Fan Shuang, Fleischer Johannes Robert, Dokshokova Lolita, Böhme Lena Sophie, Haas Gwendolyn, Schmitt Alexandra Maria, Gätje Fabio Bennet, Rosen Linde-Allegra Emmalie, Bohnenberger Hanibal, Ghadimi Michael, Cui Baolong, Xu Xingbo, Kalucka Joanna Maria, Bösch Florian, De Oliveira Tiago, Conradi Lena-Christin
Department of General, Visceral and Paediatric Surgery, University Medical Center Göttingen, Robert-Koch-Straβe 40, 37075 Göttingen, Germany.
Department of Biomedicine, Aarhus University, Hegh-Guldbergsgade 10, 8000 Aarhus C, Denmark.
Mol Ther Oncol. 2024 Jun 9;32(3):200828. doi: 10.1016/j.omton.2024.200828. eCollection 2024 Sep 19.
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. 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 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.
迄今为止，近四分之一的结直肠癌（CRC）患者会发生肝转移（CRCLM），其侵袭性与特定的组织病理学生长模式（HGP）相关。在CRCLM的三种主要HGP中，替代型HGP表现出特别强的侵袭性，其特征是肿瘤细胞运动性增强和血管共选择。在此，我们研究了钙和整合素结合蛋白1（CIB1）的表达与原发性CRC患者无病生存期（DFS）和总生存期（OS）之间的相关性，CIB1是一种普遍表达的基因，参与包括迁移和黏附在内的各种细胞过程。此外，我们还探讨了CIB1表达与CRCLM不同HGP之间的相关性。蛋白质组学分析用于评估697例原发性CRC患者队列中的CIB1表达。此外，单细胞和空间RNA测序数据集以及公开可用的批量测序数据用于评估CRCLM中的CIB1表达。数据通过福尔马林固定石蜡包埋免疫组化染色进一步验证。我们观察到，无论分期、性别或年龄如何，高CIB1表达均与较差的DFS和OS独立相关。此外，侵袭性的替代型CRCLM HGP与高CIB1表达显著相关。我们的研究结果表明CIB1水平与CRC的临床侵袭性之间存在相关性。此外，CIB1可能是一种对CRCLM的HGP进行分层的新型标志物。
