Circulating levels of PD-L1 and Galectin-9 are associated with patient survival in surgically treated Hepatocellular Carcinoma independent of their intra-tumoral expression levels

Kostandinos Sideras, Robert A. de Man, Susan M. Harrington, Wojciech G. Polak, Guoying Zhou, Hannah M. Schutz, Alexander Pedroza-Gonzalez, Katharina Biermann, Shanta Mancham, Bettina E. Hansen, R. Bart Takkenberg, Anneke J. van Vuuren, Qiuwei Pan, Jan N.M. Ijzermans, Stefan Sleijfer, Dave Sprengers, Haidong M Dong, Jaap Kwekkeboom, Marco J. Bruno

Research output: Contribution to journalArticle

Abstract

Tumor expression of immune co-inhibitory ligands, such as PD-L1 and Galectin-9, have potential prognostic value in Hepatocellular Carcinoma (HCC). Circulating levels of these molecules, however, have hardly been studied. This study aims to assess the prognostic significance of circulating PD-L1 and circulating Galectin-9 in patients with resected HCC, and to compare their prognostic significance to the intra-tumoral expression of these same molecules. Archived tissues and stored peripheral blood samples from 81 patients who underwent HCC resection or liver transplantation, with curative intent, were used. Immunohistochemistry was performed to determine intra-tumoral expression of PD-L1 and Galectin-9, while ELISA was used to quantify their respective circulating levels. High circulating PD-L1 (HR 0.12, 95%CI 0.16–0.86, p = 0.011) and high circulating Galectin-9 (HR 0.11, 95%CI 0.15–0.85, p = 0.010) levels were both associated with improved HCC-specific survival. Surprisingly, there was no correlation between circulating levels of PD-L1 and Galectin-9 and their intra-tumoral expression levels. In fact, circulating levels of PD-L1 and Galectin-9 were predictive of HCC-specific survival independently of intra-tumoral levels and baseline clinicopathologic characteristics. Combined analysis of circulating levels and intra-tumoral expression of PD-L1 (HR 0.33, 95%CI 0.16–0.68, p = 0.002) and Galectin-9 (HR 0.27, 95%CI 0.13–0.57, p = 0.001) resulted in more confident prediction of survival. In conclusion, circulating PD-L1 and Galectin-9 levels prognostically differentiate resected HCC patients, independently of their intra-tumoral expression. Combining circulating and intra-tumoral expression levels of PD-L1 or Galectin-9 further improves the prognostic values of these immune biomarkers.

Original languageEnglish (US)
Article number10677
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

Fingerprint

Galectins
Hepatocellular Carcinoma
Survival
Liver Transplantation
Biomarkers
Enzyme-Linked Immunosorbent Assay
Immunohistochemistry
Ligands

ASJC Scopus subject areas

  • General

Cite this

Circulating levels of PD-L1 and Galectin-9 are associated with patient survival in surgically treated Hepatocellular Carcinoma independent of their intra-tumoral expression levels. / Sideras, Kostandinos; de Man, Robert A.; Harrington, Susan M.; Polak, Wojciech G.; Zhou, Guoying; Schutz, Hannah M.; Pedroza-Gonzalez, Alexander; Biermann, Katharina; Mancham, Shanta; Hansen, Bettina E.; Bart Takkenberg, R.; van Vuuren, Anneke J.; Pan, Qiuwei; Ijzermans, Jan N.M.; Sleijfer, Stefan; Sprengers, Dave; Dong, Haidong M; Kwekkeboom, Jaap; Bruno, Marco J.

In: Scientific reports, Vol. 9, No. 1, 10677, 01.12.2019.

