Z Gastroenterol 2020; 58(01): e43
DOI: 10.1055/s-0039-3402216
Poster Visit Session IV Tumors: Saturday, February 15, 2020, 8:30 am – 09:15 am, Lecture Hall P1
Georg Thieme Verlag KG Stuttgart · New York

HILPDA is upregulated, predicts prognosis and promotes cancer progression in hepatocellular carcinoma

D Ridder
1   University Medical Center of the Johannes Gutenberg University, Institute of Pathology, Mainz, Germany
,
K Berndt
1   University Medical Center of the Johannes Gutenberg University, Institute of Pathology, Mainz, Germany
,
HR Witzel
1   University Medical Center of the Johannes Gutenberg University, Institute of Pathology, Mainz, Germany
,
A Weinmann
2   University Medical Center of the Johannes Gutenberg University, Department of Internal Medicine, Mainz, Germany
,
JU Marquardt
2   University Medical Center of the Johannes Gutenberg University, Department of Internal Medicine, Mainz, Germany
,
M Schindeldecker
1   University Medical Center of the Johannes Gutenberg University, Institute of Pathology, Mainz, Germany
3   University Medical Center of the Johannes Gutenberg University, Tissue Bank, Mainz, Germany
,
S Heinrich
4   University Medical Center of the Johannes Gutenberg University, Department of General-, Visceral- and Transplant Surgery, Mainz, Germany
,
W Roth
1   University Medical Center of the Johannes Gutenberg University, Institute of Pathology, Mainz, Germany
,
B Straub
1   University Medical Center of the Johannes Gutenberg University, Institute of Pathology, Mainz, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
03 January 2020 (online)

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Aim:

Liver cancer is the second most common cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) being its predominant form. There is an urgent need to identify new prognostic markers to determine prognosis and select specific therapies. Hypoxia-inducible lipid droplet-associated protein (HILPDA) is induced in different cancer types, predicts worse prognosis and inhibits fatty acid oxidation, but its role in HCC, a tumor that frequently shows increased amounts of lipid droplets, has not been investigated so far.

Methods:

In order to investigate HILPDA-expression in HCCs in a large cohort of patients by immunohistochemistry, we established an HCC tissue microarray of 574 patients. Kaplan-Meier, Wilcoxon rank-sum test, log rank and univariate Cox's regression analysis and Spearman's rank correlation were used to determine associations between HILPDA-expression, patient survival, etiology of underlying liver disease and other clinical parameters. In vitro, proliferation rate and migratory activity were analyzed in Huh7 cells upon HILPDA overexpression.

Results:

We detected specific HILPDA immunoreactivity in over 95% of the HCCs, with strong HILPDA expression in about 5%, intermediate expression in about 25% and low expression in about 65% of primary HCCs. HILPDA was significantly induced in HCCs compared to surrounding non-neoplastic normal and cirrhotic liver tissue, and even further increased in lymph node metastases and recurrent HCCs. Increased HILPDA expression correlated with decreased survival (HR 1.31; 95% CI, 1.04 – 1.64, p < 0.05) and was associated with higher tumor grade, increased proliferation, and micro- and macrovascular invasion. Patients suffering from chronic hepatitis C showed increased HILPDA levels in HCC and non-neoplastic liver, whereas hemochromatosis and NASH were associated with lower HILPDA expression. We did not detect a significant association of HILPDA expression with other clinical parameters. In vitro, HILPDA overexpression resulted in an increased proliferation rate and increased tumor cell migration.

Conclusion:

HILPDA expression was induced in HCC and was further increased in relapses and lymph node metastases, as determined by immunohistochemistry. Higher HILPDA levels were associated with unfavorable prognosis, higher tumor grade and micro- and macrovascular invasion. Mechanistically, HILPDA overexpression led to increased tumor cell proliferation and increased migratory activity.