Abstract 460: Fecal microRNA and microbiome profiles in colorectal cancer patients: Are they predictor of survival and how do behave in longitudinal samples

Abstract Background: Colorectal cancer (CRC) is characterized by a high complexity that significantly influences treatment response and survival. There is still a lack of prognostic factors after surgery that could help predict postoperative survival. Currently, lymph node metastases are the single most important prognostic factor but it gives no clue on tumor aggressiveness and recurrence. Our group recently contributed to the identification of a fecal microRNA (miRNA) signature that accurately discriminates sporadic CRC and aimed at improving non-invasive diagnosis (Pardini et al, Gastroenterology 2023) as well as altered gut microbiome species associated with CRC (Thomas et al, Nat. Medicine 2019), but there are scanty evidence on the potentiality of such markers for prognosis. Aims: In the same cohort, we investigated if the fecal miRNome and gut microbiome at diagnosis are associated with CRC patients’ prognosis. Moreover, we assessed fecal miRNA in a new set of CRC patients collected longitudinally before and after the surgery to investigate whether such associations reflect miRNA profiles over time. Methods. We performed small RNA and shotgun metagenomic sequencing in stool samples in 3 cohorts from: Italy (IT, 128 CRC), Czech Republic (CZ, 69 CRC), and Turkey (TU, 34 CRC, 40 controls). Stool samples from TU CRC subjects were collected before surgery and after 6 months. Preliminary Results: In the IT and CZ cohorts, an average of 479 fecal miRNAs were detected with 209 differentially expressed (DE) miRNAs significantly associated with survival, including miR-1246 which was present in the CRC-associated signature identified by us. Two miRNAs (miR-197-5p and miR-6081-5p) were significantly down-regulated in patients with the worst prognosis (adj.p<0.01, HR<0.50) in both cohorts. In TU cohort, 494 miRNAs were DE in CRC (pre-surgery) vs controls. Among them, the 25 DE miRNAs detected in our previous work were also significantly altered, including the 5-miRNA CRC signature (miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p) identified by machine learning. Notably, after 6 months from surgery, levels of such miRNAs reverted to those measured in controls (for miR-1246 p<0.001 in both controls vs pre- and vs post-surgery comparisons). More analyses on the longitudinal fecal miRNA data are ongoing as well as for the metagenome data assessing the abundancies of CRC-associated microbial species before and after tumor resection and their possible association with survival. Conclusions: Fecal miRNAs may serve as biomarkers for CRC prognosis. Following tumor resection, CRC levels of altered miRNAs return in a range comparable with those of healthy controls in a time-dependent manner. These data further support the use of fecal miRNAs as accurate diagnostic CRC biomarkers and provide preliminary information on their possible translation as a prognostic tool. Citation Format: Barbara Pardini, Nazim Arda Keles, Giulio Ferrero, Sonia Tarallo, Giulia Francescato, Amedeo Gagliardi, Virginia Alberini, Carla Di Battista, Veronika Vymetalkova, Fatma Turkoglu, Ozgul Duzgun, Omer Faruk Ozkan, Bilge Guvenc Tuna, Pavel Vodicka, Soner Dogan, Alessio Naccarati. Fecal microRNA and microbiome profiles in colorectal cancer patients: Are they predictor of survival and how do behave in longitudinal samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 460.