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pmid:30310500

A miRNA Combination as Promising Biomarker for Hepatocellular Carcinoma Diagnosis: A Study Based on Bioinformatics Analysis.

Jia Ji · Hao Chen · Xiao-Ping Liu · Yu-Hui Wang · Chang-Liang Luo · Wu-Wen Zhang · Wen Xie · Fu-Bing Wang

Journal of Cancer · 2018 doi:10.7150/jca.26101

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title
A miRNA Combination as Promising Biomarker for Hepatocellular Carcinoma Diagnosis: A Study Based on Bioinformatics Analysis.
doi
10.7150/jca.26101
pmid
30310500
authors array · 8 items
[0]
Jia Ji
[1]
Hao Chen
[2]
Xiao-Ping Liu
[3]
Yu-Hui Wang
[4]
Chang-Liang Luo
[5]
Wu-Wen Zhang
[6]
Wen Xie
[7]
Fu-Bing Wang
journal
Journal of Cancer
year
2018
abstract
Background: miRNAs dysregulate in hepatocellular carcinoma (HCC), showing promise for diagnostic biomarkers which may be found through exploration of differentially expressed miRNAs when comparing HCC and normal liver tissues. Materials and Methods: In the present research, candidate miRNAs were selected and verified using screening dataset GSE12717 and training dataset GSE10694, respectively. A miRNA combination was constructed using stepwise logistic regression analysis and validated using two datasets GSE74618 and TCGA. Target genes of miRNAs in the combination were obtained using a miRNA target gene prediction database. Functional analysis was conducted using an online tool DAVID. We also analyzed the mRNA-Seq data of project LIHC from TCGA to identify the hub target genes of the miRNAs. Results: A miRNA combination, which is composed of hsa-miR-221 and hsa-miR-29c was defined in this study. The miRNA combination is more effective in discriminating HCC patients from normal individuals than individual miRNAs. Additionally, the combined miRNAs showed a lower misdiagnosis rate than AFP in HCC diagnosis. In terms of the functional analysis, a total of 27 target genes of hsa-miR-221 and 96 target genes of hsa-miR-29c were obtained. Among which, INSIG1 was the common target of the two miRNAs. It was also found that both previously mentioned miRNAs played important roles in the regulation of transcription, cell proliferation, and involvement in cancer-related pathways. Lastly, 2 hub target genes of hsa-miR-221 and 16 hub target genes of hsa-miR-29c were obtained. Conclusion: We established a miRNA combination as a promising tool for HCC diagnosis, and the target genes we predicted provide possible points of penetration for researching these two miRNAs in HCC.
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Spearman's rank correlation was employed to analyze the relationship between miRNAs and miRNA combinations with clinicopathological variables.
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Spearman's rank correlation was employed to analyze the relationship between miRNAs and miRNA combinations with clinicopathological variables.
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An original microarray dataset, GSE12717 was downloaded from NCBI-Gene Expression Omnibus database (NCBI-GEO) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12717), which is based on the platform of GPL7274 CapitalBio human/mouse/rat non-coding RNA microarray. Expression of 347 miRNAs in 5 human HCC tumor samples and 3 healthy liver samples were available, of which 313 human miRNAs were selected for further analysis.
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sections[4] "Dataset collection and miRNA screening" paragraph 2
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An original microarray dataset, GSE12717 was downloaded from NCBI-Gene Expression Omnibus database (NCBI-GEO) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12717), which is based on the platform of GPL7274 CapitalBio human/mouse/rat non-coding RNA microarray. Expression of 347 miRNAs in 5 human HCC tumor samples and 3 healthy liver samples were available, of which 313 human miRNAs were selected for further analysis.
