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Poster Display session 2

3180 - Genomic analysis of hepatobiliary lithiasis associated cholangiocarcinoma revealed a distinct subtype feature.

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Hepatobiliary Cancers

Presenters

Lunda Gu

Citation

Annals of Oncology (2019) 30 (suppl_5): v253-v324. 10.1093/annonc/mdz247

Authors

L. Gu1, Y. Wang2, J. Deng1, X. Chen1, J. Zhou2, X. Yang2

Author affiliations

  • 1 Research Institute, BGI-Shenzhen, 518083 - Shenzhen/CN
  • 2 Liver Surgery, Zhongshan Hospital, Fudan University, 200032 - Shanghai/CN

Resources

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Abstract 3180

Background

Hepatic stone or lithiasis is a known risk factor for intrahepatic cholangiocarcinoma (ICC) in clinic, however the process and genomic background of the hepatobiliary lithiasis associated cholangiocarcinoma (BCAC) is completely unknown.

Methods

Here, we retrospectively collected 81 paired intrahepatic cholangiocarcinoma (ICC) frozen cancerous and adjacent tissues including those patients combining biliary calculi. Whole exome sequence (WES, average 400x) and RNA-seq were applied to characterize this cohort.

Results

Among them, prognosis of 64 patients from 2011 to 2013 revealed that BCAC had poor overall survival (18.6 months vs 28.6 months, P = 0.024, Kaplan-Meier) compared to those of non-stone ICC. WES of 81 ICC patients showed that BCAC displayed a distinct mutation pattern, with EPHA2 and SMAD4 genes significantly enriched in BCAC (P < 0.05, Fisher exact test) and epigenetic regulators IDH1, BAP1 and calcium channel RYR1 more enriched in non-calculi ICCs. Transcriptome profile showed that BCAC was different from canonical ICCs. Gene set enrichment analysis revealed that RESPONSE_TO_LIPID and CALCIUM_ION_BINDING were among the top significant changed gene sets, which might play important roles in BCACs.

Conclusions

Our results demonstrate that BCAC is a distinct CCAs subtype and biliary calculi might be an independent factor for ICC and result in a poor prognosis.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

BGI-Shenzhen.

Funding

Shenzhen Science and Technology Innovation Committee.

Disclosure

All authors have declared no conflicts of interest.

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