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pmid:31059106

Signature microRNAs and long noncoding RNAs in laryngeal cancer recurrence identified using a competing endogenous RNA network.

Zhengyi Tang · Ganguan Wei · Longcheng Zhang · Zhiwen Xu

Molecular medicine reports · 2019 doi:10.3892/mmr.2019.10143

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title
Signature microRNAs and long noncoding RNAs in laryngeal cancer recurrence identified using a competing endogenous RNA network.
doi
10.3892/mmr.2019.10143
pmid
31059106
authors array · 4 items
[0]
Zhengyi Tang
[1]
Ganguan Wei
[2]
Longcheng Zhang
[3]
Zhiwen Xu
journal
Molecular medicine reports
year
2019
abstract
The aim of the present study was to identify novel microRNA (miRNA) or long noncoding RNA (lncRNA) signatures of laryngeal cancer recurrence and to investigate the regulatory mechanisms associated with this malignancy. Datasets of recurrent and nonrecurrent laryngeal cancer samples were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database (GSE27020 and GSE25727) to examine differentially expressed miRNAs (DE‑miRs), lncRNAs (DE‑lncRs) and mRNAs (DEGs). miRNA‑mRNA and lncRNA‑miRNA networks were constructed by investigating the associations among these RNAs in various databases. Subsequently, the interactions identified were combined into a competing endogenous RNA (ceRNA) regulatory network. Feature genes in the miRNA‑mRNA network were identified via topological analysis and a recursive feature elimination algorithm. A support vector machine (SVM) classifier was established using the betweenness centrality values in the miRNA‑mRNA network, consisting of 32 optimal feature‑coding genes. The classification effect was tested using two validation datasets. Furthermore, coding genes in the ceRNA network were examined via pathway enrichment analyses. In total, 21 DE‑lncRs, 507 DEGs and 55 DE‑miRs were selected. The SVM classifier exhibited an accuracy of 94.05% (79/84) for sample classification prediction in the TCGA dataset, and 92.66 and 91.07% in the two validation datasets. The ceRNA regulatory network comprised 203 nodes, corresponding to mRNAs, miRNAs and lncRNAs, and 346 lines, corresponding to the interactions among RNAs. In particular, the interactions with the highest scores were HLA complex group 4 (HCG4)‑miR‑33b, HOX transcript antisense RNA (HOTAIR)‑miR‑1‑MAGE family member A2 (MAGEA2), EMX2 opposite strand/antisense RNA (EMX2OS)‑miR‑124‑calcitonin related polypeptide α (CALCA) and EMX2OS‑miR‑124‑γ‑aminobutyric acid type A receptor γ2 subunit (GABRG2). Gene enrichment analysis of the genes in the ceRNA network identified that 11 pathway terms and 16 molecular function terms were significantly enriched. The SVM classifier based on 32 feature coding genes exhibited high accuracy in the classification of laryngeal cancer samples. miR‑1, miR‑33b, miR‑124, HOTAIR, HCG4 and EMX2OS may be novel biomarkers of recurrent laryngeal cancer, and HCG4‑miR‑33b, HOTAIR‑miR‑1‑MAGEA2 and EMX2OS‑miR‑124‑CALCA/GABRG2 may be associated with the molecular mechanisms regulating recurrent laryngeal cancer.
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Identification and validation of gene expression models that predict clinical outcome in patients with early stage laryngeal cancer
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Identification and validation of a multigene predictor of recurrence in primary laryngeal cancer.
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Significantly enriched pathways in the competing endogenous RNA regulatory network.
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Table III.
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Significantly enriched pathways in the competing endogenous RNA regulatory network.
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KEGG pathway name
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Differentially expressed genes
[1] array · 5 items
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hsa04530
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Significantly enriched molecular functions in the competing endogenous RNA regulatory network.
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Significantly enriched molecular functions in the competing endogenous RNA regulatory network.
