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pmid:33216732

Oncostatin M expression and TP53 mutation status regulate tumor-infiltration of immune cells and survival outcomes in cholangiocarcinoma.

Qi Liu · Tian Lan · Yuxuan Song · Jianpeng Cai · Xi Yu · Wei Chen

Aging · 2020 doi:10.18632/aging.103936

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complete

Experiment

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Data

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Analysis

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title
Oncostatin M expression and TP53 mutation status regulate tumor-infiltration of immune cells and survival outcomes in cholangiocarcinoma.
doi
10.18632/aging.103936
pmid
33216732
authors array · 6 items
[0]
Qi Liu
[1]
Tian Lan
[2]
Yuxuan Song
[3]
Jianpeng Cai
[4]
Xi Yu
[5]
Wei Chen
journal
Aging
year
2020
abstract
In this study, we used bioinformatics tools to analyze transcriptome data from cholangiocarcinoma (CCA) patients in multiple datasets (Sun Yat-sen University, TCGA and GSE32225 cohorts) to identify mechanisms that regulate tumor infiltration by immune cells and survival outcomes. We identified 96 differentially expressed genes (DEGs), including 13 upregulated and 83 downregulated genes, in CCA tissues as regulatory T cells were significantly higher and the proportions of activated natural killer cells and monocytes were significantly lower in CCA tissues than the precancerous tissues. The survival outcomes of CCA patients were associated with the TP53 gene mutation status, levels of Oncostatin M (OSM) expression, and the proportions of tumor-infiltrating immune cell types, including dendritic cells, monocytes, and T follicular helper cells. Functional enrichment analysis of the DEGs in the high OSM-expressing CCA tissues showed that pathways related to tumor progression and immune response were significantly upregulated. Our study demonstrates that OSM expression and TP53 mutation status regulate the tumor infiltration by immune cells and survival outcomes in CCA. OSM is thus a potential prognostic biomarker and therapeutic target in cholangiocarcinoma.
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Kaplan-Meier survival curve analysis and log-rank test showed that overall survival was significantly shorter for CCA patients with low OSM expression (OSMlow group) compared to those in the OSMhighgroup (Figure 5D).
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methodological
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sections[7] "Prognostic significance of OSM expression in CCA Patients with and without TP53 gene mutations" paragraph 2
quote
Kaplan-Meier survival curve analysis and log-rank test showed that overall survival was significantly shorter for CCA patients with low OSM expression (OSMlow group) compared to those in the OSMhighgroup (Figure 5D).
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We obtained transcriptome data from the TCGA database that included 9 precancerous and 36 CCA tissue samples
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sections[14] "CCA patient datasets" paragraph 3
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We obtained transcriptome data from the TCGA database that included 9 precancerous and 36 CCA tissue samples
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Gene-expression profiles of formalin-fixed, paraffin-embedded human intrahepatic cholangiocarcinoma
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Correlation between OSM expression and clinical characteristics in 203 CCA patients by chi-square test.
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OSM expression is an independent predictor of prognosis in CCA patients
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Table 1
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Correlation between OSM expression and clinical characteristics in 203 CCA patients by chi-square test.
