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

Abstract

To date, nearly one-quarter of 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 CIB1, an 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 HGP 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 a publicly available bulk sequencing data were used to evaluate CIB1 expression in CRCLM. In silico data was further validate by FFPE immunohistochemical stainings. We observed that high CIB1 expression is independently associated with worse DFS and OS, regardless of UICC 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.