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GSM1924510
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GSM1924511
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GSM1924512
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GSM1924513
[222]
GSM1924514
[223]
GSM1924515
[224]
GSM1924516
[225]
GSM1924517
[226]
GSM1924518
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GSM1924519
[228]
GSM1924520
[229]
GSM1924521
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GSM1924522
[231]
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[232]
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[233]
GSM1924525
[234]
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[235]
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[236]
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[237]
GSM1924529
[238]
GSM1924530
[239]
GSM1924531
[240]
GSM1924532
[241]
GSM1924533
[242]
GSM1924534
[243]
GSM1924535
[244]
GSM1924536
[245]
GSM1924537
[246]
GSM1924538
[247]
GSM1924539
[248]
GSM1924540
[249]
GSM1924541
sample_count
250
group_sizes
null
group_sizes_basis
null
platform
14613
taxon
Homo sapiens; synthetic construct
title
Re-expression of fetal IGF2 as a target for hepatocellular carcinoma therapy
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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asset:table:pmid:30310500:1
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jats-table
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sha256
sha256:ccece5e4f7e6a061d685de8c9ce7b64d070d0ac7452d9cbf87af1501801ded48
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read_table
reader_status
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section[12]/table-wrap[1]#T1
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note
Candidate miRNAs to establish the diagnostic combination
structure object · 5 fields
pmcid
PMC6171011
section_index
12
section_title
DEmiRNA analysis and screening of candidate miRNAs
row_count
12
column_count
8
table object · 8 fields
label
Table 1
caption
Candidate miRNAs to establish the diagnostic combination
rows array · 12 items
[0] array · 4 items
[0]
miRNA
[1]
Screening dataset
[2]
[3]
Training dataset
[1] array · 7 items
[0]
Log FC
[1]
P value
[2]
type
[3]
[4]
Log FC
[5]
adj.P value
[6]
type
[2] array · 8 items
[0]
Hsa-miR-424
[1]
-3.49307
[2]
0.005137
[3]
Down
[4]
[5]
-1.63196
[6]
3.03E-07
[7]
Down
[3] array · 8 items
[0]
Hsa-miR-520f
[1]
-3.36844
[2]
0.013892
[3]
Down
[4]
[5]
-1.19342
[6]
8.42E-10
[7]
Down
[4] array · 8 items
[0]
Hsa-miR-29c
[1]
-2.27737
[2]
0.03304
[3]
Down
[4]
[5]
-1.84006
[6]
2.17E-08
[7]
Down
[5] array · 8 items
[0]
Hsa-miR-101
[1]
-1.82946
[2]
0.041984
[3]
Down
[4]
[5]
-2.10304
[6]
3.77E-09
[7]
Down
[6] array · 8 items
[0]
Hsa-miR-422a
[1]
-2.61368
[2]
0.001059
[3]
Down
[4]
[5]
-1.03471
[6]
1.36E-09
[7]
Down
[7] array · 8 items
[0]
Hsa-miR-106b
[1]
1.929812
[2]
0.007399
[3]
Up
[4]
[5]
1.270324
[6]
0.000267
[7]
Up
[8] array · 8 items
[0]
Hsa-miR-25
[1]
1.949887
[2]
0.001366
[3]
Up
[4]
[5]
1.690017
[6]
2.23E-07
[7]
Up
[9] array · 8 items
[0]
Hsa-miR-93
[1]
2.217326
[2]
0.003224
[3]
Up
[4]
[5]
1.128434
[6]
0.000155
[7]
Up
[10] array · 8 items
[0]
Hsa-miR-222
[1]
2.491835
[2]
0.000312
[3]
Up
[4]
[5]
2.385102
[6]
1.36E-09
[7]
Up
[11] array · 8 items
[0]
Hsa-miR-221
[1]
1.887786
[2]
0.004491
[3]
Up
[4]
[5]
2.665307
[6]
5.11E-11
[7]
Up
locator
section[12]/table-wrap[1]#T1
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asset:table:pmid:30310500:2
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jats-table
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application/vnd.jats.table+json
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sha256:ba633cc9bb3a4bedd6f1991608e24712aedde5c1e77a955945e5d8bd6ed1bd22
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read_table
reader_status
available
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section[14]/table-wrap[1]#T2
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null
note
Diagnostic accuracy of miRNAs and the miRNA combination
structure object · 5 fields
pmcid
PMC6171011
section_index
14
section_title
Validating the miRNA combination using two different datasets
row_count
12
column_count
7
table object · 8 fields
label
Table 2
caption
Diagnostic accuracy of miRNAs and the miRNA combination
rows array · 12 items
[0] array · 7 items
[0]
Group
[1]
miRNA
[2]
AUC
[3]
P Value
[4]
Sensitivity%
[5]
Specificity%
[6]
95% CI
[1] array · 7 items
[0]
Training dataset
[1]
hsa-miR-221
[2]
0.9859
[3]
<0.0001
[4]
97.44
[5]
100
[6]
0.9634-1.000
[2] array · 6 items
[0]
hsa-miR-29c
[1]
0.9641
[2]
<0.0001
[3]
89.74
[4]
100
[5]
0.9274-1.000
[3] array · 6 items
[0]
miRNA combination
[1]
0.9974
[2]
<0.0001
[3]
98.72
[4]
100
[5]
0.9907-1.000
[4] array · 7 items
[0]
[1]
[2]