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[0]
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High (n=101)
[2]
Low (n=102)
[3]
P
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[0]
Gender
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[2]
[3]
0.723
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[0]
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>58
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50
[2]
46
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≤58
[1]
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[2]
56
[3]
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[2]
[3]
0.726
[8] array · 4 items
[0]
>5cm
[1]
50
[2]
53
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51
[2]
49
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[2]
[3]
0.834
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21
[2]
20
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[1]
80
[2]
82
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[14] array · 4 items
[0]
single
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[2]
67
[3]
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[2]
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[0]
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[1]
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[2]
51
[3]
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[0]
complete
[1]
61
[2]
51
[3]
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[0]
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[1]
[2]
[3]
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[20] array · 4 items
[0]
>37 U/L
[1]
55
[2]
57
[3]
[21] array · 4 items
[0]
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[1]
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[2]
45
[3]
[22] array · 4 items
[0]
CA125
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[2]
[3]
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[23] array · 4 items
[0]
>35 U/mL
[1]
32
[2]
33
[3]
[24] array · 4 items
[0]
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[1]
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[2]
69
[3]
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[0]
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[2]
[3]
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[26] array · 4 items
[0]
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[1]
34
[2]
34
[3]
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[1]
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[2]
68
[3]
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69
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[1]
29
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72
[2]
52
[3]
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[2]
[3]
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[37] array · 4 items
[0]
YES
[1]
16
[2]
28
[3]
[38] array · 4 items
[0]
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[1]
85
[2]
74
[3]
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[0]
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[2]
[3]
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[40] array · 4 items
[0]
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[1]
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[2]
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[3]
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[0]
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[1]
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[2]
75
[3]
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[0]
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[3]
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[0]
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[1]
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[2]
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[3]
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[2]
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[3]
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Univariate and multivariate Cox analysis of potential prognostic factors in 203 CCA patients.
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OSM expression is an independent predictor of prognosis in CCA patients
