Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer
Abstract Background Though peritoneal carcinomatosis reflects a late stage of colorectal cancer (CRC), only few patients present with synchronous or metachronous liver metastases alongside their peritoneal carcinomatosis. It is hypothesized that this phenomenon may be causally linked to molecular ch...
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doaj-644022424f2048b2828671bde46b94a62020-11-24T21:07:27ZengBMCBMC Cancer1471-24072018-02-0118111010.1186/s12885-018-4043-0Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancerSabine Heublein0Markus Albertsmeier1David Pfeifer2Lisa Loehrs3Alexandr V. Bazhin4Thomas Kirchner5Jens Werner6Jens Neumann7Martin Kurt Angele8Department of General, Visceral, Transplantation and Vascular Surgery, University Hospital LMU MunichDepartment of General, Visceral, Transplantation and Vascular Surgery, University Hospital LMU MunichDepartment of General, Visceral, Transplantation and Vascular Surgery, University Hospital LMU MunichInstitute of Pathology, Ludwig-Maximilians-Universität MünchenDepartment of General, Visceral, Transplantation and Vascular Surgery, University Hospital LMU MunichInstitute of Pathology, Ludwig-Maximilians-Universität MünchenDepartment of General, Visceral, Transplantation and Vascular Surgery, University Hospital LMU MunichInstitute of Pathology, Ludwig-Maximilians-Universität MünchenDepartment of General, Visceral, Transplantation and Vascular Surgery, University Hospital LMU MunichAbstract Background Though peritoneal carcinomatosis reflects a late stage of colorectal cancer (CRC), only few patients present with synchronous or metachronous liver metastases alongside their peritoneal carcinomatosis. It is hypothesized that this phenomenon may be causally linked to molecular characteristics of the primary CRC. This study used miRNA profiling of primary CRC tissue either metastasized to the liver, to the peritoneum or not metastasized at all thus to identify miRNAs potentially associated with defining the site of metastatic spread in CRC. Methods Tissue of the primary tumor stemming from CRC patients diagnosed for either liver metastasis (LM; n = 10) or peritoneal carcinomatosis (PER; n = 10) was analyzed in this study. Advanced CRC cases without metastasis (M0; n = 3) were also included thus to select on those miRNAs most potentially associated with determining metastatic spread in general. miRNA profiling of 754 different miRNAs was performed in each group. MiRNAs being either differentially expressed comparing PER and LM or even triple differentially expressed (PER vs. LM vs. M0) were identified. Differentially expressed miRNAs were further validated by in silico and functional analysis. Results Comparative analysis identified 41 miRNAs to be differentially expressed comparing primary tumors metastasized to the liver as opposed to those spread to the peritoneum. A set of 31 miRNAs was significantly induced in primary tumors that spread to the peritoneum (PER), while the remaining 10 miRNAs were found to be repressed. Out of these 41 miRNAs a number of 25 miRNAs was triple-differentially expressed (i.e. differentially expressed comparing LM vs. PER vs. M0). The latter underwent in silico analysis. Finally, we demonstrated that miR-31 down-regulated c-MET in DLD-1 colon cancer cells. Conclusions This study demonstrates that CRC primary tumors spread to the peritoneum vs. metastasized to the liver display significantly different miRNA profiles. Larger patient cohorts will be needed to validate whether determination of e.g. miR-31 may aid to predict the course of disease and whether this may help to create individualized follow up or treatment protocols. To determine whether certain miRNAs may be involved in regulating the metastatic potential of CRC, functional studies will be essential.http://link.springer.com/article/10.1186/s12885-018-4043-0Colorectal cancermiRNAMetastasis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sabine Heublein Markus Albertsmeier David Pfeifer Lisa Loehrs Alexandr V. Bazhin Thomas Kirchner Jens Werner Jens Neumann Martin Kurt Angele |
spellingShingle |
Sabine Heublein Markus Albertsmeier David Pfeifer Lisa Loehrs Alexandr V. Bazhin Thomas Kirchner Jens Werner Jens Neumann Martin Kurt Angele Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer BMC Cancer Colorectal cancer miRNA Metastasis |
author_facet |
Sabine Heublein Markus Albertsmeier David Pfeifer Lisa Loehrs Alexandr V. Bazhin Thomas Kirchner Jens Werner Jens Neumann Martin Kurt Angele |
author_sort |
Sabine Heublein |
title |
Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer |
title_short |
Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer |
title_full |
Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer |
title_fullStr |
Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer |
title_full_unstemmed |
Association of differential miRNA expression with hepatic vs. peritoneal metastatic spread in colorectal cancer |
title_sort |
association of differential mirna expression with hepatic vs. peritoneal metastatic spread in colorectal cancer |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2018-02-01 |
description |
Abstract Background Though peritoneal carcinomatosis reflects a late stage of colorectal cancer (CRC), only few patients present with synchronous or metachronous liver metastases alongside their peritoneal carcinomatosis. It is hypothesized that this phenomenon may be causally linked to molecular characteristics of the primary CRC. This study used miRNA profiling of primary CRC tissue either metastasized to the liver, to the peritoneum or not metastasized at all thus to identify miRNAs potentially associated with defining the site of metastatic spread in CRC. Methods Tissue of the primary tumor stemming from CRC patients diagnosed for either liver metastasis (LM; n = 10) or peritoneal carcinomatosis (PER; n = 10) was analyzed in this study. Advanced CRC cases without metastasis (M0; n = 3) were also included thus to select on those miRNAs most potentially associated with determining metastatic spread in general. miRNA profiling of 754 different miRNAs was performed in each group. MiRNAs being either differentially expressed comparing PER and LM or even triple differentially expressed (PER vs. LM vs. M0) were identified. Differentially expressed miRNAs were further validated by in silico and functional analysis. Results Comparative analysis identified 41 miRNAs to be differentially expressed comparing primary tumors metastasized to the liver as opposed to those spread to the peritoneum. A set of 31 miRNAs was significantly induced in primary tumors that spread to the peritoneum (PER), while the remaining 10 miRNAs were found to be repressed. Out of these 41 miRNAs a number of 25 miRNAs was triple-differentially expressed (i.e. differentially expressed comparing LM vs. PER vs. M0). The latter underwent in silico analysis. Finally, we demonstrated that miR-31 down-regulated c-MET in DLD-1 colon cancer cells. Conclusions This study demonstrates that CRC primary tumors spread to the peritoneum vs. metastasized to the liver display significantly different miRNA profiles. Larger patient cohorts will be needed to validate whether determination of e.g. miR-31 may aid to predict the course of disease and whether this may help to create individualized follow up or treatment protocols. To determine whether certain miRNAs may be involved in regulating the metastatic potential of CRC, functional studies will be essential. |
topic |
Colorectal cancer miRNA Metastasis |
url |
http://link.springer.com/article/10.1186/s12885-018-4043-0 |
work_keys_str_mv |
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