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[0] array · 5 items
[0]
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[1]
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[3]
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[4]
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[3]
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18
[3]
1.32×10−4
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[1]
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11
[3]
1.44×10−4
[4]
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GO:0030182
[1]
Neuron differentiation
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13
[3]
2.09×10−4
[4]
NCAM2, SLITRK4, SOX1, OPCML, FOXA2, PKHD1, EMX2, MDGA2, PTPRR, POU4F1, OLFM3, NEFL, CTNNA2
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[0]
GO:0019226
[1]
Transmission of nerve impulse
[2]
11
[3]
5.20×10−4
[4]
GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2
[10] array · 5 items
[0]
GO:0055082
[1]
Cellular chemical homeostasis
[2]
10
[3]
3.60×10−3
[4]
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[11] array · 5 items
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GO:0019725
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10
[3]
1.29×10−2
[4]
CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1
[12] array · 5 items
[0]
GO:0048878
[1]
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10
[3]
2.24×10−2
[4]
CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1
[13] array · 5 items
[0]
GO:0007155
[1]
Cell adhesion
[2]
12
[3]
2.54×10−2
[4]
IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, FAT3, PKHD1, CLDN6, CLDN22, CLDN10, CTNNA2
[14] array · 5 items
[0]
GO:0022610
[1]
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12
[3]
2.56×10−2
[4]
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GO:0050877
[1]
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[2]
17
[3]
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[4]
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GO:0042592
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[3]
3.94×10−2
[4]
CALCA, CALCB, XIRP1, GRIK2, PKHD1, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1, EPO
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Basic information of 32 optimal feature-coding genes, among the genes significantly differentially expressed between recurrent and nonrecurrent cancer samples.
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PMC6522811
section_index
17
section_title
SVM classifier
row_count
33
column_count
5
table object · 8 fields
label
Table I.
caption
Basic information of 32 optimal feature-coding genes, among the genes significantly differentially expressed between recurrent and nonrecurrent cancer samples.
rows array · 33 items
[0] array · 5 items
[0]
Gene symbol
[1]
Betweenness centrality
[2]
Number of interactions
[3]
P-value
[4]
Log2 fold-change
[1] array · 5 items
[0]
SHISA6
[1]
0.240
[2]
4
[3]
0.028
[4]
0.544
[2] array · 5 items
[0]
MAGEA2
[1]
0.215
[2]
5
[3]
0.047
[4]
−0.394
[3] array · 5 items
[0]
TRDN
[1]
0.156
[2]
6
[3]
0.002
[4]
0.601
[4] array · 5 items
[0]
RGS7
[1]
0.149
[2]
4
[3]
0.001
[4]
1.331
[5] array · 5 items
[0]
CPNE4
[1]
0.142
[2]
4
[3]
0.020
[4]
0.657
[6] array · 5 items
[0]
CALCA
[1]
0.111
[2]
3
[3]
0.004
[4]
1.214
[7] array · 5 items
[0]
GABRG2
[1]
0.101
[2]
2
[3]
0.035
[4]
0.599
[8] array · 5 items
[0]
TECRL
[1]
0.083
[2]
3
[3]
0.043
[4]
0.846
[9] array · 5 items
[0]
MYLK2
[1]
0.073
[2]
3
[3]
0.005
[4]
0.543
[10] array · 5 items
[0]
MYO3A
[1]
0.058
[2]
3
[3]
0.048
[4]
0.365
[11] array · 5 items
[0]
ASB10
[1]
0.057
[2]
3
[3]
0.001
[4]
1.261
[12] array · 5 items
[0]
WT1
[1]
0.039
[2]
4
[3]
0.015
[4]
0.712
[13] array · 5 items
[0]
CALCB
[1]
0.038
[2]
2
[3]
0.006
[4]
0.986
[14] array · 5 items
[0]
OPCML
[1]
0.038
[2]
2
[3]
0.011
[4]
0.693
[15] array · 5 items
[0]
KY
[1]
0.038
[2]
2
[3]
0.011
[4]
0.502
