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pmid:22348113

Computational analysis of mRNA expression profiles identifies microRNA-29a/c as predictor of colorectal cancer early recurrence.

Tai-Yue Kuo · Edward Hsi · I-Ping Yang · Pei-Chien Tsai · Jaw-Yuan Wang · Suh-Hang Hank Juo

PloS one · 2012 doi:10.1371/journal.pone.0031587

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complete

Experiment

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Data

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Analysis

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title
Computational analysis of mRNA expression profiles identifies microRNA-29a/c as predictor of colorectal cancer early recurrence.
doi
10.1371/journal.pone.0031587
pmid
22348113
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Tai-Yue Kuo
[1]
Edward Hsi
[2]
I-Ping Yang
[3]
Pei-Chien Tsai
[4]
Jaw-Yuan Wang
[5]
Suh-Hang Hank Juo
journal
PloS one
year
2012
abstract
Colorectal cancer (CRC) is one of the leading malignant cancers with a rapid increase in incidence and mortality. The recurrences of CRC after curative resection are sometimes unavoidable and often take place within the first year after surgery. MicroRNAs may serve as biomarkers to predict early recurrence of CRC, but identifying them from over 1,400 known human microRNAs is challenging and costly. An alternative approach is to analyze existing expression data of messenger RNAs (mRNAs) because generally speaking the expression levels of microRNAs and their target mRNAs are inversely correlated. In this study, we extracted six mRNA expression data of CRC in four studies (GSE12032, GSE17538, GSE4526 and GSE17181) from the gene expression omnibus (GEO). We inferred microRNA expression profiles and performed computational analysis to identify microRNAs associated with CRC recurrence using the IMRE method based on the MicroCosm database that includes 568,071 microRNA-target connections between 711 microRNAs and 20,884 gene targets. Two microRNAs, miR-29a and miR-29c, were disclosed and further meta-analysis of the six mRNA expression datasets showed that these two microRNAs were highly significant based on the Fisher p-value combination (p = 9.14 × 10(-9) for miR-29a and p = 1.14 × 10(-6) for miR-29c). Furthermore, these two microRNAs were experimentally tested in 78 human CRC samples to validate their effect on early recurrence. Our empirical results showed that the two microRNAs were significantly down-regulated (p = 0.007 for miR-29a and p = 0.007 for miR-29c) in the early-recurrence patients. This study shows the feasibility of using mRNA profiles to indicate microRNAs. We also shows miR-29a/c could be potential biomarkers for CRC early recurrence.
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The random effect model showed an effect size of 213.36 (95% CI: 147.38–279.34) for miR-29a and an effect size of 176.91 (95% CI: 111.63–242.18) for miR-29c.
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The random effect model showed an effect size of 213.36 (95% CI: 147.38–279.34) for miR-29a and an effect size of 176.91 (95% CI: 111.63–242.18) for miR-29c.
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We downloaded their normalized mRNA expression data and sample information from the GEO.
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Inherent gene signature of stage II and III colorectal cancer leads in individual recurrence
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[2]
30/62
[3]
>45.9
[4]
AceGene Human Oligo Chip 30 K(GPL1291)
[5]
29640
[6]
9297
[7]
2009a
[3] array · 8 items
[0]
GSE12032
[1]
III
[2]
47/59
[3]
>45.9
[4]
AceGene Human Oligo Chip 30 K(GPL1291)
[5]
29640
[6]
9297
[7]
2009a
[4] array · 8 items
[0]
GSE17538
[1]
II
[2]
6/17
[3]
68.6 (median)
[4]
HG-U133Plus 2.0 (GPL570)
[5]
54675
[6]
13594
[7]
2009 [44]
[5] array · 8 items
[0]
GSE17538
[1]
III
[2]
15/16
[3]
60 (median)
[4]
HG-U133Plus 2.0 (GPL570)
[5]
54675
[6]
13594
[7]
2009 [44]
[6] array · 8 items
[0]
GSE17181
[1]
II
[2]
16/24
[3]
73 (mean)
[4]
Agilent-014950 CGH Microarray (GPL8841)
[5]
42426
[6]
10630
[7]
2010 [45]
[7] array · 8 items
[0]
GSE4526
[1]
III
[2]
13/23
[3]
54 (median)
[4]
HG-U133Plus 2.0 (GPL570)
[5]
54675
[6]
13056
[7]
2010 [46]
locator
section[3]/table-wrap[1]#pone-0031587-t001
[4] object · 16 fields
id
asset:table:pmid:22348113:2
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table
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jats-table
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application/vnd.jats.table+json
