Fecal miRNA profiles in colorectal cancers with mucinous morphology.

IF 2.5 4区 医学 Q3 GENETICS & HEREDITY Mutagenesis Pub Date : 2024-06-06 DOI:10.1093/mutage/geae015
Alessio Naccarati, Mihnea P Dragomir, Sonia Tarallo, Amedeo Gagliardi, Virginia Alberini, Tomas Buchler, Vaclav Liska, Gaetano Gallo, Veronika Vymetalkova, Ludmila Vodickova, Pavel Vodicka, Barbara Pardini, Giulio Ferrero
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Abstract

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 (Pardini et al., Gastroenterology 2023) behave 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.

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具有粘液形态的结直肠癌的粪便 miRNA 图谱。
大肠癌(CRC)形态异质性可能会影响粪便等替代组织中分子标记物的诊断性能。粘液组织型代表了具有特殊分子程序和不利疾病进展的 CRC 亚群。然而,定义这一亚型所需的粘液形态比例仍存在争议。在这项研究中,我们调查了与非黏液性癌症相比,黏液性组织病理学亚型 CRC 患者的粪便 miRNA 图谱是否有所不同。在这方面,我们还探讨了我们之前的多中心研究(Pardini 等人,《胃肠病学》2023 年版)中报告的粪便 miRNA 特征在这种组织类型中的表现。我们对一个意大利队列(n=172)的粪便和组织样本进行了小分子 RNA 测序,其中包括 27 例具有粘液形态的 CRC(粘液形态>50%的粘液癌和粘液成分>5%但不包括非粘液癌)。
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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
期刊介绍: Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.
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