ESMO 2025 | Placental signature identified in early-onset colorectal cancer

The young CRC study was an observational, prospective study, that we conducted across Italy and Spain, in which we collected samples from patients diagnosed with early-onset CRC aged younger than 45. From these patients, we were able to perform transcriptomic and proteomic analysis. From the latter, which was actually performed first, we were able to point out that early-onset colorectal cancer was characterized by the overexpression of a subset of placental proteins which were not observed in standard-onset colorectal cancer. And this was true even when we normalized our results on normal healthy mucosa adjacent to the tumor. Following this, by transcriptomic analysis, we were able to confirm this finding by observing the overexpression of erythrotransferrin, which is also called RVH, which is usually overexpressed only during pregnancy processes in humans. And even this overexpression was confirmed to be higher in early-onset CRC and instead lower in standard-onset cancer patients. Of course, these are preliminary results but derive from a very specific clinical patient population in which we focused on patients with sporadic early-onset CRC. Indeed, all those who had hereditary cancer predisposition syndromes or first-degree relatives diagnosed with CRC were excluded from this study. These features might retain translational potential in terms of drugability, but this is too early to say. We found preliminary results and we are going to validate these findings on both preclinical models established from the patients and on a larger cohort that we are collecting and collaborating with other groups from Italy, Spain, and even the United States of America.

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