In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 80, No. 16_Supplement ( 2020-08-15), p. 257-257
Abstract:
Colorectal cancer (CRC) ranks as the second most common non-sex-specific cancer worldwide and the second cause of cancer deaths. Screening programs for CRC based on the fecal immunochemical test (FIT) are effective in average-risk population for the tumor detection but has low sensitivity for the recognition of advanced adenomas. We identified microRNA (miRNA) signatures by next-generation sequencing in fecal samples that could detect patients with adenomas or CRC. The same signatures were also evaluated in plasma extracellular vesicles (EVs) from the same patients. A genome-wide miRNA expression profiling was initially performed in 221 subjects (80 healthy subjects; 43 adenoma patients; 41 individuals with inflammatory bowel disease [IBD]; and 57 CRC) recruited in a cross-sectional study in Italy where stool and plasma samples have been consecutively collected at colonoscopy. Several differentially expressed miRNAs, mostly in stool samples, have been identified both in common or peculiar of specific comparison among the 3 categories of patients vs healthy subjects. Subsequently, a similar profiling has been performed for a set of 24 paired colorectal tumor and adjacent non-tumor samples from the group of CRC patients already samples for stool and plasma. Several miRNAs (n=137) resulted altered in cancer tissues compared to non-tumor; on the other hand, 91 miRNAs resulted altered in stool and only 6 in plasma EVs. Analyzing stool samples from the whole Italian cohort we observed a good overlap of the altered miRNAs observed in tissues (miR-148a-3p, miR-182-5p, miR-143-3p, miR-12136-3p; miR-378a-3p, miR-1290-5p, miR-21-5p, miR-7704-3p). The identified differentially expressed miRNAs in stool and plasma EVs were validated in an independent cohort from the Czech Republic (22 healthy, 19 Inflammation, 21 Adenoma, 34 CRC) with a similar approach. Preliminary results in this independent cohort showed that 19, 12 and 7 miRNAs were differentially expressed when comparing CRC with healthy, CRC and adenoma and inflammation individuals, respectively. In the comparison of CRC versus healthy subjects we observed a good overlap of miRNAs differentially expressed between the Czech and Italian cohorts: 10 miRNAs (miR-148a-3p, miR-1181-3p, miR-1290-5p, miR-4488-3p, miR-1246-3p, let-7i-5p, let-7b-5p, miR-4497-3p, miR-21-5p, miR-149-3p) were significantly altered in the same directions in the 2 cohorts. Moreover, hsa-miR-1290-5p and hsa-miR-4488-3p resulted significantly upregulated when going from healthy, inflammation, adenoma and CRC both in the Italian and in the Czech cohorts. Finally, with the application of a multi-class machine learning approach, we identified a signature of 13 miRNAs whose expression was able to accurately classify (AUC = 0.90) the four classes of subjects in combination with the information of patient age and sex. These results showed that there could be a potential application of the analyses of nucleic acids in stool as adjuvant in non-invasive screening. Citation Format: Sonia Tarallo, Antonio Francavilla, Giulio Ferrero, Francesca Cordero, Gaetano Gallo, Andrew Maltez Thomas, Paolo Manghi, Veronika Vymetalkova, Ludmila Vodickova, Nicola Segata, Pavel Vodicka, Barbara Pardini, Alessio Naccarati. Whole miRNome profiling in fecal and plasma exosome samples for the diagnosis of colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 257.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2020-257
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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