The diagnostic performance of molecular markers in surrogate tissues like stool may be affected by colorectal cancer (CRC) morphological heterogeneity. The mucinous histotype represents a subgroup of CRC with a peculiar molecular program and unfavorable disease progression. However, the percentage of mucinous morphology necessary to define this subtype is still a matter of debate. In this study, we investigated whether stool miRNA profiles of CRC patients differ in patients with mucinous histopathological subtypes compared to non-mucinous cancers. In this respect, we also explored how the stool miRNA signature reported in our previous multicentric study behaves in this histotype. Small-RNA sequencing was performed in fecal and tissue samples of an Italian cohort (n = 172), including 27 CRC with mucinous morphology (mucinous cancers with ≥ 50% mucinous morphology and those with mucinous component ≥ 5% but < 50%), 58 non-mucinous CRC, and 87 colonoscopy-negative controls. Results were compared with fecal miRNA profiles of a cohort from the Czech Republic (n = 98). Most of the differentially expressed (DE) stool miRNAs (n = 324) were in common between CRC with mucinous morphology and non-mucinous histopathological subtypes in comparison with healthy controls. Interestingly, the altered levels of 25 fecal miRNAs previously identified distinguishing CRC cases from controls in both cohorts were also confirmed after stratification for mucinous morphology. Forty-nine miRNAs were DE exclusively in CRC with mucinous morphology and 61 in non-mucinous CRC. Mucinous cancers and those with mucinous component showed fairly similar profiles that were comparable in the Czech cohort. Among the stool DE miRNAs observed in CRC with mucinous morphology, 20 were also altered in the comparison between tumor and adjacent mucosa tissue. This study highlights miRNAs specifically altered in CRC with mucinous morphology. Nevertheless, the performance of our stool miRNA signature in accurately distinguishing CRC cases from controls was not significantly affected by this histological subtype. This aspect further supports the use of stool miRNAs for noninvasive diagnosis and screening strategies.

Berlin Institute of Health at Charit´e Universit¨atsmedizin Berlin Charit´eplatz 1 10117 Berlin Germany

Biomedical Centre Faculty of Medicine in Pilsen Charles University Pilsen 32300 Czech Republic

Candiolo Cancer Institute FPO IRCCS Candiolo 10060 Turin Italy

Department of Clinical and Biological Sciences University of Torino Turin 10100 Italy

Department of Colorectal Surgery Clinica S Rita Vercelli 13100 Italy

Department of Molecular Biology of Cancer Institute of Experimental Medicine of the Czech Academy of Sciences Prague 14220 Czech Republic

Department of Oncology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague 150 06 Czech Republic

Department of Surgery La Sapienza University of Rome Rome 00161 Italy

Department of Surgery University Hospital and Faculty of Medicine in Pilsen Charles University Pilsen 32300 Czech Republic

Genetic and Molecular Epidemiology Unit Italian Institute for Genomic Medicine c o IRCCS Candiolo Candiolo 10060 Turin Italy

German Cancer Consortium Heidelberg 69120 Germany

Institute of Biology and Medical Genetics 1st Medical Faculty Charles University Prague 12800 Czech Republic

Institute of Pathology Charité Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin Humboldt Universität zu Berlin Berlin 10117 Germany

Citace poskytuje Crossref.org

Commentary: Special Issue: Current Understanding of Colorectal and Pancreatic Cancers