Differentially Expressed Genes
Differentially expressed data illustrated that 1332 mRNA including 610 upregulated and 722 down-regulated were differentially expressed in ESCA. Furthermore, 98 lncRNAs including 49 upregulated and 49 down-regulated were indicated as deferentially expressed lncRNA in the patients. One hundred and one miRNAs including 62 up-regulated and 39 down-regulated demonstrated differential expression in the ESCA samples. The data are shown in Figs. 1, and Tables 2, 3.
Table 2. Top 20 up-regulated mRNAs, lncRNAs, and miRNAs
mRNA
|
|
|
|
|
|
|
|
|
symbol
|
logFC
|
AveExpr
|
t
|
PValue
|
FDR
|
B
|
ENSG00000128422
|
KRT17
|
4.77
|
8.62
|
3.69
|
0.00
|
0.00
|
-0.08
|
ENSG00000060718
|
COL11A1
|
4.66
|
2.33
|
3.45
|
0.00
|
0.01
|
-0.60
|
ENSG00000136231
|
IGF2BP3
|
4.63
|
3.32
|
4.22
|
0.00
|
0.00
|
1.99
|
ENSG00000123388
|
HOXC11
|
4.52
|
1.29
|
6.73
|
0.00
|
0.00
|
13.01
|
ENSG00000137745
|
MMP13
|
4.35
|
1.30
|
3.62
|
0.00
|
0.00
|
-0.08
|
ENSG00000149968
|
MMP3
|
4.31
|
3.62
|
3.69
|
0.00
|
0.00
|
0.16
|
ENSG00000180818
|
HOXC10
|
4.31
|
2.80
|
4.63
|
0.00
|
0.00
|
3.52
|
ENSG00000123500
|
COL10A1
|
4.30
|
2.90
|
3.45
|
0.00
|
0.01
|
-0.59
|
ENSG00000099953
|
MMP11
|
4.29
|
5.35
|
3.86
|
0.00
|
0.00
|
0.68
|
ENSG00000180806
|
HOXC9
|
4.29
|
1.10
|
8.60
|
0.00
|
0.00
|
22.99
|
ENSG00000262406
|
MMP12
|
4.24
|
4.08
|
4.16
|
0.00
|
0.00
|
1.75
|
ENSG00000037965
|
HOXC8
|
4.18
|
1.04
|
7.85
|
0.00
|
0.00
|
18.85
|
ENSG00000169429
|
CXCL8
|
4.11
|
4.99
|
4.04
|
0.00
|
0.00
|
1.30
|
ENSG00000123364
|
HOXC13
|
4.05
|
0.99
|
4.19
|
0.00
|
0.00
|
1.86
|
ENSG00000170373
|
CST1
|
4.01
|
3.24
|
3.22
|
0.00
|
0.01
|
-1.29
|
ENSG00000131015
|
ULBP2
|
3.95
|
2.24
|
5.91
|
0.00
|
0.00
|
9.01
|
ENSG00000127928
|
GNGT1
|
3.94
|
0.11
|
3.66
|
0.00
|
0.00
|
0.06
|
ENSG00000206075
|
SERPINB5
|
3.83
|
7.05
|
4.11
|
0.00
|
0.00
|
1.46
|
ENSG00000115008
|
IL1A
|
3.81
|
1.98
|
3.57
|
0.00
|
0.00
|
-0.23
|
ENSG00000164283
|
ESM1
|
3.80
|
1.81
|
5.99
|
0.00
|
0.00
|
9.38
|
LncRNA
|
|
|
|
|
|
|
|
|
symbol
|
logFC
|
AveExpr
|
t
|
PValue
|
FDR
|
B
|
ENSG00000228742
|
AC002384.1
|
4.21
|
0.43
|
5.23
|
0.00
|
0.00
|
6.00
|
ENSG00000268621
|
IGFL2-AS1
|
3.94
|
0.15
|
3.69
|
0.00
