The prognostic value of leucine-rich repeat-containing G-protein (Lgr5) and its impact on clinicopathological features o
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ORIGINAL ARTICLE – CANCER RESEARCH
The prognostic value of leucine‑rich repeat‑containing G‑protein (Lgr5) and its impact on clinicopathological features of colorectal cancer Arkadiusz Gzil1,2 · Izabela Zarębska1,2 · Damian Jaworski1,2 · Paulina Antosik1,2 · Justyna Durślewicz1,2 · Joanna Maciejewska1,2 · Ewa Domanowska1,2 · Natalia Skoczylas‑Makowska1,2 · Navid Ahmadi4 · Dariusz Grzanka1,2 · Łukasz Szylberg1,2,3,5 Received: 9 April 2020 / Accepted: 6 July 2020 © The Author(s) 2020
Abstract Introduction Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world. Recent research suggests that cancer stem cells (CSCs) are responsible for tumor cell’s malignant behavior in CRC. This study has been designed to determinate clinical implications of CSC markers: CD44, DCLK1, Lgr5, and ANXA2 in CRC. Materials and methods The study was performed on tissue samples which were collected from 89 patients undergoing colectomy. Formalin-fixed paraffin-embedded tissue blocks with representative tumor areas were identified and corded. Immunohistochemical staining was performed using anti-CD44, anti-LGR5, anti-ANXA2, and anti-DCLK1 antibodies. The H-score system was utilized to determine the immunointensity of CRC cells. Results The lower expression of Lgr5 was significantly correlated with the presence of lymph-node metastases (p = 0.011), while high expression of Lgr5 was statistically significant in vascular invasion in examined cancer tissue samples (p = 0.027). Moreover, a high H-score value of Lgr5 expression was significantly related to a reduced overall survival rate (p = 0.043). Conclusion Our results suggest a strong relationship between CSC marker Lgr5 and vascular invasion, presence of lymphnode metastasis, and overall poor survival. The presence of Lgr5 might be an unfavorable prognostic factor, and its high level in cancer tissue is related to an aggressive course. This marker could also be used to access the effectiveness of the treatment. Keywords Lgr5 · DCLK1 · ANAX2 · CD44 · CSC · Colorectal cancer
Introduction
* Arkadiusz Gzil [email protected] 1
Department of Clinical Pathomorphology, Collegium Medicum in Bydgoszcz, Sklodowskiej‑Curie Str. 9, 85‑094 Bydgoszcz, Poland
2
Nicolaus Copernicus University, Toruń, Poland
3
Department of Pathomorphology, Military Clinical Hospital, Bydgoszcz, Poland
4
Chair and Department of Oncologic Pathology and Prophylactics, Greater Poland Cancer Center, Poznan University of Medical Sciences, Poznan, Poland
5
Department of Tumor Pathology and Pathomorphology, Oncology Center, Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland
Colorectal cancer (CRC) constitutes one of the most prevalent malignancies in the world, contributing 9% of the total number of new cases diagnosed in 2018 in the United States (Siegel et al. 2019). Factors associated with an increased risk or development of CRC include obesity, physical inactivity, smoking, alcohol use, age, type 2 diabetes mellitus, and a family history
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