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sha256:abef6abf9bc4a8bb216680352a5518ea34f927081eba56d8d731d5c497e53c38
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section[10]/table-wrap[1]#pone-0031587-t002
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null
note
Association between microRNAs and CRC recurrence of the stage II and III CRC patients in the different datasets.
structure object · 5 fields
pmcid
PMC3278467
section_index
10
section_title
Identification of miR-29a and miR-29c as candidate microRNAs for CRC recurrence
row_count
6
column_count
4
table object · 8 fields
label
Table 2
caption
Association between microRNAs and CRC recurrence of the stage II and III CRC patients in the different datasets.
rows array · 6 items
[0] array · 4 items
[0]
Stage II
[1]
GSE17181 (n = 40)
[2]
GSE12032 (n = 92)
[3]
GSE17538 (n = 23)
[1] array · 4 items
[0]
MiR
[1]
p value
[2]
p value
[3]
p value
[2] array · 4 items
[0]
hsa-miR-29a
[1]
0.08
[2]
<0.01
[3]
0.02
[3] array · 4 items
[0]
hsa-miR-29c
[1]
0.01
[2]
<0.01
[3]
0.03
[4] array · 4 items
[0]
hsa-miR-100
[1]
0.04
[2]
<0.01
[3]
0.02
[5] array · 4 items
[0]
hsa-miR-627
[1]
0.04
[2]
<0.01
[3]
0.02
locator
section[10]/table-wrap[1]#pone-0031587-t002
[5] object · 16 fields
id
asset:table:pmid:22348113:3
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table
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jats-table
media_type
application/vnd.jats.table+json
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null
sha256
sha256:9d442f00af3553494eb0b8148e9266f7c369667e965cea12b2c3027acc673183
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726
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read_table
reader_status
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section[12]/table-wrap[1]#pone-0031587-t003
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null
note
miR-29a and miR-29c expression levels in our CRC samples of early recurrence and non-early recurrence.
structure object · 5 fields
pmcid
PMC3278467
section_index
12
section_title
miR-29a and miR-29c expression level in CRC samples
row_count
10
column_count
5
table object · 8 fields
label
Table 3
caption
miR-29a and miR-29c expression levels in our CRC samples of early recurrence and non-early recurrence.
rows array · 10 items
[0] array · 5 items
[0]
[1]
Non-early recurrence
[2]
Early- recurrence
[3]
Crude
[4]
Adjusted
[1] array · 5 items
[0]
[1]
n = 27
[2]
n = 41
[3]
[4]
[2] array · 5 items
[0]
[1]
mean ± sd
[2]
mean ± sd
[3]
p value
[4]
p value†
[3] array · 5 items
[0]
Age
[1]
68.0±13.0
[2]
65.2±13.9
[3]
0.409
[4]
[4] array · 5 items
[0]
Female, n (%)
[1]
11 (40.7)
[2]
17 (41.5)
[3]
0.953
[4]
[5] array · 5 items
[0]
stage
[1]
[2]
[3]
[4]
[6] array · 5 items
[0]
2
[1]
19 (54.3)
[2]
18 (41.9)
[3]
0.047
[4]
[7] array · 5 items
[0]
3
[1]
8 (22.9)
[2]
23 (53.5)
[3]
[4]
[8] array · 5 items
[0]
miR-29a‡
[1]
1.57±0.51
[2]
1.25±0.49
[3]
0.019
[4]
0.020
[9] array · 5 items
[0]
miR-29c‡
[1]
0.81±0.49
[2]
0.50±0.44
[3]
0.009
[4]
0.009
locator
section[12]/table-wrap[1]#pone-0031587-t003
gaps array · 4 items
[0]
asset:data:geo:GSE12032 not downloaded
[1]
asset:data:geo:GSE12032 licence not read
[2]
asset:data:geo:GSE17538 not downloaded
[3]
asset:data:geo:GSE17538 licence not read
analysis object · 4 fields
state
partial
methods array · 2 items
[0] object · 10 fields
id
method-1
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meta_analysis
specific
random_effects
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Meta-analysis / evidence synthesis
dsl_operations array · 1 item
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random_effects_pool
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
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study_level_effect_estimates
evidence object · 3 fields
score
1
band
verbatim
quote
The random effect model showed an effect size of 213.36 (95% CI: 147.38–279.34) for miR-29a and an effect size of 176.91 (95% CI: 111.63–242.18) for miR-29c.
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id
method-2
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survival_analysis
specific
kaplan_meier
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Survival analysis
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[0]
survival_km
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
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time_to_event_with_censoring
evidence object · 3 fields
score
0.8
band
high
quote
Kaplan-Meier
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gaps array · 1 item