|
0.00
|
0.15
|
ENSG00000276850
|
AC245041.2
|
3.76
|
1.55
|
4.17
|
0.00
|
0.00
|
1.79
|
ENSG00000229970
|
AC007128.1
|
3.58
|
-0.70
|
4.76
|
0.00
|
0.00
|
4.05
|
ENSG00000281406
|
BLACAT1
|
3.39
|
1.85
|
4.77
|
0.00
|
0.00
|
4.10
|
ENSG00000204949
|
FAM83A-AS1
|
3.33
|
0.27
|
3.35
|
0.00
|
0.01
|
-0.90
|
ENSG00000273760
|
AC245041.1
|
3.31
|
0.49
|
3.41
|
0.00
|
0.01
|
-0.71
|
ENSG00000226476
|
LINC01748
|
3.24
|
0.38
|
4.18
|
0.00
|
0.00
|
1.85
|
ENSG00000249395
|
CASC9
|
3.12
|
2.04
|
3.37
|
0.00
|
0.01
|
-0.84
|
ENSG00000206195
|
DUXAP8
|
3.02
|
2.03
|
4.05
|
0.00
|
0.00
|
1.39
|
ENSG00000230061
|
TRPM2-AS
|
2.59
|
0.86
|
3.23
|
0.00
|
0.01
|
-1.25
|
ENSG00000259230
|
LINC02323
|
2.43
|
0.30
|
4.02
|
0.00
|
0.00
|
1.27
|
ENSG00000265415
|
AC099850.3
|
2.42
|
1.63
|
6.74
|
0.00
|
0.00
|
13.04
|
ENSG00000254560
|
BBOX1-AS1
|
2.38
|
1.52
|
3.94
|
0.00
|
0.00
|
1.00
|
ENSG00000172965
|
MIR4435-2HG
|
2.23
|
4.11
|
6.84
|
0.00
|
0.00
|
13.72
|
ENSG00000253669
|
AP003356.1
|
2.18
|
0.72
|
5.20
|
0.00
|
0.00
|
5.88
|
ENSG00000227403
|
LINC01806
|
2.17
|
1.49
|
3.31
|
0.00
|
0.01
|
-1.01
|
ENSG00000249859
|
PVT1
|
2.03
|
3.97
|
4.89
|
0.00
|
0.00
|
4.57
|
ENSG00000222041
|
CYTOR
|
2.03
|
3.11
|
5.99
|
0.00
|
0.00
|
9.49
|
ENSG00000261116
|
AL049555.1
|
1.92
|
4.31
|
3.45
|
0.00
|
0.01
|
-0.73
|
miRNA
|
|
|
|
|
|
|
|
|
|
logFC
|
AveExpr
|
t
|
PValue
|
FDR
|
B
|
hsa-miR-196a-5p
|
5.14
|
6.47
|
7.40
|
0.00
|
0.00
|
17.19
|
hsa-miR-196b-5p
|
4.16
|
7.36
|
7.62
|
0.00
|
0.00
|
18.42
|
hsa-miR-767-5p
|
3.94
|
2.12
|
2.70
|
0.01
|
0.02
|
-3.02
|
hsa-miR-944
|
3.75
|
3.80
|
2.46
|
0.01
|
0.04
|
-3.61
|
hsa-miR-105-5p
|
3.62
|
2.31
|
2.48
|
0.01
|
0.03
|
-3.55
|
hsa-miR-205-5p
|
3.40
|
9.25
|
2.46
|
0.01
|
0.04
|
-3.95
|
hsa-miR-1269a
|
3.21
|
2.45
|
2.11
|
0.04
|
0.07
|
-4.37
|
hsa-miR-135b-5p
|
2.96
|
5.08
|
5.31
|
0.00
|
0.00
|
6.33
|
hsa-miR-4652-5p
|
2.89
|
0.62
|
4.46
|
0.00
|
0.00
|
2.81
|
hsa-miR-224-5p
|
2.48
|
5.58
|
3.67
|
0.00
|
0.00
|
-0.37
|
hsa-miR-615-3p
|
2.25
|
0.78
|
4.69
|
0.00
|
0.00
|
3.72
|
hsa-miR-205-3p
|
2.18
|
0.01
|
2.83
|
0.01
|
0.02
|
-2.67
|
hsa-miR-452-3p
|
2.09
|
1.75
|
3.09
|
0.00
|
0.01
|
-1.94
|
hsa-miR-937-3p
|
2.03
|
0.70
|
4.38
|
0.00
|
0.00
