High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic Metastasectomy

Considering the biology of CRC, distant metastases might support the identification of high-risk patients for early recurrence and targeted therapy. Expression of a panel of druggable, metastasis-related biomarkers was immunohistochemically analyzed in 53 liver (LM) and 15 lung metastases (LuM) and...

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Main Authors: Friederike Wrana, Katharina Dötzer, Martin Prüfer, Jens Werner, Barbara Mayer
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/8/1939
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author Friederike Wrana
Katharina Dötzer
Martin Prüfer
Jens Werner
Barbara Mayer
author_facet Friederike Wrana
Katharina Dötzer
Martin Prüfer
Jens Werner
Barbara Mayer
author_sort Friederike Wrana
collection DOAJ
description Considering the biology of CRC, distant metastases might support the identification of high-risk patients for early recurrence and targeted therapy. Expression of a panel of druggable, metastasis-related biomarkers was immunohistochemically analyzed in 53 liver (LM) and 15 lung metastases (LuM) and correlated with survival. Differential expression between LM and LuM was observed for the growth factor receptors IGF1R (LuM 92.3% vs. LM 75.8%, <i>p</i> = 0.013), EGFR (LuM 68% vs. LM 41.5%, <i>p</i> = 0.004), the cell adhesion molecules CD44v6 (LuM 55.7% vs. LM 34.9%, <i>p</i> = 0.019) and α2β1 (LuM 88.3% vs. LM 58.5%, <i>p</i> = 0.001) and the check point molecule PD-L1 (LuM 6.1% vs. LM 3.3%, <i>p</i> = 0.005). Contrary, expression of HGFR, Hsp90, Muc1, Her2/neu, ERα and PR was comparable in LuM and LM. In the LM cohort (<i>n</i> = 52), a high CD44v6 expression was identified as an independent factor of poor prognosis (PFS: HR 2.37, 95% CI 1.18–4.78, <i>p</i> = 0.016). High co-expression of CD44v6/α2β1 (HR 4.14, 95% CI 1.65–10.38, <i>p</i> = 0.002) and CD44v6/PD-L1 (HR 2.88, 95% CI 1.21–6.85, <i>p</i> = 0.017) indicated early recurrence after hepatectomy, in a substantial number of patients (CD44v6/α2β1: 11 (21.15%) patients; CD44v6/PD-L1: 12 (23.1%) patients). Dual expression of druggable protein biomarkers may refine prognostic prediction and stratify high-risk patients for new therapeutic concepts, depending on the metastatic location.
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spelling doaj.art-99a51b3c3c47472fbf335b35f8805dba2023-12-01T01:06:20ZengMDPI AGCancers2072-66942022-04-01148193910.3390/cancers14081939High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic MetastasectomyFriederike Wrana0Katharina Dötzer1Martin Prüfer2Jens Werner3Barbara Mayer4Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Marchioninistraße 15, 81377 Munich, GermanyDepartment of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Marchioninistraße 15, 81377 Munich, GermanyDepartment of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Marchioninistraße 15, 81377 Munich, GermanyDepartment of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Marchioninistraße 15, 81377 Munich, GermanyDepartment of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University, Marchioninistraße 15, 81377 Munich, GermanyConsidering the biology of CRC, distant metastases might support the identification of high-risk patients for early recurrence and targeted therapy. Expression of a panel of druggable, metastasis-related biomarkers was immunohistochemically analyzed in 53 liver (LM) and 15 lung metastases (LuM) and correlated with survival. Differential expression between LM and LuM was observed for the growth factor receptors IGF1R (LuM 92.3% vs. LM 75.8%, <i>p</i> = 0.013), EGFR (LuM 68% vs. LM 41.5%, <i>p</i> = 0.004), the cell adhesion molecules CD44v6 (LuM 55.7% vs. LM 34.9%, <i>p</i> = 0.019) and α2β1 (LuM 88.3% vs. LM 58.5%, <i>p</i> = 0.001) and the check point molecule PD-L1 (LuM 6.1% vs. LM 3.3%, <i>p</i> = 0.005). Contrary, expression of HGFR, Hsp90, Muc1, Her2/neu, ERα and PR was comparable in LuM and LM. In the LM cohort (<i>n</i> = 52), a high CD44v6 expression was identified as an independent factor of poor prognosis (PFS: HR 2.37, 95% CI 1.18–4.78, <i>p</i> = 0.016). High co-expression of CD44v6/α2β1 (HR 4.14, 95% CI 1.65–10.38, <i>p</i> = 0.002) and CD44v6/PD-L1 (HR 2.88, 95% CI 1.21–6.85, <i>p</i> = 0.017) indicated early recurrence after hepatectomy, in a substantial number of patients (CD44v6/α2β1: 11 (21.15%) patients; CD44v6/PD-L1: 12 (23.1%) patients). Dual expression of druggable protein biomarkers may refine prognostic prediction and stratify high-risk patients for new therapeutic concepts, depending on the metastatic location.https://www.mdpi.com/2072-6694/14/8/1939colorectal cancerliver metastaseslung metastasesprotein biomarkerdual expressionearly recurrence
spellingShingle Friederike Wrana
Katharina Dötzer
Martin Prüfer
Jens Werner
Barbara Mayer
High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic Metastasectomy
Cancers
colorectal cancer
liver metastases
lung metastases
protein biomarker
dual expression
early recurrence
title High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic Metastasectomy
title_full High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic Metastasectomy
title_fullStr High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic Metastasectomy
title_full_unstemmed High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic Metastasectomy
title_short High Dual Expression of the Biomarkers CD44v6/α2β1 and CD44v6/PD-L1 Indicate Early Recurrence after Colorectal Hepatic Metastasectomy
title_sort high dual expression of the biomarkers cd44v6 α2β1 and cd44v6 pd l1 indicate early recurrence after colorectal hepatic metastasectomy
topic colorectal cancer
liver metastases
lung metastases
protein biomarker
dual expression
early recurrence
url https://www.mdpi.com/2072-6694/14/8/1939
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