[3]
[4]
[5]
[6]
[5] array · 7 items
[0]
Validation dataset GSE74618
[1]
hsa-miR-221
[2]
0.8823
[3]
<0.0001
[4]
75.23
[5]
90
[6]
0.8078-0.9569
[6] array · 6 items
[0]
hsa-miR-29c
[1]
0.6805
[2]
0.05376
[3]
61.93
[4]
80
[5]
0.5655-0.7955
[7] array · 6 items
[0]
miRNA combination
[1]
0.9092
[2]
<0.0001
[3]
86.7
[4]
80
[5]
0.8294-0.9890
[8] array · 7 items
[0]
[1]
[2]
[3]
[4]
[5]
[6]
[9] array · 7 items
[0]
Validation dataset TCGA
[1]
hsa-miR-221
[2]
0.8473
[3]
<0.0001
[4]
74.13
[5]
86
[6]
0.8002-0.8944
[10] array · 6 items
[0]
hsa-miR-29c
[1]
0.9020
[2]
<0.0001
[3]
78.93
[4]
90
[5]
0.8698-0.9341
[11] array · 6 items
[0]
miRNA combination
[1]
0.9641
[2]
<0.0001
[3]
86.67
[4]
98
[5]
0.9474-0.9807
locator
section[14]/table-wrap[1]#T2
[6] object · 16 fields
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asset:table:pmid:30310500:3
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jats-table
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Correlation of miRNAs and miRNA combination with clinicopathological variables in HCC of TCGA datasets
structure object · 5 fields
pmcid
PMC6171011
section_index
15
section_title
The correlation of miRNAs and the miRNA combination with HCC clinicopathological variables
row_count
18
column_count
9
table object · 8 fields
label
Table 3
caption
Correlation of miRNAs and miRNA combination with clinicopathological variables in HCC of TCGA datasets
rows array · 18 items
[0] array · 6 items
[0]
[1]
Group
[2]
Case
[3]
hsa-miR-221
[4]
hsa-miR-29c
[5]
miRNA combination
[1] array · 6 items
[0]
r
[1]
p
[2]
r
[3]
p
[4]
r
[5]
p
[2] array · 9 items
[0]
AFP
[1]
≥20
[2]
131
[3]
0.189
[4]
0.001
[5]
-0.345
[6]
0.00
[7]
0.349
[8]
0.00
[3] array · 2 items
[0]
<20
[1]
151
[4] array · 9 items
[0]
Grade
[1]
1-2
[2]
232
[3]
0.176
[4]
0.001
[5]
-0.194
[6]
0.00
[7]
0.238
[8]
0.00
[5] array · 2 items
[0]
3-4
[1]
137
[6] array · 9 items
[0]
TNM stage
[1]
Ⅰ-Ⅱ
[2]
282
[3]
-0.036
[4]
0.504
[5]
-0.096
[6]
0.073
[7]
0.059
[8]
0.275
[7] array · 2 items
[0]
Ⅲ-Ⅳ
[1]
91
[8] array · 9 items
[0]
Tumor stage
[1]
T0-T1
[2]
184
[3]
-0.056
[4]
0.210
[5]
-0.13
[6]
0.02
[7]
0.03
[8]
0.562
[9] array · 2 items
[0]
T2-T4
[1]
188
[10] array · 9 items
[0]
Lymph-node metastasis
[1]
N0
[2]
255
[3]
-0.039
[4]
0.533
[5]
-0.0102
[6]
0.101
[7]
0.256
[8]
0.071
[11] array · 2 items
[0]
N1
[1]
4
[12] array · 9 items
[0]
Distant metastasis
[1]
M0
[2]
270
[3]
-0.012
[4]
0.839
[5]
-0.003
[6]
0.965
[7]
-0.017
[8]
0.785
[13] array · 2 items
[0]
M1
[1]
4
[14] array · 9 items
[0]
Child-pugh
[1]
A
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221
[3]
0.047
[4]
0.471
[5]
0.027
[6]
0.677
[7]
0.001
[8]
0.993
[15] array · 2 items
[0]
B-C
[1]
22
[16] array · 9 items
[0]
Liver fibrosis
[1]
Yes
[2]
140
[3]
0.156
[4]
0.022
[5]
-0.007
[6]
0.915
[7]
0.12
[8]
0.077
[17] array · 2 items
[0]
No
[1]
76
locator
section[15]/table-wrap[1]#T3
gaps array · 6 items
[0]
asset:data:geo:GSE10694 not downloaded
[1]
asset:data:geo:GSE10694 licence not read
[2]
asset:data:geo:GSE12717 not downloaded
[3]
asset:data:geo:GSE12717 licence not read
[4]
asset:data:geo:GSE74618 not downloaded
[5]
asset:data:geo:GSE74618 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
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method-1
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correlation_analysis
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spearman
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Correlation analysis
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[0]
spearman_rho
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parameters object · 0 fields
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[0]
paired_numeric_columns
evidence object · 3 fields
score
1
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verbatim
quote
Spearman's rank correlation was employed to analyze the relationship between miRNAs and miRNA combinations with clinicopathological variables.
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method-2
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differential_expression
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[0]
normalise_counts
[1]
differential_expression_fit
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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
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high
quote
edgeR
[2] object · 10 fields
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method-3
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differential_expression
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limma_voom
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Differential expression analysis
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[0]
normalise_counts
[1]
differential_expression_fit