|
2.50
|
hsa-miR-431-5p
|
1.99
|
0.17
|
4.85
|
0.00
|
0.00
|
4.40
|
hsa-miR-181b-3p
|
1.98
|
2.55
|
5.92
|
0.00
|
0.00
|
9.32
|
hsa-miR-4746-5p
|
1.97
|
1.96
|
5.57
|
0.00
|
0.00
|
7.62
|
hsa-miR-135b-3p
|
1.94
|
0.32
|
4.21
|
0.00
|
0.00
|
1.82
|
hsa-miR-452-5p
|
1.79
|
6.23
|
3.46
|
0.00
|
0.00
|
-1.08
|
hsa-miR-675-3p
|
1.71
|
3.24
|
2.34
|
0.02
|
0.05
|
-3.98
|
Table 3. Top 20 down-regulated mRNAs, lncRNAs, and miRNAs
mRNA
|
|
|
|
|
|
|
|
|
symbol
|
logFC
|
AveExpr
|
t
|
PValue
|
FDR
|
B
|
ENSG00000096088
|
PGC
|
-9.90
|
1.58
|
-7.95
|
0.00
|
0.00
|
19.92
|
ENSG00000168631
|
DPCR1
|
-6.40
|
1.02
|
-7.60
|
0.00
|
0.00
|
17.91
|
ENSG00000184956
|
MUC6
|
-6.08
|
2.13
|
-6.17
|
0.00
|
0.00
|
10.30
|
ENSG00000167653
|
PSCA
|
-5.90
|
3.12
|
-8.23
|
0.00
|
0.00
|
21.56
|
ENSG00000019102
|
VSIG2
|
-5.25
|
1.84
|
-8.64
|
0.00
|
0.00
|
23.99
|
ENSG00000196188
|
CTSE
|
-5.07
|
2.69
|
-4.47
|
0.00
|
0.00
|
2.60
|
ENSG00000215182
|
MUC5AC
|
-5.03
|
2.86
|
-4.65
|
0.00
|
0.00
|
3.34
|
ENSG00000115386
|
REG1A
|
-4.81
|
1.67
|
-4.14
|
0.00
|
0.00
|
1.35
|
ENSG00000160182
|
TFF1
|
-4.81
|
1.65
|
-4.73
|
0.00
|
0.00
|
3.70
|
ENSG00000134240
|
HMGCS2
|
-4.80
|
0.95
|
-5.25
|
0.00
|
0.00
|
5.97
|
ENSG00000112936
|
C7
|
-4.54
|
1.11
|
-7.29
|
0.00
|
0.00
|
16.22
|
ENSG00000109906
|
ZBTB16
|
-4.45
|
0.54
|
-8.59
|
0.00
|
0.00
|
23.63
|
ENSG00000174514
|
MFSD4A
|
-4.43
|
2.79
|
-8.94
|
0.00
|
0.00
|
25.79
|
ENSG00000168079
|
SCARA5
|
-4.30
|
0.20
|
-7.44
|
0.00
|
0.00
|
17.04
|
ENSG00000066405
|
CLDN18
|
-4.24
|
3.86
|
-3.84
|
0.00
|
0.00
|
0.24
|
ENSG00000125144
|
MT1G
|
-4.23
|
3.14
|
-8.73
|
0.00
|
0.00
|
24.52
|
ENSG00000163884
|
KLF15
|
-4.18
|
0.38
|
-9.84
|
0.00
|
0.00
|
31.17
|
ENSG00000170011
|
MYRIP
|
-4.16
|
0.14
|
-9.12
|
0.00
|
0.00
|
26.77
|
ENSG00000180875
|
GREM2
|
-4.14
|
0.10
|
-7.52
|
0.00
|
0.00
|
17.47
|
ENSG00000139874
|
SSTR1
|
-4.07
|
0.26
|
-4.82
|
0.00
|
0.00
|
4.19
|
LncRNA
|
|
|
|
|
|
|
|
|
symbol
|
logFC
|
AveExpr
|
t
|
PValue
|
FDR
|
B
|
ENSG00000241388
|
HNF1A-AS1
|
-3.02
|
1.24
|
-3.24
|
0.00
|
0.01
|
-1.51
|
ENSG00000254343
|
AC091563.1
|
-2.97
|
0.09
|
-6.23
|
0.00
|
0.00
|
10.67
|
ENSG00000259291
|
ZNF710-AS1
|
-2.97
|
2.31
|
-11.47
|
0.00
|
0.00
|