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Univariate and multivariate Cox analysis of potential prognostic factors in 203 CCA patients.
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[0] array · 6 items
[0]
[1]
OS
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[3]
[4]
RFS
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[4]
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[4] array · 6 items
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[4]
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[5]
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[5] array · 6 items
[0]
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[1]
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[4]
1.435(1.034-1.993)
[5]
0.031
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[2]
0.000
[3]
[4]
2.171(1.542-3.058)
[5]
0.000
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[0]
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[2]
0.000
[3]
[4]
0.652(0.468-0.906)
[5]
0.011
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[0]
CA199(>37 U/L versus ≤ 37 U/L)
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[2]
0.000
[3]
[4]
1.468(1.053-2.046)
[5]
0.023
[9] array · 6 items
[0]
CA125 (>35 U/mL versus ≤35 U/mL)
[1]
1.995(1.402-2.839)
[2]
0.000
[3]
[4]
2.121(1.511-2.975)
[5]
0.000
[10] array · 6 items
[0]
CEA (>5μg/L versus ≤ 5μg/L)
[1]
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[2]
0.002
[3]
[4]
1.636(1.164-2.298)
[5]
0.005
[11] array · 6 items
[0]
Stage (IV+III+II versus I)
[1]
3.009(1.992-4.545)
[2]
0.000
[3]
[4]
2.875(1.955-4.227)
[5]
0.000
[12] array · 6 items
[0]
Lymphatic metastasis (yes versus no)
[1]
2.507(1.765-3.561)
[2]
0.000
[3]
[4]
2.119(1.517-2.961)
[5]
0.000
[13] array · 6 items
[0]
Distant metastasis (yes versus no)
[1]
1.934(1.298-2.880)
[2]
0.001
[3]
[4]
2.279(1.560-3.331)
[5]
0.000
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[1]
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[2]
0.000
[3]
[4]
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[5]
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[15] array · 6 items
[0]
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[1]
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[2]
0.001
[3]
[4]
0.644(0.463-0.896)
[5]
0.009
[16] array · 6 items
[0]
Liver cirrhosis (yes versus no)
[1]
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[2]
0.061
[3]
[4]
0.805(0.526-1.231)
[5]
0.316
[17] array · 6 items
[0]
Multivariate COX analysis
[1]
[2]
[3]
[4]
[5]
[18] array · 6 items
[0]
Tumor number (multiple versus single)
[1]
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[2]
0.020
[3]
[4]
1.655(1.115-2.457)
[5]
0.012
[19] array · 6 items
[0]
Tumor encapsulation (complete versus none)
[1]
0.626(0.425-0.922)
[2]
0.018
[3]
[4]
0.731(0.509-1.049)
[5]
0.089
[20] array · 6 items
[0]
CA125 (>35 U/mL versus ≤35 U/mL)
[1]
1.322(0.888-1.968)
[2]
0.169
[3]
[4]
1.595(1.099-2.316)
[5]
0.014
[21] array · 6 items
[0]
CA199(>37 U/L versus ≤ 37 U/L)
[1]
1.519(1.037-2.226)
[2]
0.032
[3]
[4]
1.100(0.774-1.563)
[5]
0.594
[22] array · 6 items
[0]
CEA (>5μg/L versus ≤ 5μg/L)
[1]
1.300(0.868-1.948)
[2]
0.203
[3]
[4]
1.146(0.783-1.676)
[5]
0.483
[23] array · 6 items
[0]
Stage (IV+III+II versus I)
[1]
1.534(0.891-2.672)
[2]
0.121
[3]
[4]
1.770(1.063-2.947)
[5]
0.028
[24] array · 6 items
[0]
Lymphatic metastasis (yes versus no)
[1]
1.432(0.904-2.270)
[2]
0.126
[3]
[4]
1.194(0.771-1.850)
[5]
0.427
[25] array · 6 items
[0]
Distant metastasis (yes versus no)
[1]
0.921(0.582-1.457)
[2]
0.724
[3]
[4]
1.375(0.878-2.154)
[5]
0.164
[26] array · 6 items
[0]
Vascular invasion (yes versus no)
[1]
1.160(0.733-1.835)
[2]
0.527
[3]
[4]
0.978(0.618-1.549)
[5]
0.926
[27] array · 6 items
[0]
OSM (high versus low)
[1]
0.541(0.372-0.787)
[2]
0.001
[3]
[4]
0.745(0.518-1.073)
[5]
0.114
locator
section[8]/table-wrap[2]#t2
[4] object · 16 fields
id
asset:table:pmid:33216732:3
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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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sha256:9d2e63dfeafb4cca787384acc4d4235cbe412507b36420da6303e300aefbc9a7
bytes