[16] array · 5 items
[0]
CYP3A43
[1]
0.038
[2]
2
[3]
0.027
[4]
−2.312
[17] array · 5 items
[0]
EPHA6
[1]
0.038
[2]
2
[3]
0.001
[4]
1.216
[18] array · 5 items
[0]
SLC6A20
[1]
0.038
[2]
2
[3]
0.001
[4]
0.583
[19] array · 5 items
[0]
NCAM2
[1]
0.036
[2]
2
[3]
0.026
[4]
0.451
[20] array · 5 items
[0]
FLRT3
[1]
0.033
[2]
2
[3]
0.022
[4]
0.312
[21] array · 5 items
[0]
TMC5
[1]
0.033
[2]
2
[3]
0.034
[4]
−0.334
[22] array · 5 items
[0]
AADACL3
[1]
0.033
[2]
2
[3]
0.011
[4]
0.983
[23] array · 5 items
[0]
ANKRD1
[1]
0.026
[2]
6
[3]
0.005
[4]
0.520
[24] array · 5 items
[0]
CLDN22
[1]
0.020
[2]
2
[3]
0.005
[4]
−1.662
[25] array · 5 items
[0]
FGF5
[1]
0.018
[2]
2
[3]
0.015
[4]
0.593
[26] array · 5 items
[0]
SCN5A
[1]
0.016
[2]
2
[3]
0.009
[4]
0.475
[27] array · 5 items
[0]
PTPRR
[1]
0.016
[2]
2
[3]
0.005
[4]
0.561
[28] array · 5 items
[0]
LDHC
[1]
0.015
[2]
2
[3]
0.000
[4]
−1.366
[29] array · 5 items
[0]
OLFM3
[1]
0.012
[2]
2
[3]
0.036
[4]
1.283
[30] array · 5 items
[0]
HRASLS5
[1]
0.012
[2]
2
[3]
0.042
[4]
−0.560
[31] array · 5 items
[0]
SPINK6
[1]
0.010
[2]
2
[3]
0.011
[4]
−0.533
[32] array · 5 items
[0]
SPESP1
[1]
0.008
[2]
2
[3]
0.004
[4]
0.499
locator
section[17]/table-wrap[1]#tI-mmr-19-06-4806
[6] object · 16 fields
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asset:table:pmid:31059106:4
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table
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jats-table
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application/vnd.jats.table+json
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null
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sha256:5734f893d821a46857a2bee7799ec63780011e9642e7dc1341759657ced2020e
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reader_status
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section[17]/table-wrap[2]#tII-mmr-19-06-4806
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null
note
Classifying parameters of the support vector machine classifier for the three datasets analyzed.
structure object · 5 fields
pmcid
PMC6522811
section_index
17
section_title
SVM classifier
row_count
4
column_count
8
table object · 8 fields
label
Table II.
caption
Classifying parameters of the support vector machine classifier for the three datasets analyzed.
rows array · 4 items
[0] array · 8 items
[0]
Dataset
[1]
Number of samples
[2]
Accuracy
[3]
Sensitivity
[4]
Specificity
[5]
Positive predictive value
[6]
Negative predictive value
[7]
Area under receiver operating characteristic curve
[1] array · 8 items
[0]
TCGA
[1]
84
[2]
0.9410
[3]
0.947
[4]
0.938
[5]
0.818
[6]
0.984
[7]
0.986
[2] array · 8 items
[0]
GSE27020
[1]
109
[2]
0.9266
[3]
0.882
[4]
0.947
[5]
0.882
[6]
0.947
[7]
0.946
[3] array · 8 items
[0]
GSE25727
[1]
56
[2]
0.9107
[3]
0.941
[4]
0.897
[5]
0.8
[6]
0.972
[7]
0.921
locator
section[17]/table-wrap[2]#tII-mmr-19-06-4806
[7] object · 16 fields
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asset:table:pmid:31059106:5
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table
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jats-table
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application/vnd.jats.table+json
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null
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sha256:a745b59a26bbb2d9807a265a8ce64efd9ff197b00c16e681b799431bab7d5ca1
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section[18]/table-wrap[1]#tIII-mmr-19-06-4806
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null
note
Significantly enriched pathways in the competing endogenous RNA regulatory network.
structure object · 5 fields
pmcid
PMC6522811
section_index
18
section_title
Molecular function and pathway enrichment analysis
row_count
12
column_count
5
table object · 8 fields
label
Table III.
caption
Significantly enriched pathways in the competing endogenous RNA regulatory network.