41.54
|
ENSG00000203709
|
C1orf132
|
-2.93
|
1.77
|
-9.43
|
0.00
|
0.00
|
28.67
|
ENSG00000250742
|
LINC02381
|
-2.68
|
2.18
|
-6.90
|
0.00
|
0.00
|
14.14
|
ENSG00000260912
|
AL158206.1
|
-2.24
|
2.63
|
-6.94
|
0.00
|
0.00
|
14.31
|
ENSG00000268388
|
FENDRR
|
-2.17
|
2.25
|
-4.87
|
0.00
|
0.00
|
4.40
|
ENSG00000272894
|
AC004982.2
|
-2.12
|
0.66
|
-4.56
|
0.00
|
0.00
|
3.21
|
ENSG00000227218
|
AL157935.1
|
-2.05
|
0.28
|
-4.92
|
0.00
|
0.00
|
4.69
|
ENSG00000196167
|
COLCA1
|
-1.98
|
2.77
|
-3.42
|
0.00
|
0.01
|
-1.03
|
ENSG00000224078
|
SNHG14
|
-1.96
|
3.00
|
-4.53
|
0.00
|
0.00
|
2.95
|
ENSG00000249669
|
CARMN
|
-1.76
|
1.78
|
-3.75
|
0.00
|
0.00
|
0.22
|
ENSG00000180769
|
WDFY3-AS2
|
-1.70
|
0.29
|
-6.59
|
0.00
|
0.00
|
12.44
|
ENSG00000188242
|
PP7080
|
-1.64
|
4.99
|
-3.81
|
0.00
|
0.00
|
0.12
|
ENSG00000277496
|
AL357033.4
|
-1.59
|
1.04
|
-3.73
|
0.00
|
0.00
|
0.20
|
ENSG00000260461
|
AL133355.1
|
-1.54
|
1.14
|
-6.53
|
0.00
|
0.00
|
12.16
|
ENSG00000180139
|
ACTA2-AS1
|
-1.49
|
0.34
|
-3.72
|
0.00
|
0.00
|
0.19
|
ENSG00000251615
|
AC104825.2
|
-1.48
|
1.56
|
-4.48
|
0.00
|
0.00
|
2.91
|
ENSG00000261338
|
AC021016.2
|
-1.48
|
0.14
|
-6.76
|
0.00
|
0.00
|
13.28
|
ENSG00000225302
|
AC023283.1
|
-1.48
|
1.22
|
-3.57
|
0.00
|
0.00
|
-0.34
|
miRNA
|
|
|
|
|
|
|
|
|
|
logFC
|
AveExpr
|
t
|
PValue
|
FDR
|
B
|
hsa-miR-204-5p
|
-3.91
|
0.51
|
-8.58
|
0.00
|
0.00
|
24.23
|
hsa-miR-375
|
-3.71
|
11.09
|
-3.90
|
0.00
|
0.00
|
0.35
|
hsa-miR-133a-3p
|
-2.98
|
4.07
|
-5.24
|
0.00
|
0.00
|
5.86
|
hsa-miR-1-3p
|
-2.63
|
4.72
|
-4.30
|
0.00
|
0.00
|
1.87
|
hsa-miR-133b
|
-2.39
|
0.64
|
-4.59
|
0.00
|
0.00
|
3.17
|
hsa-miR-129-5p
|
-2.38
|
1.30
|
-5.62
|
0.00
|
0.00
|
7.72
|
hsa-miR-1468-5p
|
-2.25
|
1.67
|
-7.11
|
0.00
|
0.00
|
15.49
|
hsa-miR-139-5p
|
-2.03
|
5.22
|
-7.48
|
0.00
|
0.00
|
17.60
|
hsa-miR-29b-2-5p
|
-2.02
|
4.15
|
-8.54
|
0.00
|
0.00
|
23.98
|
hsa-miR-148a-3p
|
-1.95
|
14.33
|
-6.52
|
0.00
|
0.00
|
12.20
|
hsa-miR-30a-3p
|
-1.93
|
10.62
|
-6.16
|
0.00
|
0.00
|
10.35
|
hsa-miR-29c-3p
|
-1.89
|
10.36
|
-6.05
|
0.00
|
0.00
|
9.79
|
hsa-miR-30a-5p
|
-1.87
|
13.23
|
-5.98
|
0.00
|
0.00
|
9.41
|
hsa-miR-145-5p
|
-1.78
|
11.00
|
-4.35
|
0.00
|
0.00
|
2.06
|
hsa-miR-338-5p