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fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
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count_matrix_with_condition
evidence object · 3 fields
score
0.8
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quote
limma
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method-4
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regression_modelling
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logistic
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Regression modelling
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glm_logit_fit
missing_operations array · 0 items
parameters object · 0 fields
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[0]
predictors_and_outcome
evidence object · 3 fields
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0.7
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logistic regression
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parameters object · 0 fields
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[0]
reference_standard_and_test
evidence object · 3 fields
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0.8
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high
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[0]
method.reader_differs_from_extractor
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complete
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capability:computational_analysis
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[0]
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machine_learning
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pca
[5]
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[6]
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differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
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complete
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nothing:replicable_now
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[0]
spearman_rho
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basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: spearman.
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capability:computational_analysis
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The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
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tier
R1
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[0]
GSE12717
[1]
GSE10694
[2]
GSE74618
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[0]
GSE12717
[1]
GSE10694
[2]
GSE74618
statements array · 1 item
[0]
An original microarray dataset, GSE12717 was downloaded from NCBI-Gene Expression Omnibus database (NCBI-GEO) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12717), which is based on the platform of GPL7274 CapitalBio human/mouse/rat non-coding RNA microarray. Expression of 347 miRNAs in 5 human HCC tumor samples and 3 healthy liver samples were available, of which 313 human miRNAs were selected for further analysis.
basis
The paper names GSE12717, GSE10694, GSE74618 in NCBI-Gene Expression Omnibus database (NCBI-GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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spearman_rho
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minimax
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minimax
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2026-10-31T18:12:42Z
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pmid:30310500
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GEO GSE10694
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pmid:30310500
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PMID 30310500 full text
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GEO GSE10694
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[2]
asset:data:geo:GSE12717 licence not read
[3]
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[4]
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[5]
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[6]
execution.not_run
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99e1195c7d6f
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99e1195c7d6f
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[0]
nificantly differentially expressed genes of microarray data were analyzed using R package “limma”,
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f2132e96ae6c7a4e
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spearman_rho
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supported
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Spearman's rank correlation was employed to analyze the relationship between miRNAs and miRNA combinations with clinicopathological variables.
