Department of Gastroenterology, University Hospitals Coventry and Warwickshire, Clifford Bridge Road, Coventry CV2 2DX, UK.
Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Int J Mol Sci. 2021 Feb 28;22(5):2430. doi: 10.3390/ijms22052430.
The impact of tumour associated stroma on cancer metastasis is an emerging field. However, cancer associated genes in peritumoral adipose tissue (pAT) in human colon cancer have not been explored. The aim of this study was to identify differentially expressed genes (DEGs) associated with cancer pathways in mesenteric pAT compared with adjacent adipose tissue. In total, nine patients with colon cancer pathological stage T2/T4 were employed in this study. DEGs were identified in 6 patients employing Nanostring PanCancer Pathway Panel and pathway enrichment analyses were performed. Differential expression of the 5 most up-regulated and 2 down regulated genes was validated with qRT-PCR. Results showed collagen type I alpha 1 chain () = 0.007; secreted frizzled related protein () = 0.057; fibroblast growth factor 7 () not significant (ns); phospholipase A2, group IIA () ns; nerve growth factor receptor () ns; lymphoid enhancer binding factor 1 () = 0.03; cadherin 1, Type 1, E-cadherin (epithelial) () 0.09. Results have highlighted down-regulation of the Wingless/Integrated (Wnt) pathway in mesenteric pAT compared to distal adipose tissue. Highly upregulated genes in mesenteric pAT were involved in extracellular matrix (ECM)-receptor interactions and focal adhesion. Highly down regulated genes were involved in the cell cycle. Immunohistochemistry revealed differential distribution of COL1A1 showing maximum levels in tumour tissue and gradually decreasing in distant adipose tissue. and down regulation of Wnt pathway may have a role in local invasion and distant metastasis. may represent a stromal prognostic biomarker and therapeutic target in colon cancer.
肿瘤相关基质对癌症转移的影响是一个新兴领域。然而，人类结肠癌瘤周脂肪组织（pAT）中的癌症相关基因尚未被探索。本研究的目的是鉴定与结直肠系膜 pAT 中癌症通路相关的差异表达基因（DEGs），并与相邻脂肪组织进行比较。本研究共纳入 9 名病理分期为 T2/T4 的结肠癌患者。采用 Nanostring PanCancer 通路面板鉴定了 6 名患者的 DEGs，并进行了通路富集分析。通过 qRT-PCR 验证了 5 个上调基因和 2 个下调基因的差异表达。结果显示，I 型胶原α 1 链（）=0.007；分泌卷曲相关蛋白（）=0.057；成纤维细胞生长因子 7（）不显著（ns）；磷脂酶 A2，组 IIA（）ns；神经生长因子受体（）ns；淋巴增强结合因子 1（）=0.03；钙黏蛋白 1，I 型，E-钙黏蛋白（上皮）（）0.09。结果表明，与远端脂肪组织相比，肠系膜 pAT 中的 Wnt 通路下调。肠系膜 pAT 中高度上调的基因参与细胞外基质（ECM）-受体相互作用和焦点黏附。高度下调的基因参与细胞周期。免疫组化显示 COL1A1 的分布存在差异，在肿瘤组织中表达水平最高，在远处脂肪组织中逐渐降低。Wnt 通路的下调可能在局部浸润和远处转移中发挥作用。可能代表结直肠癌的一种基质预后生物标志物和治疗靶点。