|
-1.75
|
2.04
|
-4.92
|
0.00
|
0.00
|
4.52
|
hsa-miR-378c
|
-1.74
|
3.04
|
-6.49
|
0.00
|
0.00
|
12.09
|
hsa-miR-145-3p
|
-1.62
|
5.36
|
-4.17
|
0.00
|
0.00
|
1.36
|
hsa-miR-338-3p
|
-1.56
|
9.42
|
-4.19
|
0.00
|
0.00
|
1.43
|
hsa-miR-29c-5p
|
-1.55
|
3.70
|
-7.52
|
0.00
|
0.00
|
17.83
|
hsa-miR-139-3p
|
-1.47
|
3.00
|
-4.79
|
0.00
|
0.00
|
3.90
|
GO enrichment and KEGG pathway analysis
Thereby GO enrichment analysis, we indicated several prominent roles of the DEmRNAs, Biological process of GO illustrated that the DEmRNAs are majorly assigned to DNA replication, mitotic nuclear division, organelle fission, chromosome segregation, and sister chromatid segregation.Also, the cellular component of GO depicted that the genes were significantly classified inthe chromosomal region, condensed chromosome, spindle, collagen-containing, and extracellular matrix. Moreover, the GO molecular function part showed that the DEmRNAs dominantly enriched in extracellular matrix structural constituent, DNA helicase activity, catalytic activity, acting on DNA, single-stranded DNA-dependent ATP-dependent DNA helicase activity, and DNA replication origin binding (Fig 2).Furthermore, KEGG pathway analysis showed that the DEmRNAs remarkably attributed to Cell cycle, DNA replication, p53 signaling pathway, AGE-RAGE signaling pathway in diabetic, and PPAR signaling pathway (fig 3).
protein-protein interaction (PPI) network construction
For better understanding of the protein-protein interactions, we constructed a PPI network of the DEmRNAs via the STRING database. The data showed that IGFBP5, ACAN, ADAMTS12, MMP13, and CDH2 were the important PPI hubs (Fig 4)
LncRNA-miRNA-mRNA ceRNA network construction
Based on the competing endogens RNA (ceRNA) hypothesis, which explains that lncRNAs regulate mRNA expression level by competing the shared miRNAs in cells, a ceRNA network was built based on the differentially expressed genes data via starbase database in R software. The nodes and edges were visualizedbyCytoscape 3.7.2. The ceRNA network data demonstrated critical lncRNAs includingTMEM16B-AS1, AC093010.3, SNHG3, and PVT1 which have an important role in the development of ESCA(Fig. 5).
