Number of the records: 1
Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer
- 1.
SYSNO ASEP 0577150 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Differences in genome, transcriptome, miRNAome, and methylome in synchronous and metachronous liver metastasis of colorectal cancer Author(s) Horák, Josef (UEM-P) ORCID
Kubeček, O. (CZ)
Šišková, Anna (UEM-P)
Hoňková, Kateřina (UEM-P)
Chvojková, Irena (UEM-P)
Krupová, M. (CZ)
Manethová, M. (CZ)
Vodenková, Soňa (UEM-P) ORCID, RID
Garcia-Mulero, S. (ES)
John, S. (CZ)
Cecka, F. (CZ)
Vodičková, Ludmila (UEM-P) RID
Petera, J. (CZ)
Filip, S. (CZ)
Vymetálková, Veronika (UEM-P) RIDArticle number 1133598 Source Title Frontiers in Oncology. - : Frontiers Research Foundation - ISSN 2234-943X
Roč. 13, apr. (2023)Number of pages 29 s. Language eng - English Country CH - Switzerland Keywords colorectal cancer ; MiRNAome ; methylome ; transcriptome ; liver metastasis OECD category Biochemistry and molecular biology R&D Projects NV19-09-00237 GA MZd - Ministry of Health (MZ) LX22NPO5102 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2018124 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001821 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UEM-P - RVO:68378041 UT WOS 000985791800001 EID SCOPUS 85159075962 DOI 10.3389/fonc.2023.1133598 Annotation Despite distant metastases being the critical factor affecting patients' survival, they remain poorly understood. Our study thus aimed to molecularly characterize colorectal cancer liver metastases (CRCLMs) and explore whether molecular profiles differ between Synchronous (SmCRC) and Metachronous (MmCRC) colorectal cancer. This characterization was performed by whole exome sequencing, whole transcriptome, whole methylome, and miRNAome. The most frequent somatic mutations were in APC, SYNE1, TP53, and TTN genes. Among the differently methylated and expressed genes were those involved in cell adhesion, extracellular matrix organization and degradation, neuroactive ligand-receptor interaction. The top up-regulated microRNAs were hsa-miR-135b-3p and -5p, and the hsa-miR-200-family while the hsa-miR-548-family belonged to the top down-regulated. MmCRC patients evinced higher tumor mutational burden, a wider median of duplications and deletions, and a heterogeneous mutational signature than SmCRC. Regarding chronicity, a significant down-regulation of SMOC2 and PPP1R9A genes in SmCRC compared to MmCRC was observed. Two miRNAs were deregulated between SmCRC and MmCRC, hsa-miR-625-3p and has-miR-1269-3p. The combined data identified the IPO5 gene. Regardless of miRNA expression levels, the combined analysis resulted in 107 deregulated genes related to relaxin, estrogen, PI3K-Akt, WNT signaling pathways, and intracellular second messenger signaling. The intersection between our and validation sets confirmed the validity of our results. We have identified genes and pathways that may be considered as actionable targets in CRCLMs. Our data also provide a valuable resource for understanding molecular distinctions between SmCRC and MmCRC. They have the potential to enhance the diagnosis, prognostication, and management of CRCLMs by a molecularly targeted approach. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2024 Electronic address https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1133598/full
Number of the records: 1