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assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30310500", "kind": "science-record", "revision": 8, "content_hash": "sha256:64e069b41f5398abb2c90a64a9b7cd9de27fa9083bcfb72cda1be2d96f8a8305", "created_at": "2026-11-01T15:40:38Z", "updated_at": "2026-11-01T22:00:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A miRNA Combination as Promising Biomarker for Hepatocellular Carcinoma Diagnosis: A Study Based on Bioinformatics Analysis.", "doi": "10.7150/jca.26101", "pmid": "30310500", "authors": ["Jia Ji", "Hao Chen", "Xiao-Ping Liu", "Yu-Hui Wang", "Chang-Liang Luo", "Wu-Wen Zhang", "Wen Xie", "Fu-Bing Wang"], "journal": "Journal of Cancer", "year": 2018, "abstract": "Background: miRNAs dysregulate in hepatocellular carcinoma (HCC), showing promise for diagnostic biomarkers which may be found through exploration of differentially expressed miRNAs when comparing HCC and normal liver tissues. Materials and Methods: In the present research, candidate miRNAs were selected and verified using screening dataset GSE12717 and training dataset GSE10694, respectively. A miRNA combination was constructed using stepwise logistic regression analysis and validated using two datasets GSE74618 and TCGA. Target genes of miRNAs in the combination were obtained using a miRNA target gene prediction database. Functional analysis was conducted using an online tool DAVID. We also analyzed the mRNA-Seq data of project LIHC from TCGA to identify the hub target genes of the miRNAs. Results: A miRNA combination, which is composed of hsa-miR-221 and hsa-miR-29c was defined in this study. The miRNA combination is more effective in discriminating HCC patients from normal individuals than individual miRNAs. Additionally, the combined miRNAs showed a lower misdiagnosis rate than AFP in HCC diagnosis. In terms of the functional analysis, a total of 27 target genes of hsa-miR-221 and 96 target genes of hsa-miR-29c were obtained. Among which, INSIG1 was the common target of the two miRNAs. It was also found that both previously mentioned miRNAs played important roles in the regulation of transcription, cell proliferation, and involvement in cancer-related pathways. Lastly, 2 hub target genes of hsa-miR-221 and 16 hub target genes of hsa-miR-29c were obtained. Conclusion: We established a miRNA combination as a promising tool for HCC diagnosis, and the target genes we predicted provide possible points of penetration for researching these two miRNAs in HCC.", "claims": [{"id": "claim-method", "statement": "Spearman's rank correlation was employed to analyze the relationship between miRNAs and miRNA combinations with clinicopathological variables.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30310500", "locator": "sections[7] \"Analysis of the correlation of miRNAs and miRNA combination with clinicopathological variables\" paragraph 2", "quote": "Spearman's rank correlation was employed to analyze the relationship between miRNAs and miRNA combinations with clinicopathological variables."}], "state": "complete"}, {"id": "claim-data-access", "statement": "An original microarray dataset, GSE12717 was downloaded from NCBI-Gene Expression Omnibus database (NCBI-GEO) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12717), which is based on the platform of GPL7274 CapitalBio human/mouse/rat non-coding RNA microarray. Expression of 347 miRNAs in 5 human HCC tumor samples and 3 healthy liver samples were available, of which 313 human miRNAs were selected for further analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30310500", "locator": "sections[4] \"Dataset collection and miRNA screening\" paragraph 2", "quote": "An original microarray dataset, GSE12717 was downloaded from NCBI-Gene Expression Omnibus database (NCBI-GEO) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12717), which is based on the platform of GPL7274 CapitalBio human/mouse/rat non-coding RNA microarray. Expression of 347 miRNAs in 5 human HCC tumor samples and 3 healthy liver samples were available, of which 313 human miRNAs were selected for further analysis."}], "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:30310500"], "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:GSE10694"], "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:GSE10694"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30310500", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7150/jca.26101", "sha256": "sha256:fedd6a83faca908d15711230d96b2ef463ba27735b5b39c42c77dc000b2ce943", "bytes": 50992, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7150/jca.26101", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6171011", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE10694", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10694", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE10694", "version": null, "note": "An original microarray dataset, GSE12717 was downloaded from NCBI-Gene Expression Omnibus database (NCBI-GEO) (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12717), which is based on the platform of GPL7274 CapitalBio human/mouse/rat non-coding RNA microarray. 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