1792
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read_table
reader_status
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identifier
section[9]/table-wrap[1]#t3
version
null
note
Correlations between OSM and related genes and markers of immune cells in TIMER by spearman analysis.
structure object · 5 fields
pmcid
PMC11623973
section_index
9
section_title
OSM expression correlates with tumor infiltration of immune cells in CCA tissues
row_count
39
column_count
6
table object · 8 fields
label
Table 3
caption
Correlations between OSM and related genes and markers of immune cells in TIMER by spearman analysis.
rows array · 39 items
[0] array · 4 items
[0]
Cell type
[1]
Gene marker
[2]
None
[3]
Purity
[1] array · 6 items
[0]
[1]
[2]
Cor
[3]
P
[4]
Cor
[5]
P
[2] array · 6 items
[0]
B cell
[1]
CD19
[2]
-0.084
[3]
0.631
[4]
-0.414
[5]
0.012
[3] array · 6 items
[0]
[1]
CD22
[2]
0.233
[3]
0.177
[4]
-
[5]
-
[4] array · 6 items
[0]
[1]
CD70
[2]
0.248
[3]
0.151
[4]
-
[5]
-
[5] array · 6 items
[0]
CD8+T Cell
[1]
CD8A
[2]
0.144
[3]
0.409
[4]
-
[5]
-
[6] array · 6 items
[0]
[1]
CD8B
[2]
0.042
[3]
0.811
[4]
-
[5]
-
[7] array · 6 items
[0]
Tfh
[1]
IL21
[2]
0.008
[3]
0.964
[4]
-
[5]
-
[8] array · 6 items
[0]
[1]
ICOS
[2]
0.355
[3]
0.037
[4]
-
[5]
-
[9] array · 6 items
[0]
[1]
BCL-6
[2]
0.340
[3]
0.046
[4]
-
[5]
-
[10] array · 6 items
[0]
Thl
[1]
IL12RB2
[2]
0.228
[3]
0.188
[4]
-
[5]
-
[11] array · 6 items
[0]
[1]
T-bet (TBX21)
[2]
0.085
[3]
0.628
[4]
[5]
[12] array · 6 items
[0]
[1]
IFN-γ (IFNG)
[2]
0.117
[3]
0.505
[4]
[5]
[13] array · 6 items
[0]
[1]
TNF-α (TNF)
[2]
0.219
[3]
0.207
[4]
[5]
[14] array · 6 items
[0]
Th2
[1]
GATA3
[2]
0.159
[3]
0.363
[4]
[5]
[15] array · 6 items
[0]
[1]
STAT5A
[2]
0.120
[3]
0.493
[4]
[5]
[16] array · 6 items
[0]
[1]
IL13
[2]
-0.259
[3]
0.133
[4]
[5]
[17] array · 6 items
[0]
Th17
[1]
IL17A
[2]
0.294
[3]
0.087
[4]
-
[5]
-
[18] array · 6 items
[0]
[1]
STAT3
[2]
0.153
[3]
0.380
[4]
-
[5]
-
[19] array · 6 items
[0]
Treg
[1]
FOXP3
[2]
0.298
[3]
0.082
[4]
[5]
[20] array · 6 items
[0]
[1]
CCR8
[2]
0.204
[3]
0.240
[4]
[5]
[21] array · 6 items
[0]
[1]
STAT5B
[2]
0.148
[3]
0.396
[4]
[5]
[22] array · 6 items
[0]
[1]
TGFβ (TGFB1)
[2]
0.173
[3]
0.321
[4]
-
[5]
-
[23] array · 6 items
[0]
TAM
[1]
CCL2
[2]
0.289
[3]
0.092
[4]
-
[5]
-
[24] array · 6 items
[0]
[1]
CD68
[2]
0.298
[3]
0.082
[4]
-
[5]
-
[25] array · 6 items
[0]
[1]
IL10
[2]
0.291
[3]
0.089
[4]
-
[5]
-
[26] array · 6 items
[0]
M1 macrophages
[1]
NOS2
[2]
0.102
[3]
0.559
[4]
-
[5]
-
[27] array · 6 items
[0]
[1]
ROS
[2]
0.121
[3]
0.488
[4]
-
[5]
-
[28] array · 6 items
[0]
M2 macrophages
[1]
ARG1
[2]
0.124
[3]
0.477
[4]
-
[5]
-
[29] array · 6 items
[0]
[1]
MRC1
[2]
0.092
[3]
0.599
[4]
-
[5]
-
[30] array · 6 items
[0]
Monocyte
[1]
CD14
[2]
0.245
[3]
0.155
[4]
-
[5]
-
[31] array · 6 items
[0]
[1]
CD33
[2]
0.384
[3]
0.023
[4]
-
[5]
-
[32] array · 6 items
[0]
NK
[1]
XCL1
[2]
0.066
[3]
0.708
[4]
-
[5]
-
[33] array · 6 items
[0]
[1]
KIR3DL1
[2]
0.002
[3]
0.991
[4]
-
[5]
-
[34] array · 6 items
[0]
[1]
CD7
[2]
0.135
[3]
0.440
[4]
-
[5]
-
[35] array · 6 items
[0]
Neutrophil
[1]
MPO
[2]
0.074
[3]
0.671
[4]
-
[5]
-
[36] array · 6 items
[0]
Dendritic cell
[1]
CD80
[2]
0.602
[3]
<0.001
[4]
-
[5]
-
[37] array · 6 items
[0]
[1]
CD83
[2]
0.456
[3]
0.006
[4]
-
[5]
-
[38] array · 6 items
[0]
[1]
CD86
[2]
0.500
[3]
0.002
[4]
-
[5]
-
locator
section[9]/table-wrap[1]#t3
[5] object · 16 fields
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asset:table:pmid:33216732:4
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table
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jats-table
media_type
application/vnd.jats.table+json
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null
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sha256:174194cd8e4151fc2593d8f2db2f910426489ef6b274d3254369eb6003010605
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1446
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read_table
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identifier
section[9]/table-wrap[2]#t4
version
null
note
Correlations between OSM and genes markers of B cells, T helper cells, TAMs, monocytes, DCs and MDSCs in GEPIA by spearman analysis.
