High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern

To date, nearly one-quarter of colorectal cancer (CRC) patients develop liver metastases (CRCLM), and its aggressiveness can be correlated to defined histopathological growth patterns (HGP). From the three main HGPs within CRCLM, the replacement HGP emerges as particularly aggressive, characterized...

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Main Authors: Shuang Fan, Johannes Robert Fleischer, Lolita Dokshokova, Lena Sophie Böhme, Gwendolyn Haas, Alexandra Maria Schmitt, Fabio Bennet Gätje, Linde-Allegra Emmalie Rosen, Hanibal Bohnenberger, Michael Ghadimi, Baolong Cui, Xingbo Xu, Joanna Maria Kalucka, Florian Bösch, Tiago De Oliveira, Lena-Christin Conradi
Format: Article
Language:English
Published: Elsevier 2024-09-01
Series:Molecular Therapy: Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950329924000705
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author Shuang Fan
Johannes Robert Fleischer
Lolita Dokshokova
Lena Sophie Böhme
Gwendolyn Haas
Alexandra Maria Schmitt
Fabio Bennet Gätje
Linde-Allegra Emmalie Rosen
Hanibal Bohnenberger
Michael Ghadimi
Baolong Cui
Xingbo Xu
Joanna Maria Kalucka
Florian Bösch
Tiago De Oliveira
Lena-Christin Conradi
author_facet Shuang Fan
Johannes Robert Fleischer
Lolita Dokshokova
Lena Sophie Böhme
Gwendolyn Haas
Alexandra Maria Schmitt
Fabio Bennet Gätje
Linde-Allegra Emmalie Rosen
Hanibal Bohnenberger
Michael Ghadimi
Baolong Cui
Xingbo Xu
Joanna Maria Kalucka
Florian Bösch
Tiago De Oliveira
Lena-Christin Conradi
author_sort Shuang Fan
collection DOAJ
description To date, nearly one-quarter of colorectal cancer (CRC) patients develop liver metastases (CRCLM), and its aggressiveness can be correlated to defined histopathological growth patterns (HGP). From the three main HGPs within CRCLM, the replacement HGP emerges as particularly aggressive, characterized by heightened tumor cell motility and vessel co-option. Here, we investigated the correlation between the expression of calcium- and integrin-binding protein 1 (CIB1), a ubiquitously expressed gene involved in various cellular processes including migration and adhesion, and disease-free (DFS) and overall survival (OS) in primary CRC patients. Additionally, we explored the correlation between CIB1 expression and different HGPs of CRCLM. Proteomic analysis was used to evaluate CIB1 expression in a cohort of 697 primary CRC patients. Additionally, single-cell and spatial RNA-sequencing datasets, along with publicly available bulk sequencing data were used to evaluate CIB1 expression in CRCLM. In silico data were further validated by formalin-fixed paraffin-embedded immunohistochemical stainings. We observed that high CIB1 expression is independently associated with worse DFS and OS, regardless of Union Internationale Contre le Cancer stage, gender, or age. Furthermore, the aggressive replacement CRCLM HGP is significantly associated with high CIB1 expression. Our findings show a correlation between CIB1 levels and the clinical aggressiveness of CRC. Moreover, CIB1 may be a novel marker to stratify HGP CRCLM.
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spelling doaj-art-c539c50a884b4584abbcd6a6df1dbe2a2025-08-20T02:22:32ZengElsevierMolecular Therapy: Oncology2950-32992024-09-0132320082810.1016/j.omton.2024.200828High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth patternShuang Fan0Johannes Robert Fleischer1Lolita Dokshokova2Lena Sophie Böhme3Gwendolyn Haas4Alexandra Maria Schmitt5Fabio Bennet Gätje6Linde-Allegra Emmalie Rosen7Hanibal Bohnenberger8Michael Ghadimi9Baolong Cui10Xingbo Xu11Joanna Maria Kalucka12Florian Bösch13Tiago De Oliveira14Lena-Christin Conradi15Department of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyDepartment of Biomedicine, Aarhus University, Hegh-Guldbergsgade 10, 8000 Aarhus C, DenmarkDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyInstitute of Pathology, University Medical Center Göttingen, Göttingen, GermanyDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyDepartment of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Cardiology and Pneumology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Biomedicine, Aarhus University, Hegh-Guldbergsgade 10, 8000 Aarhus C, DenmarkDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, GermanyDepartment of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, Germany; Corresponding author: Lena-Christin Conradi, PhD, Department of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, Germany.To date, nearly one-quarter of colorectal cancer (CRC) patients develop liver metastases (CRCLM), and its aggressiveness can be correlated to defined histopathological growth patterns (HGP). From the three main HGPs within CRCLM, the replacement HGP emerges as particularly aggressive, characterized by heightened tumor cell motility and vessel co-option. Here, we investigated the correlation between the expression of calcium- and integrin-binding protein 1 (CIB1), a ubiquitously expressed gene involved in various cellular processes including migration and adhesion, and disease-free (DFS) and overall survival (OS) in primary CRC patients. Additionally, we explored the correlation between CIB1 expression and different HGPs of CRCLM. Proteomic analysis was used to evaluate CIB1 expression in a cohort of 697 primary CRC patients. Additionally, single-cell and spatial RNA-sequencing datasets, along with publicly available bulk sequencing data were used to evaluate CIB1 expression in CRCLM. In silico data were further validated by formalin-fixed paraffin-embedded immunohistochemical stainings. We observed that high CIB1 expression is independently associated with worse DFS and OS, regardless of Union Internationale Contre le Cancer stage, gender, or age. Furthermore, the aggressive replacement CRCLM HGP is significantly associated with high CIB1 expression. Our findings show a correlation between CIB1 levels and the clinical aggressiveness of CRC. Moreover, CIB1 may be a novel marker to stratify HGP CRCLM.http://www.sciencedirect.com/science/article/pii/S2950329924000705MT: Regular IssueCIB1colorectal cancerhistopathological growth patterns of liver metastasissingle-cell RNA sequencingspatial transcriptomics
spellingShingle Shuang Fan
Johannes Robert Fleischer
Lolita Dokshokova
Lena Sophie Böhme
Gwendolyn Haas
Alexandra Maria Schmitt
Fabio Bennet Gätje
Linde-Allegra Emmalie Rosen
Hanibal Bohnenberger
Michael Ghadimi
Baolong Cui
Xingbo Xu
Joanna Maria Kalucka
Florian Bösch
Tiago De Oliveira
Lena-Christin Conradi
High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern
Molecular Therapy: Oncology
MT: Regular Issue
CIB1
colorectal cancer
histopathological growth patterns of liver metastasis
single-cell RNA sequencing
spatial transcriptomics
title High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern
title_full High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern
title_fullStr High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern
title_full_unstemmed High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern
title_short High CIB1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern
title_sort high cib1 expression in colorectal cancer liver metastases correlates with worse survival and the replacement histopathological growth pattern
topic MT: Regular Issue
CIB1
colorectal cancer
histopathological growth patterns of liver metastasis
single-cell RNA sequencing
spatial transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2950329924000705
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