rows array · 12 items
[0] array · 5 items
[0]
KEGG pathway ID
[1]
KEGG pathway name
[2]
Gene count
[3]
P-value
[4]
Differentially expressed genes
[1] array · 5 items
[0]
hsa04530
[1]
Tight junction
[2]
5
[3]
0.001
[4]
MYH1, CLDN6, MYH4, CTNNA2, CLDN10
[2] array · 5 items
[0]
hsa04970
[1]
Salivary secretion
[2]
4
[3]
0.001
[4]
HTN3, ATP1B4, ATP1A2, STATH
[3] array · 5 items
[0]
hsa04080
[1]
Neuroactive ligand-receptor interaction
[2]
6
[3]
0.004
[4]
GABRA2, GABRG2, PTH2R, OPRK1, CHRNA1, GRIK2
[4] array · 5 items
[0]
hsa04918
[1]
Thyroid hormone synthesis
[2]
3
[3]
0.007
[4]
6528, ATP1B4, ATP1A2
[5] array · 5 items
[0]
hsa04964
[1]
Proximal tubule bicarbonate reclamation
[2]
2
[3]
0.008
[4]
ATP1B4, ATP1A2
[6] array · 5 items
[0]
hsa04960
[1]
Aldosterone-regulated sodium reabsorption
[2]
2
[3]
0.020
[4]
ATP1B4, ATP1A2
[7] array · 5 items
[0]
hsa05033
[1]
Nicotine addiction
[2]
2
[3]
0.020
[4]
GABRA2, GABRG2
[8] array · 5 items
[0]
hsa04973
[1]
Carbohydrate digestion and absorption
[2]
2
[3]
0.025
[4]
ATP1B4, ATP1A2
[9] array · 5 items
[0]
hsa04670
[1]
Leukocyte transendothelial migration
[2]
3
[3]
0.026
[4]
CLDN6, CTNNA2, CLDN10
[10] array · 5 items
[0]
hsa04978
[1]
Mineral absorption
[2]
2
[3]
0.032
[4]
ATP1B4, ATP1A2
[11] array · 5 items
[0]
hsa04514
[1]
Cell adhesion molecules (CAMs)
[2]
3
[3]
0.041
[4]
CLDN6, NCAM2, CLDN10
locator
section[18]/table-wrap[1]#tIII-mmr-19-06-4806
[8] object · 16 fields
id
asset:table:pmid:31059106:6
role
table
format
jats-table
media_type
application/vnd.jats.table+json
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null
sha256
sha256:2df3e319f66e1ea49df05d1e0275a1306a3c496d0fda80412c2746cd42e2d9b9
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2665
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read_table
reader_status
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section[18]/table-wrap[2]#tIV-mmr-19-06-4806
version
null
note
Significantly enriched molecular functions in the competing endogenous RNA regulatory network.
structure object · 5 fields
pmcid
PMC6522811
section_index
18
section_title
Molecular function and pathway enrichment analysis
row_count
17
column_count
5
table object · 8 fields
label
Table IV.
caption
Significantly enriched molecular functions in the competing endogenous RNA regulatory network.
rows array · 17 items
[0] array · 5 items
[0]
GO term ID
[1]
GO term name
[2]
Gene count
[3]
P-value
[4]
Genes
[1] array · 5 items
[0]
GO:0006936
[1]
Muscle contraction
[2]
11
[3]
4.17×10−7
[4]
TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2
[2] array · 5 items
[0]
GO:0003012
[1]
Muscle system process
[2]
11
[3]
9.88×10−7
[4]
TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2
[3] array · 5 items
[0]
GO:0008015
[1]
Blood circulation
[2]
10
[3]
1.89×10−5
[4]
CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO
[4] array · 5 items
[0]
GO:0003013
[1]
Circulatory system process
[2]
10
[3]
1.89×10−5
[4]
CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO
[5] array · 5 items
[0]
GO:0007267
[1]
Cell-cell signaling
[2]
16
[3]
9.03×10−5
[4]
FGF5, GABRG2, GABRA2, GRIK2, OPRK1, MYLK2, ATP1A2, CXCL6, IL22, CTNNA2, CALCA, PNOC, SLC1A6, CARTPT, SLC30A8, CHRNA1
[6] array · 5 items
[0]
GO:0006811
[1]
Ion transport
[2]
18
[3]
1.32×10−4
[4]
GABRG2, SLC5A5, GABRA2, GRIK2, ATP1B4, KCNA6, ATP1A2, TCN1, BEST3, SLC1A6, SLC5A8, LTF, ANO5, ANO4, CHRNA1, SLC30A8, SCN5A, ADD2
[7] array · 5 items
[0]
GO:0007268
[1]
Synaptic transmission
[2]
11
[3]
1.44×10−4
[4]
GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2
[8] array · 5 items
[0]
GO:0030182
[1]
Neuron differentiation
[2]
13
[3]
2.09×10−4
[4]
NCAM2, SLITRK4, SOX1, OPCML, FOXA2, PKHD1, EMX2, MDGA2, PTPRR, POU4F1, OLFM3, NEFL, CTNNA2
[9] array · 5 items
[0]
GO:0019226
[1]
Transmission of nerve impulse
[2]
11
[3]
5.20×10−4
[4]
GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2
[10] array · 5 items
[0]
GO:0055082
[1]
Cellular chemical homeostasis
[2]
10
[3]
3.60×10−3
[4]
CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1
[11] array · 5 items
[0]
GO:0019725
[1]
Cellular homeostasis
[2]
10
[3]
1.29×10−2
[4]
CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1
[12] array · 5 items
[0]
GO:0048878
[1]
Chemical homeostasis
[2]
10
[3]
2.24×10−2
[4]
CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1
