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pmid:31815134

A Novel Clinical Six-Flavoprotein-Gene Signature Predicts Prognosis in Esophageal Squamous Cell Carcinoma.

Liu Peng · Jin-Cheng Guo · Lin Long · Feng Pan · Jian-Mei Zhao · Li-Yan Xu · En-Min Li

BioMed research international · 2019 doi:10.1155/2019/3869825

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Experiment

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Data

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Analysis

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title
A Novel Clinical Six-Flavoprotein-Gene Signature Predicts Prognosis in Esophageal Squamous Cell Carcinoma.
doi
10.1155/2019/3869825
pmid
31815134
authors array · 7 items
[0]
Liu Peng
[1]
Jin-Cheng Guo
[2]
Lin Long
[3]
Feng Pan
[4]
Jian-Mei Zhao
[5]
Li-Yan Xu
[6]
En-Min Li
journal
BioMed research international
year
2019
abstract
Flavoproteins and their interacting proteins play important roles in mitochondrial electron transport, fatty acid degradation, and redox regulation. However, their clinical significance and function in esophageal squamous cell carcinoma (ESCC) are little known. Here, using survival analysis and machine learning, we mined 179 patient expression profiles with ESCC in GSE53625 from the Gene Expression Omnibus (GEO) database and constructed a signature consisting of two flavoprotein genes (GPD2 and PYROXD2) and four flavoprotein interacting protein genes (CTTN, GGH, SRC, and SYNJ2BP). Kaplan-Meier analysis revealed the signature was significantly associated with the survival of ESCC patients (mean survival time: 26.77 months in the high-risk group vs. 54.97 months in the low-risk group, P < 0.001, n = 179), and time-dependent ROC analysis demonstrated that the six-gene signature had good predictive ability for six-year survival for ESCC (AUC = 0.86, 95% CI: 0.81-0.90). We then validated its prediction performance in an independent set by RT-PCR (mean survival: 15.73 months in the high-risk group vs. 21.1 months in the low-risk group, P=0.032, n = 121). Furthermore, RNAi-mediated knockdown of genes in the flavoprotein signature led to decreased proliferation and migration of ESCC cells. Taken together, CTTN, GGH, GPD2, PYROXD2, SRC, and SYNJ2BP have an important clinical significance for prognosis of ESCC patients, suggesting they are efficient prognostic markers and potential targets for ESCC therapy.
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LncRNA profile study reveals a three-lncRNA signature associated with the survival of esophageal squamous cell carcinoma patients
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[19] array · 2 items
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SYNJ2BP-Homo-2746
[1]
GGACAAGUUGAAGACCCUUTT
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[0]
GGH-Homo-338
[1]
GCGAGCCUCGAGCUGUCUATT
[21] array · 2 items
[0]
GPD2-Homo-494
[1]
GCAUUUCAGAACCAGUUAATT
[22] array · 2 items
[0]
SRC-Homo-937
[1]
GCCUCUCAGUGUCUGACUUTT
[23] array · 2 items
[0]
Negative control
[1]
UUCUCCGAACGUGUCACGUTT
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section[7]/table-wrap[1]#tab2
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note
Identities of flavoproteins and their interacting proteins in the prognostic expression signature and their univariate Cox association with prognosis.
structure object · 5 fields
pmcid
PMC6878914
section_index
15
section_title
3.2. Selection of Flavoproteins and Interacting Protein Combinations for the Prognostic Signature in the Training Dataset
row_count
7
column_count
7
table object · 8 fields
label
Table 3
caption
Identities of flavoproteins and their interacting proteins in the prognostic expression signature and their univariate Cox association with prognosis.
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[0] array · 7 items
[0]
Ensembl ID
[1]
Gene symbol
[2]
Gene description
[3]
Coefficienta
[4]
P valuea
[5]
Gene expression level association with prognosis
[6]
Chromosome location
[1] array · 7 items
[0]
ENSG00000115159
[1]
GPD2
[2]
Glycerol-3-phosphate dehydrogenase 2
[3]
−0.77
[4]
0.01
[5]
Low
[6]
2 : 156435290–156613735 : 1
[2] array · 7 items
[0]
ENSG00000119943
[1]
PYROXD2
[2]
Pyridine nucleotide-disulphide oxidoreductase domain 2
[3]
0.28
[4]
0.00
[5]
High
[6]
10 : 98383565–98415184 : −1
[3] array · 7 items
[0]
ENSG00000085733
[1]
CTTN
[2]
Cortactin
[3]
0.33
[4]
0.00
[5]
High
[6]
11 : 70398404–70436584 : 1
[4] array · 7 items
[0]
ENSG00000137563
[1]
GGH
[2]
Gamma-glutamyl hydrolase
[3]
−0.39
[4]
0.01
[5]
Low
[6]
8 : 63015079–63039171 : −1
[5] array · 7 items
[0]
ENSG00000197122
[1]
SRC
[2]
Non-receptor tyrosine kinase
[3]
0.54
[4]
0.02
[5]
High
[6]
20 : 37344685–37406050 : 1
[6] array · 7 items
[0]
ENSG00000213463
[1]
SYNJ2BP
[2]
Synaptojanin 2 binding protein
[3]
0.48
[4]
0.02
[5]
High
[6]
14 : 70366496–70417061 : −1
locator
section[15]/table-wrap[1]#tab3
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asset:data:geo:GSE53625 not downloaded
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asset:data:geo:GSE53625 licence not read
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student_t
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Student's t test
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method-2
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survival_analysis
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kaplan_meier
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survival_km
