", "quote": "To explore the prognostic values of hub genes in LUAD, Kaplan–Meier univariate survival analysis was conducted through the survival package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets downloaded and analyzed during the current study are available on the TCGA and GEO database: TCGA-LUAD database: https://portal.gdc.cancer.gov/; GSE75037: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75037; GSE19188: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19188.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33980221", "locator": "sections[30] \"notes\" paragraph 1", "quote": "The datasets downloaded and analyzed during the current study are available on the TCGA and GEO database: TCGA-LUAD database: https://portal.gdc.cancer.gov/; GSE75037: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE75037; GSE19188: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE19188."}], "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:33980221"], "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:GSE75037"], "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:GSE75037"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33980221", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12935-021-01933-9", "sha256": 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Immunohistochemistry (IHC) was carried out to validate our findin", "genes were conducted. Immunohistochemistry (IHC) was carried out to validate our findings. R", "L1 and SPARCL1 expression, respectively. The IHC results suggested that CHRDL1 and SPARCL1 we"], "order_basis": "paper_text_order:75", "id": "assay:1"}, {"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["to analyze their prognostic value. 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