PMID- 35773268
OWN - NLM
STAT- MEDLINE
DCOM- 20220704
LR  - 20240102
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Jun 30
TI  - Deeper insights into long-term survival heterogeneity of pancreatic ductal 
      adenocarcinoma (PDAC) patients using integrative individual- and group-level 
      transcriptome network analyses.
PG  - 11027
LID - 10.1038/s41598-022-14592-1 [doi]
LID - 11027
AB  - Pancreatic ductal adenocarcinoma (PDAC) is categorized as the leading cause of 
      cancer mortality worldwide. However, its predictive markers for long-term 
      survival are not well known. It is interesting to delineate individual-specific 
      perturbed genes when comparing long-term (LT) and short-term (ST) PDAC survivors 
      and integrate individual- and group-based transcriptome profiling. Using a 
      discovery cohort of 19 PDAC patients from CHU-Liege (Belgium), we first performed 
      differential gene expression analysis comparing LT to ST survivor. Second, we 
      adopted systems biology approaches to obtain clinically relevant gene modules. 
      Third, we created individual-specific perturbation profiles. Furthermore, we used 
      Degree-Aware disease gene prioritizing (DADA) method to develop PDAC disease 
      modules; Network-based Integration of Multi-omics Data (NetICS) to integrate 
      group-based and individual-specific perturbed genes in relation to PDAC LT 
      survival. We identified 173 differentially expressed genes (DEGs) in ST and LT 
      survivors and five modules (including 38 DEGs) showing associations to clinical 
      traits. Validation of DEGs in the molecular lab suggested a role of REG4 and 
      TSPAN8 in PDAC survival. Via NetICS and DADA, we identified various known 
      oncogenes such as CUL1 and TGFB1. Our proposed analytic workflow shows the 
      advantages of combining clinical and omics data as well as individual- and 
      group-level transcriptome profiling.
CI  - (c) 2022. The Author(s).
FAU - Bhardwaj, Archana
AU  - Bhardwaj A
AD  - GIGA-R Centre, BIO3 - Medical Genomics, University of Liege, Avenue de L'Hopital, 
      11, 4000, Liege, Belgium. a.bhardwaj@uliege.be.
FAU - Josse, Claire
AU  - Josse C
AD  - Laboratory of Human Genetics, GIGA Research, University Hospital (CHU), Liege, 
      Belgium.
AD  - Medical Oncology Department, CHU Liege, Liege, Belgium.
FAU - Van Daele, Daniel
AU  - Van Daele D
AD  - Department of Gastro-Enterology, University Hospital (CHU), Liege, Belgium.
FAU - Poulet, Christophe
AU  - Poulet C
AD  - Laboratory of Human Genetics, GIGA Research, University Hospital (CHU), Liege, 
      Belgium.
AD  - Laboratory of Rheumatology, GIGA-R, University Hospital (CHULiege), Liege, 
      Belgium.
FAU - Chavez, Marcela
AU  - Chavez M
AD  - Department of Medicine, Division of Hematology, University Hospital (CHU), Liege, 
      Belgium.
FAU - Struman, Ingrid
AU  - Struman I
AD  - GIGA-R Centre, Laboratory of Molecular Angiogenesis, University of Liege, Liege, 
      Belgium.
FAU - Van Steen, Kristel
AU  - Van Steen K
AD  - GIGA-R Centre, BIO3 - Medical Genomics, University of Liege, Avenue de L'Hopital, 
      11, 4000, Liege, Belgium.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220630
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (TSPAN8 protein, human)
RN  - 0 (Tetraspanins)
SB  - IM
MH  - Biomarkers, Tumor/genetics
MH  - *Carcinoma, Pancreatic Ductal/pathology
MH  - Gene Expression Profiling/methods
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - *Pancreatic Neoplasms/pathology
MH  - Tetraspanins/metabolism
MH  - Transcriptome
PMC - PMC9247075
COIS- The authors declare no competing interests.
EDAT- 2022/07/01 06:00
MHDA- 2022/07/06 06:00
PMCR- 2022/06/30
CRDT- 2022/06/30 23:16
PHST- 2021/07/09 00:00 [received]
PHST- 2022/06/09 00:00 [accepted]
PHST- 2022/06/30 23:16 [entrez]
PHST- 2022/07/01 06:00 [pubmed]
PHST- 2022/07/06 06:00 [medline]
PHST- 2022/06/30 00:00 [pmc-release]
AID - 10.1038/s41598-022-14592-1 [pii]
AID - 14592 [pii]
AID - 10.1038/s41598-022-14592-1 [doi]
PST - epublish
SO  - Sci Rep. 2022 Jun 30;12(1):11027. doi: 10.1038/s41598-022-14592-1.