structure object · 5 fields
pmcid
PMC11623973
section_index
9
section_title
OSM expression correlates with tumor infiltration of immune cells in CCA tissues
row_count
27
column_count
6
table object · 8 fields
label
Table 4
caption
Correlations between OSM and genes markers of B cells, T helper cells, TAMs, monocytes, DCs and MDSCs in GEPIA by spearman analysis.
rows array · 27 items
[0] array · 4 items
[0]
Cell type
[1]
Gene marker
[2]
Tumor
[3]
Normal
[1] array · 6 items
[0]
[1]
[2]
Cor
[3]
P
[4]
Cor
[5]
P
[2] array · 6 items
[0]
B cell
[1]
CD19
[2]
0.22
[3]
0.2
[4]
-0.46
[5]
0.21
[3] array · 6 items
[0]
[1]
CD22
[2]
0.33
[3]
0.051
[4]
0.3
[5]
0.43
[4] array · 6 items
[0]
[1]
CD70
[2]
0.4
[3]
0.016
[4]
-0.17
[5]
0.66
[5] array · 6 items
[0]
Tfh
[1]
CXCR5
[2]
0.046
[3]
0.79
[4]
-0.17
[5]
0.68
[6] array · 6 items
[0]
[1]
ICOS
[2]
0.52
[3]
0.001
[4]
0.53
[5]
0.14
[7] array · 6 items
[0]
[1]
BCL-6
[2]
0.31
[3]
0.064
[4]
0.67
[5]
0.059
[8] array · 6 items
[0]
Thl
[1]
IL12RB2
[2]
0.3
[3]
0.072
[4]
0.35
[5]
0.35
[9] array · 6 items
[0]
[1]
T-bet (TBX21)
[2]
0.31
[3]
0.066
[4]
[5]
[10] array · 6 items
[0]
[1]
STAT4
[2]
0.2
[3]
0.24
[4]
0.05
[5]
0.91
[11] array · 6 items
[0]
Th2
[1]
CCR3
[2]
0.26
[3]
0.13
[4]
0.35
[5]
0.36
[12] array · 6 items
[0]
[1]
CCR4
[2]
0.46
[3]
0.005
[4]
0.37
[5]
0.34
[13] array · 6 items
[0]
Th17
[1]
IL-23R
[2]
0.42
[3]
0.012
[4]
-0.028
[5]
0.94
[14] array · 6 items
[0]
[1]
STAT3
[2]
0.19
[3]
0.25
[4]
0.57
[5]
0.12
[15] array · 6 items
[0]
Treg
[1]
FOXP3
[2]
0.41
[3]
0.012
[4]
-0.2
[5]
0.61
[16] array · 6 items
[0]
[1]
IL-2Ra
[2]
0.45
[3]
0.006
[4]
0.084
[5]
0.83
[17] array · 6 items
[0]
TAM
[1]
CCL2
[2]
0.14
[3]
0.42
[4]
0.65
[5]
0.06
[18] array · 6 items
[0]
[1]
CD68
[2]
0.21
[3]
0.22
[4]
0.23
[5]
0.54
[19] array · 6 items
[0]
[1]
IL10
[2]
0.28
[3]
0.095
[4]
0.71
[5]
0.034
[20] array · 6 items
[0]
Monocyte
[1]
CD14
[2]
0.43
[3]
0.009
[4]
0.43
[5]
0.25
[21] array · 6 items
[0]
[1]
CD33
[2]
0.46
[3]
0.005
[4]
-0.05
[5]
0.91
[22] array · 6 items
[0]
Dendritic cell
[1]
CD80
[2]
0.68
[3]
<0.001
[4]
0.47
[5]
0.2
[23] array · 6 items
[0]
[1]
CD83
[2]
0.55
[3]
<0.001
[4]
0.37
[5]
0.34
[24] array · 6 items
[0]
[1]
CD86
[2]
0.64
[3]
<0.001
[4]
0.63
[5]
0.076
[25] array · 6 items
[0]
MDSCs
[1]