Research output: Contribution to journalArticle

Sideras, K, de Man, RA, Harrington, SM, Polak, WG, Zhou, G, Schutz, HM, Pedroza-Gonzalez, A, Biermann, K, Mancham, S, Hansen, BE, Bart Takkenberg, R, van Vuuren, AJ, Pan, Q, Ijzermans, JNM, Sleijfer, S, Sprengers, D, Dong, HM, Kwekkeboom, J & Bruno, MJ 2019, 'Circulating levels of PD-L1 and Galectin-9 are associated with patient survival in surgically treated Hepatocellular Carcinoma independent of their intra-tumoral expression levels', Scientific reports, vol. 9, no. 1, 10677. https://doi.org/10.1038/s41598-019-47235-z
Sideras, Kostandinos ; de Man, Robert A. ; Harrington, Susan M. ; Polak, Wojciech G. ; Zhou, Guoying ; Schutz, Hannah M. ; Pedroza-Gonzalez, Alexander ; Biermann, Katharina ; Mancham, Shanta ; Hansen, Bettina E. ; Bart Takkenberg, R. ; van Vuuren, Anneke J. ; Pan, Qiuwei ; Ijzermans, Jan N.M. ; Sleijfer, Stefan ; Sprengers, Dave ; Dong, Haidong M ; Kwekkeboom, Jaap ; Bruno, Marco J. / Circulating levels of PD-L1 and Galectin-9 are associated with patient survival in surgically treated Hepatocellular Carcinoma independent of their intra-tumoral expression levels. In: Scientific reports. 2019 ; Vol. 9, No. 1.
@article{7a94ac94f9f34eb7a8ac354702becb2d,
title = "Circulating levels of PD-L1 and Galectin-9 are associated with patient survival in surgically treated Hepatocellular Carcinoma independent of their intra-tumoral expression levels",
abstract = "Tumor expression of immune co-inhibitory ligands, such as PD-L1 and Galectin-9, have potential prognostic value in Hepatocellular Carcinoma (HCC). Circulating levels of these molecules, however, have hardly been studied. This study aims to assess the prognostic significance of circulating PD-L1 and circulating Galectin-9 in patients with resected HCC, and to compare their prognostic significance to the intra-tumoral expression of these same molecules. Archived tissues and stored peripheral blood samples from 81 patients who underwent HCC resection or liver transplantation, with curative intent, were used. Immunohistochemistry was performed to determine intra-tumoral expression of PD-L1 and Galectin-9, while ELISA was used to quantify their respective circulating levels. High circulating PD-L1 (HR 0.12, 95{\%}CI 0.16–0.86, p = 0.011) and high circulating Galectin-9 (HR 0.11, 95{\%}CI 0.15–0.85, p = 0.010) levels were both associated with improved HCC-specific survival. Surprisingly, there was no correlation between circulating levels of PD-L1 and Galectin-9 and their intra-tumoral expression levels. In fact, circulating levels of PD-L1 and Galectin-9 were predictive of HCC-specific survival independently of intra-tumoral levels and baseline clinicopathologic characteristics. Combined analysis of circulating levels and intra-tumoral expression of PD-L1 (HR 0.33, 95{\%}CI 0.16–0.68, p = 0.002) and Galectin-9 (HR 0.27, 95{\%}CI 0.13–0.57, p = 0.001) resulted in more confident prediction of survival. In conclusion, circulating PD-L1 and Galectin-9 levels prognostically differentiate resected HCC patients, independently of their intra-tumoral expression. Combining circulating and intra-tumoral expression levels of PD-L1 or Galectin-9 further improves the prognostic values of these immune biomarkers.",
author = "Kostandinos Sideras and {de Man}, {Robert A.} and Harrington, {Susan M.} and Polak, {Wojciech G.} and Guoying Zhou and Schutz, {Hannah M.} and Alexander Pedroza-Gonzalez and Katharina Biermann and Shanta Mancham and Hansen, {Bettina E.} and {Bart Takkenberg}, R. and {van Vuuren}, {Anneke J.} and Qiuwei Pan and Ijzermans, {Jan N.M.} and Stefan Sleijfer and Dave Sprengers and Dong, {Haidong M} and Jaap Kwekkeboom and Bruno, {Marco J.}",
year = "2019",
month = "12",
day = "1",
doi = "10.1038/s41598-019-47235-z",
language = "English (US)",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Circulating levels of PD-L1 and Galectin-9 are associated with patient survival in surgically treated Hepatocellular Carcinoma independent of their intra-tumoral expression levels

AU - Sideras, Kostandinos

AU - de Man, Robert A.

AU - Harrington, Susan M.

AU - Polak, Wojciech G.

AU - Zhou, Guoying

AU - Schutz, Hannah M.