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method.reader_differs_from_extractor
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
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Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
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survival_analysis
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statistical_regression
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pca
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molecular_docking
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network_analysis
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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 · 1 item
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random_effects_pool
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: random_effects.
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 · 3 items
[0]
GSE12032
[1]
GSE17538
[2]
GSE4526 and GSE17181
resolved_accessions array · 2 items
[0]
GSE12032
[1]
GSE17538
statements array · 1 item
[0]
We downloaded their normalized mRNA expression data and sample information from the GEO.
basis
The paper names GSE12032, GSE17538 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 · 1 item
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random_effects_pool
assets array · 5 items
[0]
source:pmid:22348113
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data:geo:GSE12032
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asset:table:pmid:22348113:1
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asset:table:pmid:22348113:2
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asset:table:pmid:22348113:3
steps array · 1 item
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run_analysis
must_build object · 5 fields
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data:geo:GSE12032
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review object · 5 fields
state
partial
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kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
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minimax
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minimax
read_at
null
independence
same_provider
evidence_check object · 2 fields
method
verbatim
availability
null
calls
0
usage object · 0 fields
stages array · 1 item
[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.independent_reader
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review.machine_critique
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review.human_critique
execution object · 5 fields
state
absent
status
not_run
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null
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execution.not_run
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pmid:22348113
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paper
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pmid:22348113
[1] object · 3 fields
id
source:pmid:22348113
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manuscript
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PMID 22348113 full text
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data:geo:GSE12032
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dataset
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GEO GSE12032
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paper
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pmid:22348113
[1] object · 3 fields
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source:pmid:22348113
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PMID 22348113 full text
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GEO GSE12032
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agent:corpus-assay-engine
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agent:minimax-reader
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agent:corpus-assay-engine
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[0]
rom the computational analysis based on mRNA microarray datasets, indicating that the two microRNAs
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paper_text_order:2574
