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Lu et al. Hepatoma Research 2018;4:21 Hepatoma Research
DOI: 10.20517/2394-5079.2018.44

Review Open Access

Pathway analysis provides insight into the genetic
susceptibility to hepatocellular carcinoma and
insight into immuno-therapy treatment response

1
1
Yih-Kuang Lu , Jacob Morris Brill , Ardesher Aghili , Kenneth Howard Buetow 1,2,3
1
1 Computational Sciences and Informatics, Complex Adaptive Systems, Arizona State University, Tempe, AZ 85287, USA.
2 Center for Evolution and Medicine, Arizona State University, Tempe, AZ 85287, USA.
3 School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA.
Correspondence to: Dr. Kenneth Howard Buetow, Computational Sciences and Informatics, Complex Adaptive Systems, Arizona State
University, Tempe, AZ 85287, USA. E-mail: kenneth.buetow@asu.edu

How to cite this article: Lu YK, Brill JM, Aghili A, Buetow KH. Pathway analysis provides insight into the genetic susceptibility to
hepatocellular carcinoma and insight into immuno-therapy treatment response. Hepatoma Res 2018;4:21.
http://dx.doi.org/10.20517/2394-5079.2018.44
Received: 26 Apr 2018 First Decision: 28 May 2018 Revised: 11 Jun 2018 Accepted: 12 Jun 2018 Published: 22 Jun 2018

Science Editor: Guang-Wen Cao Copy Editor: Jun-Yao Li Production Editor: Huan-Liang Wu

Abstract
Clear evidence exists for genetic susceptibility to hepatocellular carcinoma (HCC). Genome-wide association
studies have identified multiple candidate susceptibility loci. These loci suggest that genetic variation in the
immune system may underpin HCC susceptibility. Genes for the antigen processing and presentation pathway
have been observed to be significantly enriched across studies and the pathway is identified directly through
genome-wide studies of variation using pathway methods. Detailed analysis of the pathway indicates both
variation in the antigen presenting loci and in the antigen processing are different in cases in controls. Pathway
analysis at the transcriptional level also shows difference between normal liver and liver in individuals with
HCC. Assessing differences in the pathway may prove important in improving immune therapy for HCC and in
identifying responders for immune checkpoint therapy.

Keywords: Hepatocellular carcinoma, genetic susceptibility, genome-wide association study, pathway analysis,
antigen presentation and processing, immune checkpoint therapy

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is ranked 5th in global
[1]
incidence and 2nd in mortality . With the exception of East Asia, the incidence of HCC is increasing
[2]
in almost all regions of the world and has doubled in the USA since the early 1980s . This increase is
[3,4]
attributable to increases in obesity and type II diabetes . Liver cancer’s 5-year survival is the second worst
[5]
among all cancers (18.1%) .
© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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