PMID- 32010606
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 9
DP  - 2019
TI  - Genomic Features and Clinical Characteristics of Adolescents and Young Adults 
      With Cholangiocarcinoma.
PG  - 1439
LID - 10.3389/fonc.2019.01439 [doi]
LID - 1439
AB  - Background: Adolescents and young adults (AYAs) diagnosed with cancer between 
      ages 15 and 45 years may exhibit unique biologic and genomic characteristics as 
      well as clinical features, resulting in differences in clinical characters and 
      drug resistance. However, compared to other solid cancers, relatively few studies 
      have been conducted in this age group in cholangiocarcinoma (CCA). This study is 
      performed to investigate the clinical and molecular features of AYAs with CCA. 
      Methods: Three cohorts, including the external dataset (TCGA and MSKCC) and the 
      perihilar CCA databank of Chinese tertiary hospitals, were contained in this 
      study. Pathway and process enrichment analysis had been carried out with the 
      following ontology sources: KEGG Pathway, GO Biological Processes, Reactome Gene 
      Sets, Canonical Pathways, and CORUM. Metascape and GEPIA datasets were used for 
      bioinformatic analysis. P < 0.05 was considered statistically significant. All 
      statistical analyses were performed with GraphPad Prism (version 7.0; GraphPad 
      Software, La Jolla, California) and R studio (version 3.6.1; R studio, Boston, 
      Massachusetts). Results: Compared to older adults, AYAs with CCA presented with 
      worse overall survival, although the difference was not significant. Specific to 
      patients with stage IV CCAs who underwent chemotherapy, AYAs were associated with 
      significantly poorer overall survival (OS) (p = 0.03, hazards ratio (HR) 3.01, 
      95% confidence interval (CI) 1.14-4.91). From the anatomical perspective, more 
      extrahepatic CCA was detected in the AYA group. Microsatellite instability (MSI) 
      occurred in 3% of older patients in the present study. Nevertheless, none of the 
      AYAs had MSI status. In this study, AYAs gained an enhanced frequency of 
      additional sex combs like 1 (ASXL1) (p = 0.02) and KMT2C (p = 0.02) mutation than 
      their older counterparts. Besides ASXL1 and KMT2C, the genes enriched in AYAs 
      with CCA were analyzed by pathway and process enrichment analysis. And those 
      genes were found to be associated with poorer differentiation, deubiquitination, 
      and WNT signal pathway. Moreover, AYAs were relevant to poor differentiation and 
      advanced tumor stage. Conclusion: This study offered a preliminary landscape of 
      the clinical and molecular features of early-onset biliary cancers. Further 
      studies including more samples are essential to investigate whether ASXL1 and 
      KMT2C could be considered as potentially targetable genomic signatures for young 
      patients.
CI  - Copyright (c) 2020 Feng, Tong, Yan, He, Chen and Wang.
FAU - Feng, Hao
AU  - Feng H
AD  - Department of Biliary-Pancreatic Surgery, School of Medicine, Renji Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
AD  - University Hospital of LMU Munich, Medical Faculty of 
      Ludwig-Maximilians-University of Munich, Munich, Germany.
FAU - Tong, Huan
AU  - Tong H
AD  - Clinical and Translational Research Center, Shanghai First Maternity and Infant 
      Hospital, Tongji University School of Medicine, Shanghai, China.
FAU - Yan, Jiayan
AU  - Yan J
AD  - Department of Biliary-Pancreatic Surgery, School of Medicine, Renji Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - He, Min
AU  - He M
AD  - Department of Biliary-Pancreatic Surgery, School of Medicine, Renji Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Biliary-Pancreatic Surgery, School of Medicine, Renji Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
FAU - Wang, Jian
AU  - Wang J
AD  - Department of Biliary-Pancreatic Surgery, School of Medicine, Renji Hospital, 
      Shanghai Jiao Tong University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20200114
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC6971196
OTO - NOTNLM
OT  - ASXL1
OT  - adolescents and young adults (AYAs)
OT  - cholangiocarcinoma
OT  - early-onset
OT  - mutation
EDAT- 2020/02/06 06:00
MHDA- 2020/02/06 06:01
PMCR- 2019/01/01
CRDT- 2020/02/04 06:00
PHST- 2019/08/06 00:00 [received]
PHST- 2019/12/03 00:00 [accepted]
PHST- 2020/02/04 06:00 [entrez]
PHST- 2020/02/06 06:00 [pubmed]
PHST- 2020/02/06 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2019.01439 [doi]
PST - epublish
SO  - Front Oncol. 2020 Jan 14;9:1439. doi: 10.3389/fonc.2019.01439. eCollection 2019.