Kaplan-Meier survival analysis of differentially expressed genes
To explore the association of differential expression of the genes and the ESCApatient’s prognosis, Kaplan-Meier survival analysis was conducted over the differentially expressed genes. The data indicated that 41 mRNAs, 5 lncRNAs, and 23 miRNAs were associated with the overall survival rate in the patients. The top 20 hits of each group are presented in Table 4.
Table 4. Top 20 mRNAs, lncRNAs, and miRNAs that were associated with overall survival.
mRNA
|
|
|
|
|
|
|
symbol
|
HR
|
lower95
|
upper95
|
pValue
|
ENSG00000091879
|
ANGPT2
|
2.10
|
1.28
|
3.46
|
0.00
|
ENSG00000146386
|
ABRACL
|
2.10
|
1.27
|
3.45
|
0.00
|
ENSG00000168298
|
HIST1H1E
|
1.90
|
1.15
|
3.13
|
0.01
|
ENSG00000130208
|
APOC1
|
1.89
|
1.15
|
3.11
|
0.01
|
ENSG00000121769
|
FABP3
|
1.76
|
1.08
|
2.88
|
0.02
|
ENSG00000164283
|
ESM1
|
1.72
|
1.05
|
2.82
|
0.03
|
ENSG00000130826
|
DKC1
|
1.66
|
1.01
|
2.72
|
0.04
|
ENSG00000180818
|
HOXC10
|
1.66
|
1.02
|
2.71
|
0.04
|
ENSG00000040275
|
SPDL1
|
1.64
|
1.00
|
2.69
|
0.04
|
ENSG00000105486
|
LIG1
|
1.64
|
1.00
|
2.70
|
0.04
|
ENSG00000153310
|
FAM49B
|
1.64
|
1.00
|
2.68
|
0.04
|
ENSG00000124731
|
TREM1
|
1.61
|
0.97
|
2.67
|
0.05
|
ENSG00000126709
|
IFI6
|
0.62
|
0.38
|
1.01
|
0.05
|
ENSG00000148180
|
GSN
|
0.61
|
0.37
|
1.00
|
0.05
|
ENSG00000175287
|
PHYHD1
|
0.61
|
0.37
|
1.00
|
0.05
|
ENSG00000149582
|
TMEM25
|
0.61
|
0.37
|
0.99
|
0.05
|
ENSG00000128340
|
RAC2
|
0.61
|
0.37
|
0.99
|
0.05
|
ENSG00000137198
|
GMPR
|
0.61
|
0.37
|
0.99
|
0.04
|
ENSG00000182568
|
SATB1
|
0.60
|
0.36
|
1.00
|
0.04
|
ENSG00000090006
|
LTBP4
|
0.60
|
0.37
|
0.98
|
0.04
|
LncRNA
|
|
|
|
|
|
|
symbol
|
HR
|
lower95
|
upper95
|
pValue
|
ENSG00000180769
|
WDFY3-AS2
|
0.51
|
0.31
|
0.85
|
0.01
|
ENSG00000253669
|
AP003356.1
|
1.66
|
1.01
|
2.74
|
0.03
|
ENSG00000229970
|
AC007128.1
|
1.65
|
1.01
|
2.70
|
0.05
|
ENSG00000259366
|
AC108449.2
|
0.52
|
0.32
|
0.86
|
0.01
|
ENSG00000231607
|
DLEU2
|
1.70
|
1.04
|
2.80
|
0.03
|
miRNA
|
|
|
|
|
|
|
symbol
|
HR
|
lower95
|
upper95
|
pValue
|
hsa-miR-29c-3p
|
0.56
|
0.36
|
0.88
|
0.01
|
hsa-miR-181b-3p
|
1.61
|
1.03
|
2.51
|
0.04
|
hsa-miR-550a-3p
|
1.73
|
1.10
|
2.70
|
0.02
|
hsa-miR-3682-3p
|
1.71
|
1.09
|
2.68
|
0.02
|
hsa-miR-101-3p
|
0.61
|
0.39
|
0.97
|
0.03
|
hsa-miR-27a-3p
|
0.59
|
0.38
|
0.92
|
0.02
|
hsa-miR-23a-3p
|
0.59
|
0.38
|
0.92
|
0.02
|
hsa-miR-99a-5p
|
0.58
|
0.37
|
