Patel Abhilasha, Tripathi Gyanendra, McTernan Philip, Gopalakrishnan Kishore, Ali Omar, Spector Emma, Williams Nigel, Arasaradnam Ramesh P
Department of Colorectal Surgery, University Hospitals of Coventry and Warwickshire NHS Trust, Coventry, UK.
Warwick Medical School, University of Warwick, Coventry, UK.
J Gastrointest Oncol. 2019 Jun;10(3):429-436. doi: 10.21037/jgo.2019.02.11.
Field cancerisation proposes that there are pre-malignant genetic mutations in the macroscopically normal mucosal tissue around colorectal cancer. This study aims to evaluate fibroblast growth factor 7 (FGF7) tissue expression in the mucosal field around colorectal cancer.
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.
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.
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.
场癌化假说认为，在结直肠癌周围宏观上正常的黏膜组织中存在癌前基因突变。本研究旨在评估成纤维细胞生长因子7（FGF7）在结直肠癌周围黏膜场中的组织表达情况。
检测了34名对照受试者和17名癌症患者黏膜样本中FGF7及其受体FGFR2以及其下游靶点FRS2α、Erk 1/2和Akt的基因和蛋白表达。使用了来自肿瘤、肿瘤旁以及切缘的系列样本。
与对照受试者相比，癌症患者的肿瘤组织（2.3倍）、肿瘤旁黏膜（3.2倍）和切缘组织（2.8倍）中FGF7基因表达显著更高（P值均<0.01）。然而，FGFR2在肿瘤组织中下调（3.5倍）（P<0.001）。癌症患者肿瘤组织中FRS2α和Akt的蛋白表达与切缘相比显著更低（P值分别<0.05）。未检测到Erk 1/2蛋白表达的差异。
FGF7在癌症患者的黏膜场中升高，支持其作为场癌化生物标志物的潜力。肿瘤组织中FRS2α、Akt和Erk 1/2表达的变化表明，随着恶性转化，FGF7失去了调节细胞分化的能力。