CD33
[2]
0.46
[3]
0.005
[4]
-0.05
[5]
0.91
[26] array · 6 items
[0]
[1]
CD11b
[2]
0.22
[3]
0.2
[4]
0.53
[5]
0.15
locator
section[9]/table-wrap[2]#t4
[6] object · 16 fields
id
asset:table:pmid:33216732:5
role
table
format
jats-table
media_type
application/vnd.jats.table+json
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null
sha256
sha256:4739fb37b2d84be4fe7ae59e547dd582371e583e55fec6846004c84c055aa6e8
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372
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read_table
reader_status
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identifier
section[10]/table-wrap[1]#t5
version
null
note
OSM expression correlates with four immune regulatory checkpoints in CCA tissue.
structure object · 5 fields
pmcid
PMC11623973
section_index
10
section_title
OSM expression correlates with three immune regulatory checkpoints in CCA tissues
row_count
3
column_count
9
table object · 8 fields
label
Table 5
caption
OSM expression correlates with four immune regulatory checkpoints in CCA tissue.
rows array · 3 items
[0] array · 5 items
[0]
[1]
CTLA4
[2]
HAVCR2
[3]
LAG3
[4]
PDL1
[1] array · 8 items
[0]
Cor
[1]
P
[2]
Cor
[3]
P
[4]
Cor
[5]
P
[6]
Cor
[7]
P
[2] array · 9 items
[0]
OSM
[1]
0.33
[2]
0.049
[3]
0.45
[4]
0.006
[5]
0.13
[6]
0.45
[7]
0.43
[8]
0.009
locator
section[10]/table-wrap[1]#t5
[7] object · 16 fields
id
asset:table:pmid:33216732:6
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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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sha256:69011409380a657b33cee4faf04272f88e723988ae9b6fc501a6094633feda44
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2770
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read_table
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identifier
section[11]/table-wrap[1]#t6
version
null
note
Gene Set Enrichment Analysis (GSEA) reveals biological function of OSM in CCA.
structure object · 5 fields
pmcid
PMC11623973
section_index
11
section_title
Functional enrichment analysis of OSM-related genes in CCA tissues
row_count
43
column_count
4
table object · 8 fields
label
Table 6
caption
Gene Set Enrichment Analysis (GSEA) reveals biological function of OSM in CCA.