[13] array · 5 items
[0]
GO:0007155
[1]
Cell adhesion
[2]
12
[3]
2.54×10−2
[4]
IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, FAT3, PKHD1, CLDN6, CLDN22, CLDN10, CTNNA2
[14] array · 5 items
[0]
GO:0022610
[1]
Biological adhesion
[2]
12
[3]
2.56×10−2
[4]
IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, FAT3, PKHD1, CLDN6, CLDN22, CLDN10, CTNNA2
[15] array · 5 items
[0]
GO:0050877
[1]
Neurological system process
[2]
17
[3]
3.28×10−2
[4]
GABRG2, GABRA2, MYO3A, GRIK2, OPRK1, MYLK2, ATP1A2, TAS1R1, CTNNA2, CALCA, NCAM2, PNOC, SLC1A6, CARTPT, POU4F1, CHRNA1, NEFL
[16] array · 5 items
[0]
GO:0042592
[1]
Homeostatic process
[2]
12
[3]
3.94×10−2
[4]
CALCA, CALCB, XIRP1, GRIK2, PKHD1, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1, EPO
locator
section[18]/table-wrap[2]#tIV-mmr-19-06-4806
gaps array · 4 items
[0]
asset:data:geo:GSE25727 not downloaded
[1]
asset:data:geo:GSE25727 licence not read
[2]
asset:data:geo:GSE27020 not downloaded
[3]
asset:data:geo:GSE27020 licence not read
analysis object · 4 fields
state
complete
methods array · 5 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
edger
label
Differential expression analysis
dsl_operations array · 3 items
[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
1
band
verbatim
quote
The differentially expressed RNAs, including differentially expressed mRNAs (DEGs), differentially expressed lncRNAs (DE-lncRs) and differentially expressed miRNAs (DE-miRs), between recurrent and nonrecurrent laryngeal cancer samples were analyzed using the EdgeR package version 3.8.5, which adopted an overdispersed poisson model and an empirical Bayesian approach to improve the reliability of the prediction (23).
[1] object · 10 fields
id
method-2
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[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
[2] object · 10 fields
id
method-3
family
machine_learning
specific
support_vector_machine
label
Machine learning
dsl_operations array · 3 items
[0]
train_classifier
[1]
cross_validate
[2]
roc_auc
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
medium
quote
support vector machine
[3] object · 10 fields
id
method-4
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
0.7
band
medium
quote
pathway enrichment
[4] object · 10 fields
id
method-5
family
network_analysis
specific
centrality
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
centrality
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
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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: edger.
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 · 2 items
[0]
GSE27020
[1]
GSE25727
resolved_accessions array · 2 items
[0]
GSE27020
[1]
GSE25727
statements array · 1 item
[0]
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
basis
The paper names GSE27020, GSE25727 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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 8 items
[0]
source:pmid:31059106
[1]
data:geo:GSE25727
[2]
asset:table:pmid:31059106:1
[3]
asset:table:pmid:31059106:2
[4]
asset:table:pmid:31059106:3
[5]
asset:table:pmid:31059106:4
[6]
asset:table:pmid:31059106:5
[7]
asset:table:pmid:31059106:6
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:GSE25727
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
2026-10-31T18:14:37Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
39432
completion_tokens
1657
cached_tokens
520
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
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et was constructed using the RNA sequencing (RNA-seq) data downloaded from the TCGA database. The
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e training dataset was constructed using the RNA sequencing (RNA-seq) data downloaded from the TCGA data
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The differentially expressed RNAs, including differentially expressed mRNAs (DEGs), differentially expressed lncRNAs (DE-lncRs) and differentially expressed miRNAs (DE-miRs), between recurrent and nonrecurrent laryngeal cancer samples were analyzed using the EdgeR package version 3.8.5, which adopted an overdispersed poisson model and an empirical Bayesian approach to improve the reliability of the prediction (23).