0.91
|
0.02
|
hsa-miR-1249-3p
|
0.64
|
0.41
|
1.00
|
0.05
|
hsa-miR-425-5p
|
1.96
|
1.25
|
3.08
|
0.00
|
hsa-miR-323b-3p
|
1.72
|
1.09
|
2.69
|
0.02
|
hsa-miR-1269a
|
1.56
|
0.99
|
2.47
|
0.04
|
hsa-miR-6842-3p
|
0.62
|
0.40
|
0.97
|
0.04
|
hsa-miR-151a-3p
|
0.63
|
0.40
|
0.98
|
0.04
|
hsa-let-7b-3p
|
0.56
|
0.36
|
0.88
|
0.01
|
hsa-let-7a-5p
|
0.55
|
0.35
|
0.87
|
0.01
|
hsa-miR-412-5p
|
0.60
|
0.39
|
0.95
|
0.03
|
hsa-let-7a-3p
|
0.57
|
0.37
|
0.89
|
0.01
|
hsa-miR-33a-3p
|
0.58
|
0.37
|
0.91
|
0.02
|
hsa-miR-31-3p
|
0.63
|
0.40
|
0.99
|
0.04
|
Diagnostic value analysisof differentially expressed lncRNAs
For demonstrating the diagnostic value of each DElncRNAs, AUC curve analysis was accomplished in the ESCA samples. All 98 DElncRNAs indicated remarkable diagnostic values in the patients. The top 30 hits of the lncRNAs are presented in Table 5.
Table 5. Top 20 lncRNAs that had remarkable diagnostic value.
lncRNA
|
AUC
|
SE
|
p-value
|
Lower (95%CI)
|
Upper (95%CI)
|
expression
|
MIR4435-2HG
|
0.99
|
0.007
|
0
|
0.977
|
1
|
Up
|
CYTOR
|
0.977
|
0.013
|
0
|
0.951
|
1
|
Up
|
AP003356.1
|
0.955
|
0.033
|
0
|
0.891
|
1
|
Up
|
PVT1
|
0.951
|
0.024
|
0
|
0.905
|
0.997
|
Up
|
C1orf132
|
0.941
|
0.031
|
0
|
0
|
0.12
|
Down
|
MAFG-AS1
|
0.94
|
0.035
|
0
|
0.872
|
1
|
Up
|
AL158212.3
|
0.936
|
0.046
|
0
|
0
|
0.155
|
Down
|
DLEU2
|
0.928
|
0.026
|
0
|
0.877
|
0.98
|
Up
|
ZNF710-AS1
|
0.926
|
0.039
|
0
|
0
|
0.151
|
Down
|
AC021016.2
|
0.924
|
0.04
|
0
|
0
|
0.155
|
Down
|
AL133355.1
|
0.919
|
0.039
|
0
|
0.004
|
0.159
|
Down
|
MELTF-AS1
|
0.916
|
0.035
|
0
|
0.848
|
0.984
|
Up
|
BLACAT1
|
0.911
|
0.029
|
0
|
0.854
|
0.969
|
Up
|
AC002384.1
|
0.909
|
0.035
|
0
|
0.84
|
0.978
|
Up
|
AC099850.3
|
0.906
|
0.053
|
0
|
0.802
|
1
|
Up
|
AC092718.4
|
0.903
|
0.052
|
0
|
0.8
|
1
|
Up
|
TYMSOS
|
0.901
|
0.041
|
0
|
0.82
|
0.981
|
Up
|
AC091563.1
|
0.901
|
0.044
|
0
|
0.014
|
0.185
|
Down
|
TMPO-AS1
|
0.899
|
0.031
|
0
|
0.839
|
0.96
|
Up
|
AC026401.3
|
0.898
|
0.04
|
0
|
0.82
|
0.977
|
Up
|
Potential diagnostic and prognostic lncRNA
Thereby merging the diagnostic (AUC value) and prognostic (HR) values of the LncRNAs in the ESCA patients, potential novel lncRNA biomarkers were retrieved. The summary of the data is presented in table 6. The data demonstrated that the lncRNA WDFY3-AS2, AC108449.2,DLEU2, AC007128.1,and AP003356.1 as potential diagnostic and prognostic biomarker in the ESCApatients (Figure 6).