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time_to_event_with_censoring
evidence object · 3 fields
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Kaplan-Meier
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method-3
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diagnostic_evaluation
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confusion_counts
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reference_standard_and_test
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method.student_t
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capability:computational_analysis
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gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
complete
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blocked_on
nothing:replicable_now
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method object · 5 fields
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false
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missing_operations array · 1 item
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student_t
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The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test.
capability object · 4 fields
tier
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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
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[0]
GSE53625
resolved_accessions array · 1 item
[0]
GSE53625
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No data were used to support this study.
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The paper names GSE53625 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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source:pmid:31815134
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asset:table:pmid:31815134:2
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asset:table:pmid:31815134:3
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data:geo:GSE53625
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partial
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extraction_review
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MiniMax-M3.1-Flash
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minimax
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minimax
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single_reader
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extraction
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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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pmid:31815134
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source:pmid:31815134
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PMID 31815134 full text
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data:geo:GSE53625
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GEO GSE53625
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paper
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pmid:31815134
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source:pmid:31815134
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PMID 31815134 full text
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data:geo:GSE53625
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GEO GSE53625
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data:geo:GSE53625
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agent:corpus-assay-engine
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data_generation
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transfection
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99e1195c7d6f
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[0]
=0.032, n = 121). Furthermore, RNAi-mediated knockdown of genes in the flavoprotein signature led t
[1]
4 h until 70–80% confluence. ESCC cells were transfected with 30 nM or 75 nM siRNA using Lipofectamin
[2]
C cells were transfected with 30 nM or 75 nM siRNA using Lipofectamine 3000 (Invitrogen) accord
[3]
SRC, and SYNJ2BP and a negative control (NC) siRNA were synthesized by GenePharma (Suzhou, Jian
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paper_text_order:1256
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However, their clinical significance and function in esophageal squamous cell carcinoma (ESCC) are little known. Here, using survival analysis and machine learning, we mined 179 patient expression profiles with ESCC in GSE53625 from the Gene Expression Omnibus (GEO) database and constructed a signature consisting of two flavoprotein genes (GPD2 and PYROXD2) and four flavoprotein interacting protein genes (CTTN, GGH, SRC, and SYNJ2BP). Kaplan-Meier analysis revealed the signature was significantly associated with the survival of ESCC patients (mean survival time: 26.77 months in the high-risk group vs. 54.97 months in the low-risk group, P < 0.001, n = 179), and time-dependent ROC analysis demonstrated that the six-gene signature had good predictive ability for six-year survival for ESCC (AUC = 0.86, 95% CI: 0.81-0.90). We then validated its prediction performance in an independent set by RT-PCR (mean survival: 15.73 months in the high-risk group vs. 21.1 months in the low-risk group, P=0.032, n = 121). Furthermore, RNAi-mediated knockdown of genes in the flavoprotein signature led to decreased proliferation and migration of ESCC cells. 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