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Complete file
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Datasets of recurrent and nonrecurrent laryngeal cancer samples were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database (GSE27020 and GSE25727) to examine differentially expressed miRNAs (DE‑miRs), lncRNAs (DE‑lncRs) and mRNAs (DEGs). miRNA‑mRNA and lncRNA‑miRNA networks were constructed by investigating the associations among these RNAs in various databases. Subsequently, the interactions identified were combined into a competing endogenous RNA (ceRNA) regulatory network. Feature genes in the miRNA‑mRNA network were identified via topological analysis and a recursive feature elimination algorithm. A support vector machine (SVM) classifier was established using the betweenness centrality values in the miRNA‑mRNA network, consisting of 32 optimal feature‑coding genes. The classification effect was tested using two validation datasets. Furthermore, coding genes in the ceRNA network were examined via pathway enrichment analyses. In total, 21 DE‑lncRs, 507 DEGs and 55 DE‑miRs were selected. The SVM classifier exhibited an accuracy of 94.05% (79/84) for sample classification prediction in the TCGA dataset, and 92.66 and 91.07% in the two validation datasets. The ceRNA regulatory network comprised 203 nodes, corresponding to mRNAs, miRNAs and lncRNAs, and 346 lines, corresponding to the interactions among RNAs. In particular, the interactions with the highest scores were HLA complex group 4 (HCG4)‑miR‑33b, HOX transcript antisense RNA (HOTAIR)‑miR‑1‑MAGE family member A2 (MAGEA2), EMX2 opposite strand/antisense RNA (EMX2OS)‑miR‑124‑calcitonin related polypeptide α (CALCA) and EMX2OS‑miR‑124‑γ‑aminobutyric acid type A receptor γ2 subunit (GABRG2). Gene enrichment analysis of the genes in the ceRNA network identified that 11 pathway terms and 16 molecular function terms were significantly enriched. The SVM classifier based on 32 feature coding genes exhibited high accuracy in the classification of laryngeal cancer samples. miR‑1, miR‑33b, miR‑124, HOTAIR, HCG4 and EMX2OS may be novel biomarkers of recurrent laryngeal cancer, and HCG4‑miR‑33b, HOTAIR‑miR‑1‑MAGEA2 and EMX2OS‑miR‑124‑CALCA/GABRG2 may be associated with the molecular mechanisms regulating recurrent laryngeal cancer.", "claims": [{"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31059106", "locator": "sections[23] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "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:31059106"], "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:GSE25727"], "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:GSE25727"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31059106", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3892/mmr.2019.10143", "sha256": 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"Genes"], ["GO:0006936", "Muscle contraction", "11", "4.17×10−7", "TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2"], ["GO:0003012", "Muscle system process", "11", "9.88×10−7", "TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2"], ["GO:0008015", "Blood circulation", "10", "1.89×10−5", "CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO"], ["GO:0003013", "Circulatory system process", "10", "1.89×10−5", "CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO"], ["GO:0007267", "Cell-cell signaling", "16", "9.03×10−5", "FGF5, GABRG2, GABRA2, GRIK2, OPRK1, MYLK2, ATP1A2, CXCL6, IL22, CTNNA2, CALCA, PNOC, SLC1A6, CARTPT, SLC30A8, CHRNA1"], ["GO:0006811", "Ion transport", "18", "1.32×10−4", "GABRG2, SLC5A5, GABRA2, GRIK2, ATP1B4, KCNA6, ATP1A2, TCN1, BEST3, SLC1A6, SLC5A8, LTF, ANO5, ANO4, CHRNA1, SLC30A8, SCN5A, ADD2"], ["GO:0007268", "Synaptic transmission", "11", "1.44×10−4", "GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2"], ["GO:0030182", "Neuron