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Clinical significance of stem cell biomarkers epcam, lgr5 and lgr4 mrna levels in lymph nodes of colon cancer patients

Abdelmageed, Manar ; Ismail, Hager Tarek H. ; Olsson, Lina ; Lindmark, Gudrun LU ; Hammarström, Marie Louise ; Hammarström, Sten and Sitohy, Basel (2022) In International Journal of Molecular Sciences 23(1).
Abstract

The significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients. Expression levels were determined in 5 CC cell lines, 66 primary CC tumors and 382 regional lymph nodes of 121 CC patients. Prognostic relevance was determined using Kaplan‐Meier survival and Cox regression analyses. CC patients with lymph nodes expressing high levels of EpCAM, LGR5 or LGR4 (higher than a clinical cutoff of 0.07, 0.06 and 2.558 mRNA cop-ies/18S rRNA unit, respectively) had a decreased mean survival time of 32 months for EpCAM... (More)

The significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients. Expression levels were determined in 5 CC cell lines, 66 primary CC tumors and 382 regional lymph nodes of 121 CC patients. Prognostic relevance was determined using Kaplan‐Meier survival and Cox regression analyses. CC patients with lymph nodes expressing high levels of EpCAM, LGR5 or LGR4 (higher than a clinical cutoff of 0.07, 0.06 and 2.558 mRNA cop-ies/18S rRNA unit, respectively) had a decreased mean survival time of 32 months for EpCAM and 42 months for both LGR5 and LGR4 at a 12‐year follow‐up (p = 0.022, p = 0.005 and p = 0.011, respec-tively). Additional patients at risk for recurrence were detected when LGR5 was combined with the biomarkers CXCL17 or CEA plus CXCL16. In conclusion, the study underscores LGR5 as a particularly useful prognostic biomarker and illustrates the strength of combining biomarkers detecting different subpopulations of cancer cells and/or cells in the tumor microenvironment for predicting recurrence.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CEA, Colon cancer, CXCL16, CXCL17, EpCAM, LGR4, LGR5, Prognosis, QRT‐PCR, Regional lymph nodes, Stem cell mark-ers
in
International Journal of Molecular Sciences
volume
23
issue
1
article number
403
publisher
MDPI AG
external identifiers
  • pmid:35008827
  • scopus:85121867889
ISSN
1661-6596
DOI
10.3390/ijms23010403
language
English
LU publication?
yes
id
84db1f17-26c0-4aa8-a4d6-34bbb57031cc
date added to LUP
2023-01-03 14:27:54
date last changed
2024-03-21 10:45:59
@article{84db1f17-26c0-4aa8-a4d6-34bbb57031cc,
  abstract     = {{<p>The significance of cancer stem cells (CSCs) in initiation and progression of colon cancer (CC) has been established. In this study, we investigated the utility of measuring mRNA expression levels of CSC markers EpCAM, LGR5 and LGR4 for predicting survival outcome in surgically treated CC patients. Expression levels were determined in 5 CC cell lines, 66 primary CC tumors and 382 regional lymph nodes of 121 CC patients. Prognostic relevance was determined using Kaplan‐Meier survival and Cox regression analyses. CC patients with lymph nodes expressing high levels of EpCAM, LGR5 or LGR4 (higher than a clinical cutoff of 0.07, 0.06 and 2.558 mRNA cop-ies/18S rRNA unit, respectively) had a decreased mean survival time of 32 months for EpCAM and 42 months for both LGR5 and LGR4 at a 12‐year follow‐up (p = 0.022, p = 0.005 and p = 0.011, respec-tively). Additional patients at risk for recurrence were detected when LGR5 was combined with the biomarkers CXCL17 or CEA plus CXCL16. In conclusion, the study underscores LGR5 as a particularly useful prognostic biomarker and illustrates the strength of combining biomarkers detecting different subpopulations of cancer cells and/or cells in the tumor microenvironment for predicting recurrence.</p>}},
  author       = {{Abdelmageed, Manar and Ismail, Hager Tarek H. and Olsson, Lina and Lindmark, Gudrun and Hammarström, Marie Louise and Hammarström, Sten and Sitohy, Basel}},
  issn         = {{1661-6596}},
  keywords     = {{CEA; Colon cancer; CXCL16; CXCL17; EpCAM; LGR4; LGR5; Prognosis; QRT‐PCR; Regional lymph nodes; Stem cell mark-ers}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Clinical significance of stem cell biomarkers epcam, lgr5 and lgr4 mrna levels in lymph nodes of colon cancer patients}},
  url          = {{http://dx.doi.org/10.3390/ijms23010403}},
  doi          = {{10.3390/ijms23010403}},
  volume       = {{23}},
  year         = {{2022}},
}