rows array · 43 items
[0] array · 4 items
[0]
GO/KEGG pathway Description
[1]
Gene Count
[2]
Enrichment Score
[3]
P Value
[1] array · 4 items
[0]
GO terms for biological process (BP)
[1]
[2]
[3]
[2] array · 4 items
[0]
Positive Regulation of Acute Inflammatory Response
[1]
28
[2]
0.69
[3]
<0.001
[3] array · 4 items
[0]
Innate Immune Response Activating Cell Surface Receptor Signaling Pathway
[1]
106
[2]
0.55
[3]
<0.001
[4] array · 4 items
[0]
Regulation of Neutrophil Migration
[1]
30
[2]
0.68
[3]
<0.001
[5] array · 4 items
[0]
Positive Regulation of Neutrophil Migration
[1]
26
[2]
0.68
[3]
<0.001
[6] array · 4 items
[0]
Inflammatory Response
[1]
440
[2]
0.54
[3]
<0.001
[7] array · 4 items
[0]
Cilium Movement
[1]
31
[2]
-0.62
[3]
0.021
[8] array · 4 items
[0]
Photoreceptor Cell Maintenance
[1]
34
[2]
-0.55
[3]
0.021
[9] array · 4 items
[0]
Regulation of Activin Receptor Signaling Pathway
[1]
25
[2]
-0.55
[3]
0.022
[10] array · 4 items
[0]
Protein Transport Along Microtubule
[1]
26
[2]
-0.57
[3]
0.039
[11] array · 4 items
[0]
Negative Regulation of Protein Kinase B Signaling
[1]
33
[2]
-0.47
[3]
0.04
[12] array · 4 items
[0]
GO terms for cellular component (CC)
[1]
[2]
[3]
[13] array · 4 items
[0]
Recycling Endosome Membrane
[1]
40
[2]
0.5
[3]
0.023
[14] array · 4 items
[0]
Extrinsic Component of Cytoplasmic Side of Plasma Membrane
[1]
97
[2]
0.55
[3]
<0.001
[15] array · 4 items
[0]
Cytoplasmic Side of Membrane
[1]
167
[2]
0.48
[3]
0.021
[16] array · 4 items
[0]
Immunological Synapse
[1]
31
[2]
0.65
[3]
0.038
[17] array · 4 items
[0]
Extrinsic Component of Membrane
[1]
245
[2]
0.46
[3]
0.047
[18] array · 4 items
[0]
Ciliary Tip
[1]
42
[2]
-0.61
[3]
0.017
[19] array · 4 items
[0]
Mitochondrial Membrane Part
[1]
140
[2]
-0.58
[3]
0.023
[20] array · 4 items
[0]
Mitochondrial Protein Complex
[1]
108
[2]
-0.62
[3]
0.023
[21] array · 4 items
[0]
Organelle Inner Membrane
[1]
472
[2]
-0.48
[3]
<0.001
[22] array · 4 items
[0]
Intrinsic Component of Mitochondrial Inner Membrane
[1]
16
[2]
-0.63
[3]
0.043
[23] array · 4 items
[0]
GO terms for molecular function (MF)
[1]
[2]
[3]
[24] array · 4 items
[0]
Immunoglobulin Binding
[1]
21
[2]
0.76
[3]
<0.001
[25] array · 4 items
[0]
Tumor Necrosis Factor Receptor Binding
[1]
29
[2]
0.65
[3]
<0.001
[26] array · 4 items
[0]
Chemokine Activity
[1]
46
[2]
0.6
[3]
0.023
[27] array · 4 items
[0]
Cytokine Receptor Binding
[1]
264
[2]
0.44
[3]
<0.001
[28] array · 4 items
[0]
Cytokine Receptor Activity
[1]
85
[2]
0.56
[3]
0.059
[29] array · 4 items
[0]
Oxidoreductase Activity Acting on NAD P H Quinone Or Similar Compound as Acceptor
[1]
52
[2]
-0.67
[3]
0.021
[30] array · 4 items
[0]
Oxidoreductase Activity Acting on A Heme Group of Donors
[1]
25
[2]
-0.64
[3]
0.021
[31] array · 4 items
[0]
Oxidoreductase Activity Acting on NAD P H
[1]
92
[2]
-0.51
[3]
0.042
[32] array · 4 items
[0]
Gaba Receptor Activity
[1]
22
[2]
-0.58
[3]
0.039
[33] array · 4 items
[0]
Metal Cluster Binding
[1]
61
[2]
-0.46
[3]
0.04
[34] array · 4 items
[0]
KEGG signaling pathways
[1]
[2]
[3]
[35] array · 4 items
[0]
JAK Stat Signaling Pathway
[1]
151
[2]
0.52
[3]
<0.001
[36] array · 4 items
[0]
Toll Like Receptor Signaling Pathway
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Kaplan-Meier survival curve analysis and log-rank test showed that overall survival was significantly shorter for CCA patients with low OSM expression (OSMlow group) compared to those in the OSMhighgroup (Figure 5D).