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The random effect model showed an effect size of 213.36 (95% CI: 147.38–279.34) for miR-29a and an effect size of 176.91 (95% CI: 111.63–242.18) for miR-29c.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:22348113", "kind": "science-record", "revision": 7, "content_hash": "sha256:bd4950d8a53408a8aef196673175ab826cd3001045dfef3469271e655c95363e", "created_at": "2026-11-01T15:40:02Z", "updated_at": "2026-11-01T21:19:39Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Computational analysis of mRNA expression profiles identifies microRNA-29a/c as predictor of colorectal cancer early recurrence.", "doi": "10.1371/journal.pone.0031587", "pmid": "22348113", "authors": ["Tai-Yue Kuo", "Edward Hsi", "I-Ping Yang", "Pei-Chien Tsai", "Jaw-Yuan Wang", "Suh-Hang Hank Juo"], "journal": "PloS one", "year": 2012, "abstract": "Colorectal cancer (CRC) is one of the leading malignant cancers with a rapid increase in incidence and mortality. The recurrences of CRC after curative resection are sometimes unavoidable and often take place within the first year after surgery. MicroRNAs may serve as biomarkers to predict early recurrence of CRC, but identifying them from over 1,400 known human microRNAs is challenging and costly. An alternative approach is to analyze existing expression data of messenger RNAs (mRNAs) because generally speaking the expression levels of microRNAs and their target mRNAs are inversely correlated. In this study, we extracted six mRNA expression data of CRC in four studies (GSE12032, GSE17538, GSE4526 and GSE17181) from the gene expression omnibus (GEO). We inferred microRNA expression profiles and performed computational analysis to identify microRNAs associated with CRC recurrence using the IMRE method based on the MicroCosm database that includes 568,071 microRNA-target connections between 711 microRNAs and 20,884 gene targets. Two microRNAs, miR-29a and miR-29c, were disclosed and further meta-analysis of the six mRNA expression datasets showed that these two microRNAs were highly significant based on the Fisher p-value combination (p = 9.14 × 10(-9) for miR-29a and p = 1.14 × 10(-6) for miR-29c). Furthermore, these two microRNAs were experimentally tested in 78 human CRC samples to validate their effect on early recurrence. Our empirical results showed that the two microRNAs were significantly down-regulated (p = 0.007 for miR-29a and p = 0.007 for miR-29c) in the early-recurrence patients. This study shows the feasibility of using mRNA profiles to indicate microRNAs. We also shows miR-29a/c could be potential biomarkers for CRC early recurrence.", "claims": [{"id": "claim-method", "statement": "The random effect model showed an effect size of 213.36 (95% CI: 147.38–279.34) for miR-29a and an effect size of 176.91 (95% CI: 111.63–242.18) for miR-29c.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:22348113", "locator": "sections[11] \"Meta-analysis for miR-29a and miR-29c\" paragraph 2", "quote": "The random effect model showed an effect size of 213.36 (95% CI: 147.38–279.34) for miR-29a and an effect size of 176.91 (95% CI: 111.63–242.18) for miR-29c."}], "state": "complete"}, {"id": "claim-data-access", "statement": "We downloaded their normalized mRNA expression data and sample information from the GEO.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:22348113", "locator": "sections[3] \"Search strategy for mRNA datasets from GEO\" paragraph 2", "quote": "We downloaded their normalized mRNA expression data and sample information from the GEO."}], "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:22348113"], "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:GSE12032"], "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:GSE12032"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:22348113", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0031587", "sha256": 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"access_route": "GEO accession URL", "access_statement_verbatim": "We downloaded their normalized mRNA expression data and sample information from the GEO.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM304101", "GSM304102", "GSM304103", "GSM304104", "GSM304105", "GSM304106", "GSM304107", "GSM304108", "GSM304109", "GSM304110", "GSM304111", "GSM304112", "GSM304113", "GSM304114", "GSM304115", "GSM304116", "GSM304117", "GSM304118", "GSM304119", "GSM304120", "GSM304121", "GSM304122", "GSM304123", "GSM304124", "GSM304125", "GSM304126", "GSM304127", "GSM304128", "GSM304129", "GSM304130", "GSM304131", "GSM304132", "GSM304133", "GSM304134", "GSM304135", "GSM304136", "GSM304137", "GSM304138", "GSM304139", "GSM304140", "GSM304141", "GSM304142", "GSM304143", "GSM304144", "GSM304145", "GSM304146", "GSM304147", "GSM304148", "GSM304149", "GSM304150", "GSM304151", "GSM304152", "GSM304153", "GSM304154", "GSM304155", "GSM304156", "GSM304157", "GSM304158", 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