CXCL1 and CXCL6 Are Potential Predictors for HCC Response to TACE

Curr Oncol. 2023 Mar 20;30(3):3516-3528. doi: 10.3390/curroncol30030267.

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.

Keywords: biomarker; hepatocellular carcinoma; immune profiling; transarterial chemoembolization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / therapy
  • Chemoembolization, Therapeutic*
  • Chemokine CXCL1 / genetics
  • Chemokine CXCL6
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / therapy
  • Prognosis
  • Retrospective Studies

Substances

  • Chemokine CXCL1
  • Chemokine CXCL6
  • CXCL1 protein, human
  • CXCL6 protein, human

Grants and funding

M.N.K. and A.S. were supported by a rotation grant for medical scientists in the Frankfurt Research Promotion Program (FFF) of the Faculty of Medicine of the Goethe University. S.B. and this work were supported in part by the Trusts of the Faculty of Medicine of the Goethe University (“Stiftungen und Vereine–Stiftungsmittel des Fachbereichs”). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; prepartion, review, or approval of the manuscript; and decision to submit the manuscript for publication.