Table 6. Merge diagnostic and prognostic data of the LncRNAs.
symbol
|
HR
|
lower95
|
upper95
|
pValue
|
AUC
|
SE
|
p-value
|
Lower (95%CI)
|
Upper (95%CI)
|
expression
|
WDFY3-AS2
|
0.514
|
0.313
|
0.846
|
0.006
|
0.885
|
0.062
|
0.000
|
0.000
|
0.236
|
Down
|
AC108449.2
|
0.524
|
0.318
|
0.863
|
0.007
|
0.842
|
0.051
|
0.000
|
0.058
|
0.257
|
Down
|
DLEU2
|
1.702
|
1.035
|
2.799
|
0.029
|
0.928
|
0.026
|
0.000
|
0.877
|
0.980
|
Up
|
AP003356.1
|
1.661
|
1.005
|
2.744
|
0.034
|
0.955
|
0.033
|
0.000
|
0.891
|
1.000
|
Up
|
AC007128.1
|
1.654
|
1.013
|
2.700
|
0.046
|
0.854
|
0.063
|
0.000
|
0.731
|
0.977
|
Up
|
UGDH-AS1
|
0.645
|
0.395
|
1.053
|
0.077
|
0.827
|
0.083
|
0.000
|
0.011
|
0.335
|
Down
|
TMEM161B-AS1
|
1.478
|
0.905
|
2.416
|
0.114
|
0.862
|
0.061
|
0.000
|
0.019
|
0.257
|
Down
|
CD44-AS1
|
1.412
|
0.853
|
2.337
|
0.153
|
0.804
|
0.067
|
0.001
|
0.672
|
0.936
|
Up
|
AGAP2-AS1
|
0.707
|
0.433
|
1.154
|
0.164
|
0.853
|
0.060
|
0.000
|
0.734
|
0.971
|
Up
|
LINC00511
|
1.396
|
0.852
|
2.290
|
0.173
|
0.843
|
0.064
|
0.000
|
0.717
|
0.969
|
Up
|
AC122129.1
|
0.721
|
0.440
|
1.179
|
0.182
|
0.824
|
0.060
|
0.000
|
0.058
|
0.294
|
Down
|
AL357033.4
|
1.387
|
0.849
|
2.266
|
0.193
|
0.804
|
0.059
|
0.001
|
0.081
|
0.311
|
Down
|
AL133355.1
|
0.731
|
0.447
|
1.196
|
0.202
|
0.919
|
0.039
|
0.000
|
0.004
|
0.159
|
Down
|
FOXD2-AS1
|
1.374
|
0.841
|
2.243
|
0.205
|
0.827
|
0.091
|
0.000
|
0.648
|
1.000
|
Up
|
AC004803.1
|
0.728
|
0.446
|
1.190
|
0.208
|
0.780
|
0.070
|
0.002
|
0.084
|
0.357
|
Down
|
AC099850.3
|
0.735
|
0.450
|
1.201
|
0.210
|
0.906
|
0.053
|
0.000
|
0.802
|
1.000
|
Up
|
AC022211.2
|
0.735
|
0.450
|
1.203
|
0.214
|
0.863
|
0.048
|
0.000
|
0.769
|
0.956
|
Up
|
CASC9
|
1.338
|
0.818
|
2.187
|
0.239
|
0.822
|
0.064
|
0.000
|
0.695
|
0.948
|
Up
|
LINC01572
|
1.325
|
0.811
|
2.164
|
0.255
|
0.785
|
0.097
|
0.002
|
0.595
|
0.974
|
Up
|
TSC22D1-AS1
|
0.754
|
0.462
|
1.231
|
0.255
|
0.862
|
0.044
|
0.000
|
0.053
|
0.224
|
Down
|