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udy, we used bioinformatics tools to analyze transcriptome data from cholangiocarcinoma (CCA) patients
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CGA and ICGC databases for further analysis. RNA-seq data processing We used the R software packa
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ndent predictor of prognosis in CCA patients Western blot assays in 12 paired CCA tumor and adjacent n
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clinicopathological characteristics and OSM immunohistochemistry. We also recruited 5 out of 208 patients bet
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Sen university cohort of 203 CCA patients by IHC and divided the patients into high- and low-
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Kaplan-Meier survival curve analysis and log-rank test showed that overall survival was significantly shorter for CCA patients with low OSM expression (OSMlow group) compared to those in the OSMhighgroup (Figure 5D).
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Complete file
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We identified 96 differentially expressed genes (DEGs), including 13 upregulated and 83 downregulated genes, in CCA tissues as regulatory T cells were significantly higher and the proportions of activated natural killer cells and monocytes were significantly lower in CCA tissues than the precancerous tissues. The survival outcomes of CCA patients were associated with the TP53 gene mutation status, levels of Oncostatin M (OSM) expression, and the proportions of tumor-infiltrating immune cell types, including dendritic cells, monocytes, and T follicular helper cells. Functional enrichment analysis of the DEGs in the high OSM-expressing CCA tissues showed that pathways related to tumor progression and immune response were significantly upregulated. Our study demonstrates that OSM expression and TP53 mutation status regulate the tumor infiltration by immune cells and survival outcomes in CCA. 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["Mitochondrial Membrane Part", "140", "-0.58", "0.023"], ["Mitochondrial Protein Complex", "108", "-0.62", "0.023"], ["Organelle Inner Membrane", "472", "-0.48", "<0.001"], ["Intrinsic Component of Mitochondrial Inner Membrane", "16", "-0.63", "0.043"], ["GO terms for molecular function (MF)", "", "", ""], ["Immunoglobulin Binding", "21", "0.76", "<0.001"], ["Tumor Necrosis Factor Receptor Binding", "29", "0.65", "<0.001"], ["Chemokine Activity", "46", "0.6", "0.023"], ["Cytokine Receptor Binding", "264", "0.44", "<0.001"], ["Cytokine Receptor Activity", "85", "0.56", "0.059"], ["Oxidoreductase Activity Acting on NAD P H Quinone Or Similar Compound as Acceptor", "52", "-0.67", "0.021"], ["Oxidoreductase Activity Acting on A Heme Group of Donors", "25", "-0.64", "0.021"], ["Oxidoreductase Activity Acting on NAD P H", "92", "-0.51", "0.042"], ["Gaba Receptor Activity", "22", "-0.58", "0.039"], ["Metal Cluster Binding", "61", "-0.46", "0.04"], ["KEGG signaling pathways", "", "", ""], 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["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Kaplan-Meier survival curve analysis and log-rank test showed that overall survival was significantly shorter for CCA patients with low OSM expression (OSMlow group) compared to those in the OSMhighgroup (Figure 5D)."}}, {"id": "method-2", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {"hazard_ratio": "wed that tumor numbers (HR=1"}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "Cox regression"}}, {"id": "method-3", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", 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This study was approved by the Ethics Commi"], "order_basis": "paper_text_order:4655", "id": "assay:2"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["clinicopathological characteristics and OSM immunohistochemistry. We also recruited 5 out of 208 patients bet", "(P) by western blotting. (B) Representative immunostaining images of OSM in CCA. (C) Boxplots depicted", "Sen university cohort of 203 CCA patients by IHC and divided the patients into high- and low-", "=101 and n=102, respectively) using a median IHC expression score of 4 (Figure 6B). Kaplan-Me"], "order_basis": "paper_text_order:5061", "id": "assay:3"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Kaplan-Meier survival curve analysis and log-rank test showed that overall survival was significantly shorter for CCA patients with low OSM expression (OSMlow group) compared to those in the OSMhighgroup (Figure 5D)."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}