differentiation", "13", "2.09×10−4", "NCAM2, SLITRK4, SOX1, OPCML, FOXA2, PKHD1, EMX2, MDGA2, PTPRR, POU4F1, OLFM3, NEFL, CTNNA2"], ["GO:0019226", "Transmission of nerve impulse", "11", "5.20×10−4", "GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2"], ["GO:0055082", "Cellular chemical homeostasis", "10", "3.60×10−3", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0019725", "Cellular homeostasis", "10", "1.29×10−2", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0048878", "Chemical homeostasis", "10", "2.24×10−2", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0007155", "Cell adhesion", "12", "2.54×10−2", "IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, FAT3, PKHD1, CLDN6, CLDN22, CLDN10, CTNNA2"], ["GO:0022610", "Biological adhesion", "12", "2.56×10−2", "IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, 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among the genes significantly differentially expressed between recurrent and nonrecurrent cancer samples.", "structure": {"pmcid": "PMC6522811", "section_index": 17, "section_title": "SVM classifier", "row_count": 33, "column_count": 5}, "table": {"label": "Table I.", "caption": "Basic information of 32 optimal feature-coding genes, among the genes significantly differentially expressed between recurrent and nonrecurrent cancer samples.", "rows": [["Gene symbol", "Betweenness centrality", "Number of interactions", "P-value", "Log2 fold-change"], ["SHISA6", "0.240", "4", "0.028", "0.544"], ["MAGEA2", "0.215", "5", "0.047", "−0.394"], ["TRDN", "0.156", "6", "0.002", "0.601"], ["RGS7", "0.149", "4", "0.001", "1.331"], ["CPNE4", "0.142", "4", "0.020", "0.657"], ["CALCA", "0.111", "3", "0.004", "1.214"], ["GABRG2", "0.101", "2", "0.035", "0.599"], ["TECRL", "0.083", "3", "0.043", "0.846"], ["MYLK2", "0.073", "3", "0.005", "0.543"], ["MYO3A", "0.058", "3", "0.048", "0.365"], ["ASB10", 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predictive value", "Area under receiver operating characteristic curve"], ["TCGA", "84", "0.9410", "0.947", "0.938", "0.818", "0.984", "0.986"], ["GSE27020", "109", "0.9266", "0.882", "0.947", "0.882", "0.947", "0.946"], ["GSE25727", "56", "0.9107", "0.941", "0.897", "0.8", "0.972", "0.921"]], "row_count": 4, "column_count": 8, "numeric_cells": 23, "header_rows": 1, "locator": "section[17]/table-wrap[2]#tII-mmr-19-06-4806"}}, {"id": "asset:table:pmid:31059106:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:a745b59a26bbb2d9807a265a8ce64efd9ff197b00c16e681b799431bab7d5ca1", "bytes": 1238, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[1]#tIII-mmr-19-06-4806", "version": null, "note": "Significantly enriched pathways in the competing endogenous RNA regulatory network.", "structure": {"pmcid": "PMC6522811", "section_index": 18, "section_title": "Molecular function and pathway enrichment analysis", "row_count": 12, "column_count": 5}, "table": {"label": "Table III.", "caption": "Significantly enriched pathways in the competing endogenous RNA regulatory network.", "rows": [["KEGG pathway ID", "KEGG pathway name", "Gene count", "P-value", "Differentially expressed genes"], ["hsa04530", "Tight junction", "5", "0.001", "MYH1, CLDN6, MYH4, CTNNA2, CLDN10"], ["hsa04970", "Salivary secretion", "4", "0.001", "HTN3, ATP1B4, ATP1A2, STATH"], ["hsa04080", "Neuroactive ligand-receptor interaction", "6", "0.004", "GABRA2, GABRG2, PTH2R, OPRK1, CHRNA1, GRIK2"], ["hsa04918", "Thyroid hormone synthesis", "3", "0.007", "6528, ATP1B4, ATP1A2"], ["hsa04964", "Proximal tubule bicarbonate reclamation", "2", "0.008", "ATP1B4, ATP1A2"], ["hsa04960", "Aldosterone-regulated sodium reabsorption", "2", "0.020", "ATP1B4, ATP1A2"], ["hsa05033", "Nicotine addiction", "2", "0.020", "GABRA2, GABRG2"], ["hsa04973", "Carbohydrate