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Evaluating macrophage migration inhibitory factor 1 expression as a prognostic biomarker in colon cancer

Olsson, Lina ; Lindmark, Gudrun LU ; Hammarström, Marie Louise ; Hammarström, Sten and Sitohy, Basel (2020) In Tumor Biology 42(6).
Abstract

Objective: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker. Methods: Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I–IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase–polymerase chain reaction. Expression of migration inhibitory factor 1 protein was investigated by two-color immunohistochemistry and immunomorphometry.... (More)

Objective: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker. Methods: Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I–IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase–polymerase chain reaction. Expression of migration inhibitory factor 1 protein was investigated by two-color immunohistochemistry and immunomorphometry. Results: Migration inhibitory factor 1 mRNA was expressed at 60 times higher levels in primary colon cancer tumors compared to normal colonic tissue (medians 8.2 and 0.2 mRNA copies/18S rRNA unit; p <.0001). A highly significant difference in mRNA expression levels was found between hematoxylin-eosin positive lymph nodes and hematoxylin-eosin negative lymph nodes (p <.0001). Migration inhibitory factor 1 and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer-tumor cells. Kaplan–Meier survival model and hazard ratio analysis, using a cutoff level at 2.19 mRNA copies/18S rRNA unit, revealed that patients with lymph nodes expressing high levels of migration inhibitory factor 1 mRNA had a 3.5-fold (p =.04) higher risk for recurrence, associated with a small, but significant, difference in mean survival time (7 months, p =.03) at 12 years of follow-up. Conclusion: Although migration inhibitory factor 1 mRNA expression levels were related to severity of disease and lymph node analysis revealed that colon cancer patients with high levels had a shorter survival time after surgery than those with low levels, the difference was small and probably not useful in clinical practice.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
carcinoembryonic antigen, colon cancer, cumulative survival curves; recurrence risk, disseminated tumor cells, immunofluorescence, immunohistochemistry, immunomorphometry, Macrophage migration inhibitory factor, quantitative reverse transcriptase–polymerase chain reaction
in
Tumor Biology
volume
42
issue
6
publisher
Springer
external identifiers
  • pmid:32515296
  • scopus:85086257481
ISSN
1010-4283
DOI
10.1177/1010428320924524
language
English
LU publication?
yes
id
987cd8b4-0736-43ae-8318-0eced1f1c664
date added to LUP
2020-06-30 15:43:13
date last changed
2020-07-01 05:34:49
@article{987cd8b4-0736-43ae-8318-0eced1f1c664,
  abstract     = {<p>Objective: Several studies indicate that macrophage migration inhibitory factor 1 plays a role for tumor progression in colon cancer. We investigated whether determination of migration inhibitory factor 1 mRNA expression levels in lymph nodes of colon cancer patients could be used as a prognostic marker. Methods: Expression levels of migration inhibitory factor 1 and carcinoembryonic antigen mRNAs were assessed in primary tumors and regional lymph nodes of 123 colon cancer patients (stages I–IV), and in colon cancer- and immune cell lines using quantitative reverse transcriptase–polymerase chain reaction. Expression of migration inhibitory factor 1 protein was investigated by two-color immunohistochemistry and immunomorphometry. Results: Migration inhibitory factor 1 mRNA was expressed at 60 times higher levels in primary colon cancer tumors compared to normal colonic tissue (medians 8.2 and 0.2 mRNA copies/18S rRNA unit; p &lt;.0001). A highly significant difference in mRNA expression levels was found between hematoxylin-eosin positive lymph nodes and hematoxylin-eosin negative lymph nodes (p &lt;.0001). Migration inhibitory factor 1 and carcinoembryonic antigen proteins were simultaneously expressed in many colon cancer-tumor cells. Kaplan–Meier survival model and hazard ratio analysis, using a cutoff level at 2.19 mRNA copies/18S rRNA unit, revealed that patients with lymph nodes expressing high levels of migration inhibitory factor 1 mRNA had a 3.5-fold (p =.04) higher risk for recurrence, associated with a small, but significant, difference in mean survival time (7 months, p =.03) at 12 years of follow-up. Conclusion: Although migration inhibitory factor 1 mRNA expression levels were related to severity of disease and lymph node analysis revealed that colon cancer patients with high levels had a shorter survival time after surgery than those with low levels, the difference was small and probably not useful in clinical practice.</p>},
  author       = {Olsson, Lina and Lindmark, Gudrun and Hammarström, Marie Louise and Hammarström, Sten and Sitohy, Basel},
  issn         = {1010-4283},
  language     = {eng},
  number       = {6},
  publisher    = {Springer},
  series       = {Tumor Biology},
  title        = {Evaluating macrophage migration inhibitory factor 1 expression as a prognostic biomarker in colon cancer},
  url          = {http://dx.doi.org/10.1177/1010428320924524},
  doi          = {10.1177/1010428320924524},
  volume       = {42},
  year         = {2020},
}