CXCL1 and CXCL6 Are Potential Predictors for HCC Response to TACE

Author:

Kinzler Maximilian N.1ORCID,Bankov Katrin2ORCID,Bein Julia2,Döring Claudia2,Schulze Falko2,Reis Henning2ORCID,Mahmoudi Scherwin3,Koch Vitali3,Grünewald Leon D.3,Stehle Angelika1,Walter Dirk1,Finkelmeier Fabian1ORCID,Zeuzem Stefan1,Wild Peter J.245,Vogl Thomas J.3,Bernatz Simon2346ORCID

Affiliation:

1. Department of Internal Medicine I, University Hospital Frankfurt, Goethe University-Frankfurt am Main, 60590 Frankfurt am Main, Germany

2. Dr. Senckenberg Institute for Pathology, University Hospital Frankfurt, Goethe University Frankfurt am Main, 60590 Frankfurt am Main, Germany

3. Department of Diagnostic and Interventional Radiology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany

4. Frankfurt Cancer Institute (FCI), Goethe University, 60590 Frankfurt am Main, Germany

5. Frankfurt Institute for Advanced Studies (FIAS), 60438 Frankfurt am Main, Germany

6. University Cancer Center Frankfurt (UCT), University Hospital, Goethe University, 60590 Frankfurt am Main, Germany

Abstract

Distinct immune patterns of hepatocellular carcinoma (HCC) may have prognostic implications in the response to transarterial chemoembolization (TACE). Thus, we aimed to exploratively analyze tumor tissue of HCC patients who do or do not respond to TACE, and to identify novel prognostic biomarkers predictive of response to TACE. We retrospectively included 15 HCC patients who had three consecutive TACE between January 2019 and November 2019. Eight patients had a response while seven patients had no response to TACE. All patients had measurable disease according to mRECIST. Corresponding tumor tissue samples were processed for differential expression profiling using NanoString nCounter® PanCancer immune profiling panel. Immune-related pathways were broadly upregulated in TACE responders. The top differentially regulated genes were the upregulated CXCL1 (log2fc 4.98, Benjamini–Hochberg (BH)-p < 0.001), CXCL6 (log2fc 4.43, BH-p = 0.016) and the downregulated MME (log2fc −4.33, BH-p 0.001). CD8/T-regs was highly increased in responders, whereas the relative number of T-regs to tumor-infiltrating lymphocytes (TIL) was highly decreased. We preliminary identified CXCL1 and CXCL6 as candidate genes that might have the potential to serve as therapeutically relevant biomarkers in HCC patients. This might pave the way to improve patient selection for TACE in HCC patients beyond expert consensus.

Funder

Frankfurt Research Promotion Program

Trusts of the Faculty of Medicine of the Goethe University

Publisher

MDPI AG

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