Patients with mixed tumours are those patients who had had multiple liver tumours with different dominant growth patterns. We divided our patients into three groups of HGPs as follows: predominant vessel co-opting RHGP (44.4%), predominant angiogenic DHGP (34.3%), and mixed (21.3%), as shown in Table 1. Of note, the HGPs of the tumours were scored by histopathologists using 50% cut-off predominant HGPs scoring following international consensus guidelines for scoring the HGPs of liver metastasis. Next, we categorized both populations according to the HGPs of their tumours.

We established a local cohort of CRCLM from 108 patients ( Supplementary Table S1) and categorized patients based on their usage of metformin 20 (18.5%) of the patients used metformin and 88 patients (81.5%) did not use metformin. Collectively, our data suggest that metformin administration is likely associated with better prognosis of CRCLM. Moreover, the metformin user patients had significantly higher survival outcome compared to nonusers. Similar results were obtained when we compared the ratio of recurrence and extrahepatic metastases incidence. We noticed a significantly lower percentage of CRCLM patients with vessel co-opting RHGP tumours in the population that used metformin compared to CRCLM patients who did not use metformin. The metformin user patients did not use metformin as an anticancer agent. A dataset of 108 patients was screened, of which 20 patients used metformin. Herein, we conducted a retrospective cohort study to examine the role of metformin in CRCLM. However, its role in CRCLM is poorly understood. Metformin has been shown to influence the progression and vasculature of tumours in different cancers. The presence of vessel co-option tumours is associated with poor response to anti-angiogenic agents and chemotherapy, as well as a worse prognosis. The vascularization in DHGP tumours is angiogenic, while the RHGP tumours exert vessel co-option vasculature. Colorectal cancer liver metastases (CRCLMs) have two main histopathological growth patterns (HPGs): desmoplastic (DHGP) and replacement (RHGP).

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