Ari Pelli1,2, Juha P Väyrynen1,2, Kai Klintrup3,4, Jyrki Mäkelä3,4, Markus J Mäkinen1,2, Anne Tuomisto1,2, Tuomo J Karttunen5,6. 1. Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland. 2. Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland. 3. Research Unit of Surgery, Anesthesia and Intensive Care, University of Oulu, Oulu, Finland. 4. Department of Surgery, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland. 5. Department of Pathology, Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland. tuomo.karttunen@oulu.fi. 6. Department of Pathology, Oulu University Hospital and Medical Research Center Oulu, Oulu, Finland. tuomo.karttunen@oulu.fi.
Abstract
AIMS: Gremlin1 is a bone morphogenetic protein (BMP) antagonist with a suggested role in colorectal cancer (CRC) progression. We have analysed Gremlin1 protein expression in CRC and assessed its correlation with clinicopathological characteristics, including developmental pathway and prognosis. METHODS AND RESULTS: Material included a non-selected series of 148 surgically treated CRC cases. The tumour-node-metastasis (TNM) stage, histological grade and inflammatory infiltrate at the invasive margin were assessed, and tumours were classified to serrated or non-serrated types. Immunohistochemistry was conducted to evaluate Gremlin1 expression. Prognosis (60-month follow-up) was analysed by Kaplan-Meier methods and Cox regression analysis. Gremlin1 expression was detected in epithelial cells both in normal mucosa and in carcinomas. Abundant expression in carcinomas associated with low TNM stage (P = 0.044), low histological grade (P = 0.044), serrated histology (P = 0.033 or P = 0.053 depending on the classification cut-off) and intensive inflammatory infiltrate at the invasive margin (P = 0.044), and was a stage independent indicator of extended survival (P = 0.029). CONCLUSIONS: Gremlin1 protein expression in CRC associates with low tumour stage and extended survival independently of tumour stage, suggesting that it represents a relevant prognostic indicator in CRC. High expression in carcinomas with serrated histology suggests a potential role for Gremlin1 in the serrated pathway of CRC.
AIMS: Gremlin1 is a bone morphogenetic protein (BMP) antagonist with a suggested role in colorectal cancer (CRC) progression. We have analysed Gremlin1 protein expression in CRC and assessed its correlation with clinicopathological characteristics, including developmental pathway and prognosis. METHODS AND RESULTS: Material included a non-selected series of 148 surgically treated CRC cases. The tumour-node-metastasis (TNM) stage, histological grade and inflammatory infiltrate at the invasive margin were assessed, and tumours were classified to serrated or non-serrated types. Immunohistochemistry was conducted to evaluate Gremlin1 expression. Prognosis (60-month follow-up) was analysed by Kaplan-Meier methods and Cox regression analysis. Gremlin1 expression was detected in epithelial cells both in normal mucosa and in carcinomas. Abundant expression in carcinomas associated with low TNM stage (P = 0.044), low histological grade (P = 0.044), serrated histology (P = 0.033 or P = 0.053 depending on the classification cut-off) and intensive inflammatory infiltrate at the invasive margin (P = 0.044), and was a stage independent indicator of extended survival (P = 0.029). CONCLUSIONS:Gremlin1 protein expression in CRC associates with low tumour stage and extended survival independently of tumour stage, suggesting that it represents a relevant prognostic indicator in CRC. High expression in carcinomas with serrated histology suggests a potential role for Gremlin1 in the serrated pathway of CRC.
Authors: Elena A Pudova; Anna V Kudryavtseva; Maria S Fedorova; Andrew R Zaretsky; Dmitry S Shcherbo; Elena N Lukyanova; Anatoly Y Popov; Asiya F Sadritdinova; Ivan S Abramov; Sergey L Kharitonov; George S Krasnov; Kseniya M Klimina; Nadezhda V Koroban; Nadezhda N Volchenko; Kirill M Nyushko; Nataliya V Melnikova; Maria A Chernichenko; Dmitry V Sidorov; Boris Y Alekseev; Marina V Kiseleva; Andrey D Kaprin; Alexey A Dmitriev; Anastasiya V Snezhkina Journal: BMC Genomics Date: 2018-02-09 Impact factor: 3.969