Article Abstract

Fibroblast growth factor 7 signalling is disrupted in colorectal cancer and is a potential marker of field cancerisation

Authors: Abhilasha Patel, Gyanendra Tripathi, Philip McTernan, Kishore Gopalakrishnan, Omar Ali, Emma Spector, Nigel Williams, Ramesh P. Arasaradnam

Abstract

Background: Field cancerisation proposes that there are pre-malignant genetic mutations in the macroscopically normal mucosa (MNM) tissue around colorectal cancer. To evaluate fibroblast growth factor 7 (FGF7) tissue expression in the mucosal field around colorectal cancer.
Methods: Gene and protein expression of FGF7, its receptor, FGFR2 and its downstream targets; FRS2α, Erk 1/2 and Akt was measured from mucosal samples in 34 control subjects and 17 cancer patients. Serial samples from tumour, adjacent to tumour and at the resection margin were utilised.
Results: FGF7 gene expression was significantly higher in tumour (2.3 fold), adjacent mucosa (3.2 fold) and resection margin (2.8 fold) of cancer patients compared with control subjects (P<0.01 respectively). However, FGFR2 was down regulated (3.5 fold) in the tumour tissue (P<0.001). Protein expression of FRS2α and Akt was significantly lower in tumour tissue compared with the resection margin in cancer patients (P<0.05 respectively). No differences in protein expression of Erk 1/2 were detected.
Conclusions: FGF7 was elevated in the mucosal field of cancer patients supporting its potential as a biomarker of field cancerisation. Changes in FRS2α, Akt and Erk 1/2 expression in the tumour tissue indicate that with malignant transformation, FGF7 loses its ability to regulate cellular differentiation.

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