digestion and absorption", "2", "0.025", "ATP1B4, ATP1A2"], ["hsa04670", "Leukocyte transendothelial migration", "3", "0.026", "CLDN6, CTNNA2, CLDN10"], ["hsa04978", "Mineral absorption", "2", "0.032", "ATP1B4, ATP1A2"], ["hsa04514", "Cell adhesion molecules (CAMs)", "3", "0.041", "CLDN6, NCAM2, CLDN10"]], "row_count": 12, "column_count": 5, "numeric_cells": 37, "header_rows": 1, "locator": "section[18]/table-wrap[1]#tIII-mmr-19-06-4806"}}, {"id": "asset:table:pmid:31059106:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:2df3e319f66e1ea49df05d1e0275a1306a3c496d0fda80412c2746cd42e2d9b9", "bytes": 2665, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[18]/table-wrap[2]#tIV-mmr-19-06-4806", "version": null, "note": "Significantly enriched molecular functions in the competing endogenous RNA regulatory network.", "structure": {"pmcid": "PMC6522811", "section_index": 18, "section_title": "Molecular function and pathway enrichment analysis", "row_count": 17, "column_count": 5}, "table": {"label": "Table IV.", "caption": "Significantly enriched molecular functions in the competing endogenous RNA regulatory network.", "rows": [["GO term ID", "GO term name", "Gene count", "P-value", "Genes"], ["GO:0006936", "Muscle contraction", "11", "4.17×10−7", "TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2"], ["GO:0003012", "Muscle system process", "11", "9.88×10−7", "TRDN, ACTC1, MYH1, MYL1, MYLK2, MYH4, SMPX, TTN, CHRNA1, SCN5A, CASQ2"], ["GO:0008015", "Blood circulation", "10", "1.89×10−5", "CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO"], ["GO:0003013", "Circulatory system process", "10", "1.89×10−5", "CALCA, CALCB, ACTC1, MYL1, MYLK2, CARTPT, ATP1A2, TAC4, SCN5A, EPO"], ["GO:0007267", "Cell-cell signaling", "16", "9.03×10−5", "FGF5, GABRG2, GABRA2, GRIK2, OPRK1, MYLK2, ATP1A2, CXCL6, IL22, CTNNA2, CALCA, PNOC, SLC1A6, CARTPT, SLC30A8, CHRNA1"], ["GO:0006811", "Ion transport", "18", "1.32×10−4", "GABRG2, SLC5A5, GABRA2, GRIK2, ATP1B4, KCNA6, ATP1A2, TCN1, BEST3, SLC1A6, SLC5A8, LTF, ANO5, ANO4, CHRNA1, SLC30A8, SCN5A, ADD2"], ["GO:0007268", "Synaptic transmission", "11", "1.44×10−4", "GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2"], ["GO:0030182", "Neuron differentiation", "13", "2.09×10−4", "NCAM2, SLITRK4, SOX1, OPCML, FOXA2, PKHD1, EMX2, MDGA2, PTPRR, POU4F1, OLFM3, NEFL, CTNNA2"], ["GO:0019226", "Transmission of nerve impulse", "11", "5.20×10−4", "GABRG2, GABRA2, PNOC, GRIK2, OPRK1, SLC1A6, MYLK2, CARTPT, ATP1A2, CHRNA1, CTNNA2"], ["GO:0055082", "Cellular chemical homeostasis", "10", "3.60×10−3", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0019725", "Cellular homeostasis", "10", "1.29×10−2", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0048878", "Chemical homeostasis", "10", "2.24×10−2", "CALCA, CALCB, XIRP1, GRIK2, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1"], ["GO:0007155", "Cell adhesion", "12", "2.54×10−2", "IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, FAT3, PKHD1, CLDN6, CLDN22, CLDN10, CTNNA2"], ["GO:0022610", "Biological adhesion", "12", "2.56×10−2", "IBSP, FLRT3, CALCA, NCAM2, AMBN, OPCML, FAT3, PKHD1, CLDN6, CLDN22, CLDN10, CTNNA2"], ["GO:0050877", "Neurological system process", "17", "3.28×10−2", "GABRG2, GABRA2, MYO3A, GRIK2, OPRK1, MYLK2, ATP1A2, TAS1R1, CTNNA2, CALCA, NCAM2, PNOC, SLC1A6, CARTPT, POU4F1, CHRNA1, NEFL"], ["GO:0042592", "Homeostatic process", "12", "3.94×10−2", "CALCA, CALCB, XIRP1, GRIK2, PKHD1, SLC1A6, LTF, CARTPT, ATP1A2, SLC30A8, CHRNA1, EPO"]], "row_count": 17, "column_count": 5, "numeric_cells": 56, "header_rows": 1, "locator": "section[18]/table-wrap[2]#tIV-mmr-19-06-4806"}}], "gaps": ["asset:data:geo:GSE25727 not downloaded", "asset:data:geo:GSE25727 licence not read", "asset:data:geo:GSE27020 not 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