AU - Pedroza-Gonzalez, Alexander

AU - Biermann, Katharina

AU - Mancham, Shanta

AU - Hansen, Bettina E.

AU - Bart Takkenberg, R.

AU - van Vuuren, Anneke J.

AU - Pan, Qiuwei

AU - Ijzermans, Jan N.M.

AU - Sleijfer, Stefan

AU - Sprengers, Dave

AU - Dong, Haidong M

AU - Kwekkeboom, Jaap

AU - Bruno, Marco J.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Tumor expression of immune co-inhibitory ligands, such as PD-L1 and Galectin-9, have potential prognostic value in Hepatocellular Carcinoma (HCC). Circulating levels of these molecules, however, have hardly been studied. This study aims to assess the prognostic significance of circulating PD-L1 and circulating Galectin-9 in patients with resected HCC, and to compare their prognostic significance to the intra-tumoral expression of these same molecules. Archived tissues and stored peripheral blood samples from 81 patients who underwent HCC resection or liver transplantation, with curative intent, were used. Immunohistochemistry was performed to determine intra-tumoral expression of PD-L1 and Galectin-9, while ELISA was used to quantify their respective circulating levels. High circulating PD-L1 (HR 0.12, 95%CI 0.16–0.86, p = 0.011) and high circulating Galectin-9 (HR 0.11, 95%CI 0.15–0.85, p = 0.010) levels were both associated with improved HCC-specific survival. Surprisingly, there was no correlation between circulating levels of PD-L1 and Galectin-9 and their intra-tumoral expression levels. In fact, circulating levels of PD-L1 and Galectin-9 were predictive of HCC-specific survival independently of intra-tumoral levels and baseline clinicopathologic characteristics. Combined analysis of circulating levels and intra-tumoral expression of PD-L1 (HR 0.33, 95%CI 0.16–0.68, p = 0.002) and Galectin-9 (HR 0.27, 95%CI 0.13–0.57, p = 0.001) resulted in more confident prediction of survival. In conclusion, circulating PD-L1 and Galectin-9 levels prognostically differentiate resected HCC patients, independently of their intra-tumoral expression. Combining circulating and intra-tumoral expression levels of PD-L1 or Galectin-9 further improves the prognostic values of these immune biomarkers.

AB - Tumor expression of immune co-inhibitory ligands, such as PD-L1 and Galectin-9, have potential prognostic value in Hepatocellular Carcinoma (HCC). Circulating levels of these molecules, however, have hardly been studied. This study aims to assess the prognostic significance of circulating PD-L1 and circulating Galectin-9 in patients with resected HCC, and to compare their prognostic significance to the intra-tumoral expression of these same molecules. Archived tissues and stored peripheral blood samples from 81 patients who underwent HCC resection or liver transplantation, with curative intent, were used. Immunohistochemistry was performed to determine intra-tumoral expression of PD-L1 and Galectin-9, while ELISA was used to quantify their respective circulating levels. High circulating PD-L1 (HR 0.12, 95%CI 0.16–0.86, p = 0.011) and high circulating Galectin-9 (HR 0.11, 95%CI 0.15–0.85, p = 0.010) levels were both associated with improved HCC-specific survival. Surprisingly, there was no correlation between circulating levels of PD-L1 and Galectin-9 and their intra-tumoral expression levels. In fact, circulating levels of PD-L1 and Galectin-9 were predictive of HCC-specific survival independently of intra-tumoral levels and baseline clinicopathologic characteristics. Combined analysis of circulating levels and intra-tumoral expression of PD-L1 (HR 0.33, 95%CI 0.16–0.68, p = 0.002) and Galectin-9 (HR 0.27, 95%CI 0.13–0.57, p = 0.001) resulted in more confident prediction of survival. In conclusion, circulating PD-L1 and Galectin-9 levels prognostically differentiate resected HCC patients, independently of their intra-tumoral expression. Combining circulating and intra-tumoral expression levels of PD-L1 or Galectin-9 further improves the prognostic values of these immune biomarkers.

UR - http://www.scopus.com/inward/record.url?scp=85069699900&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069699900&partnerID=8YFLogxK

U2 - 10.1038/s41598-019-47235-z

DO - 10.1038/s41598-019-47235-z

M3 - Article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 10677

ER -