LGR6 is a prognostic biomarker for less differentiated tumors in lymph nodes of colon cancer patients

Hagar Eltorky; Manar AbdelMageed; Hager Ismail; Faten Zahran; Adel Guirgis; Lina Olsson; Gudrun Lindmark; Marie-Louise Hammarström; Sten Hammarström; Basel Sitohy

doi:10.3389/fonc.2024.1393075

LGR6 is a prognostic biomarker for less differentiated tumors in lymph nodes of colon cancer patients

Front Oncol. 2024 Apr 23:14:1393075. doi: 10.3389/fonc.2024.1393075. eCollection 2024.

Authors

Hagar Eltorky^{1

2

3}, Manar AbdelMageed^{1

2

4}, Hager Ismail^{1

2

5}, Faten Zahran³, Adel Guirgis⁶, Lina Olsson¹, Gudrun Lindmark⁷, Marie-Louise Hammarström¹, Sten Hammarström¹, Basel Sitohy^{1

2}

Affiliations

¹ Department of Clinical Microbiology, Umeå University, Umeå, Sweden.
² Department of Diagnostics and Intervention, Umeå University, Umeå, Sweden.
³ Department of Biochemistry, Faculty of Science, Zagazig University, Zagazig, Egypt.
⁴ Department of Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁵ Department of Clinical Pathology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt.
⁶ Department of Molecular Biology, Genetic Engineering, and Biotechnology Research Institute, University of Sadat City, Sadat, Menoufia, Egypt.
⁷ Institution of Clinical Sciences, Lund University, Lund, Sweden.

Abstract

Introduction: The aim was to investigate whether the stem cell marker LGR6 has prognostic value in colon cancer, alone or in combination with the prognostic biomarkers CEA and CXCL16.

Methods: LGR6 mRNA levels were determined in 370 half lymph nodes of 121 colon cancer patients. Ability to predict relapse after curative surgery was estimated by Kaplan-Meier survival model and Cox regression analyses.

Results: Patients with high LGR6 levels [LGR6(+)] had a decreased mean survival time of 11 months at 5-year follow-up and 47 months at 12-year follow-up, respectively, with hazard ratios of 3.2 and 2.8. LGR6 mRNA analysis added prognostic value to CEA and CXCL16 mRNA analysis. In the poor prognosis groups CEA(+) and CXCL16(+), further division was achieved by LGR6 analysis. LGR6(+) patients had a very poor prognosis. LGR6 also identified a small number of CEA(-), TNM stage I patients who relapsed suggesting stem cell origin of these tumors. LGR6 and LGR5 levels correlated strongly in lymph nodes of stage I and IV patients but not in stage II patients, suggesting that these stem cell markers are differentially regulated.

Conclusion: This study highlights LGR6 as a useful prognostic biomarker independently and in combination with CEA, CXCL16 or LGR5 identifying different risk groups.

Keywords: CEA; CXCL16; LGR5; LGR6; cancer stem cells; colon cancer; qRT-PCR; regional lymph nodes.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by grants from the Swedish Research Council-Medicine and Health (BS) Grant number: 2008-7042, and Swedish Research Council-Natural and Engineering Sciences (M-LH) Grant number: 2010-05669 and 2013-04522, the Medical Faculty of Umeå University (BS and M-LH), the County Council of Västerbotten (BS) RV-995803, Kempe Foundation (BS), Grant number: JCK22-0003 and the Lions Cancer Research Fund (BS), Grant number: LP 24-2373, and Stig and Ragna Gorthon Foundation (GL).