Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment
Abstract Background Colorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases. Aims Studying the expression and cellular function of miR‐18a in metastatic colorectal cancer and association to progress...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-12-01
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| Series: | Cancer Reports |
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| Online Access: | https://doi.org/10.1002/cnr2.1899 |
| _version_ | 1797344673937752064 |
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| author | Clemens Franz Laila Jötten Michael Wührl Sibylle Hartmann Fee Klupp Thomas Schmidt Martin Schneider |
| author_facet | Clemens Franz Laila Jötten Michael Wührl Sibylle Hartmann Fee Klupp Thomas Schmidt Martin Schneider |
| author_sort | Clemens Franz |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases. Aims Studying the expression and cellular function of miR‐18a in metastatic colorectal cancer and association to progression‐free survival. Methods and Results Colorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT‐PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR‐18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR‐18a was increased 4.38‐fold in liver metastases and 3.86‐fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR‐18a expression in liver metastases had a progression‐free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR‐18a knockdown and cell viability was significantly increased after miR‐18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR‐18a expression receiving 5‐FU, folinic acid or oxaliplatin. Conclusions High expression of miR‐18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS. |
| first_indexed | 2024-03-08T11:06:09Z |
| format | Article |
| id | doaj.art-3ccfe4deffda42979ab325cb6a8a70af |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-03-08T11:06:09Z |
| publishDate | 2023-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-3ccfe4deffda42979ab325cb6a8a70af2024-01-26T14:41:21ZengWileyCancer Reports2573-83482023-12-01612n/an/a10.1002/cnr2.1899Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatmentClemens Franz0Laila Jötten1Michael Wührl2Sibylle Hartmann3Fee Klupp4Thomas Schmidt5Martin Schneider6Department of General, Visceral and Transplant Surgery University Hospital Heidelberg Heidelberg GermanyDepartment of General, Visceral and Transplant Surgery University Hospital Heidelberg Heidelberg GermanyDepartment of General, Visceral and Transplant Surgery University Hospital Heidelberg Heidelberg GermanyDepartment of General, Visceral and Transplant Surgery University Hospital Heidelberg Heidelberg GermanyDepartment of General, Visceral and Transplant Surgery University Hospital Heidelberg Heidelberg GermanyDepartment of General, Visceral and Transplant Surgery University Hospital Heidelberg Heidelberg GermanyDepartment of General, Visceral and Transplant Surgery University Hospital Heidelberg Heidelberg GermanyAbstract Background Colorectal cancer ranks second in terms of cancer associated deaths worldwide, whereas miRNA play a pivotal role in the etiology of cancer and its metastases. Aims Studying the expression and cellular function of miR‐18a in metastatic colorectal cancer and association to progression‐free survival. Methods and Results Colorectal liver metastases (N = 123) and primary colorectal cancer (N = 27) where analyzed by RT‐PCR and correlated with clinical follow up data. Invasion and migration assays were performed with the liver metastatic cell line LIM2099 after miR‐18a knockdown. Cell viability under FOLFOX treatment and knockdown was measured. We found that the expression of miR‐18a was increased 4.38‐fold in liver metastases and 3.86‐fold in colorectal tumor tissue compared to healthy liver tissue and colorectal mucosa, respectively (p ≤ .001). Patients with a high miR‐18a expression in liver metastases had a progression‐free survival (PFS) of 13.6 months versus 8.9 months in patients with low expression (N = 123; p = .024). In vitro migration of LIM2099 cells was reduced after miR‐18a knockdown and cell viability was significantly increased after miR‐18a knockdown and treatment with folinic acid or oxaliplatin. Subgroup analysis of PFS revealed significant benefits for patients with high miR‐18a expression receiving 5‐FU, folinic acid or oxaliplatin. Conclusions High expression of miR‐18a in colorectal liver metastases might have a protective effect after resection of metastases and FOLFOX treatment regarding PFS.https://doi.org/10.1002/cnr2.1899colorectal cancerFOLFOX protocolhepatectomyMicroRNAsneoplasm metastasis |
| spellingShingle | Clemens Franz Laila Jötten Michael Wührl Sibylle Hartmann Fee Klupp Thomas Schmidt Martin Schneider Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment Cancer Reports colorectal cancer FOLFOX protocol hepatectomy MicroRNAs neoplasm metastasis |
| title | Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment |
| title_full | Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment |
| title_fullStr | Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment |
| title_full_unstemmed | Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment |
| title_short | Protective effect of miR‐18a in resected liver metastases of colorectal cancer and FOLFOX treatment |
| title_sort | protective effect of mir 18a in resected liver metastases of colorectal cancer and folfox treatment |
| topic | colorectal cancer FOLFOX protocol hepatectomy MicroRNAs neoplasm metastasis |
| url | https://doi.org/10.1002/cnr2.1899 |
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