Huang Chao, Liu Hong, Gong Xiuli, Wen Bin, Chen Dan, Liu Jinyuan, Hu Fengliang
Spleen‑Stomach Institute, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510000, P.R. China.
Pathology Department, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510000, P.R. China.
Mol Med Rep. 2016 Sep;14(3):2555-65. doi: 10.3892/mmr.2016.5584. Epub 2016 Aug 1.
The present study aimed to observe the varying expression of biomarkers in the microenvironment adjacent to colorectal cancer lesions to provide additional insight into the functions of microenvironment components in carcinogenesis and present a novel or improved indicator for early diagnosis of cancer. A total of 144 human samples from three different locations in 48 patients were collected, these locations were 10, 5 and 2 cm from the colorectal cancer lesion, respectively. The biomarkers analyzed included E‑cadherin, cytokeratin 18 (CK18), hyaluronidase‑1 (Hyal‑1), collagen type I (Col‑I), Crumbs3 (CRB3), vimentin, proteinase activated receptor 3 (PAR‑3), α‑smooth muscle actin (α‑SMA), cyclin D1 (CD1) and cluster of differentiation (CD)133. In addition, crypt architecture was observed. Related functional analysis of proteins was performed using hierarchical index cluster analysis. More severe destroyed crypt architecture closer to the cancer lesions was observed compared with the 10 cm sites, with certain crypts degraded entirely. Expression levels of E‑cadherin, CK18, CRB3 and PAR‑3 were lower in 2 cm sites compared with the 10 cm sites (all P<0.001), while the expression levels of the other biomarkers in the 2 cm sites were increased compared with 10 cm sites (all P<0.0001). Notably, the expression of CK18 in 2 cm sites was higher than in the 5 cm site (P<0.0001), which was different from the expression of E‑cadherin, CRB3 and PAR‑3. The expression levels of Hyal‑1 and Col‑I at the 2 cm sites were lower than that of the 5 cm sites (P>0.05 and P=0.0001, respectively), while the expression of vimentin, α‑SMA, CD1 and CD133 were not. Hyal‑1 and Col‑I may be independently important in cancer initiation in the tumor microenvironment. The results of the present study suggest that the biomarkers in the tissue microenvironment are associated with early tumorigenesis and may contribute to the development of carcinomas. These observations may be useful for early diagnosis of colorectal cancer.
本研究旨在观察结直肠癌病变周围微环境中生物标志物的表达变化,以进一步了解微环境成分在致癌过程中的作用,并为癌症早期诊断提供新的或改进的指标。共收集了48例患者三个不同位置的144份人体样本,这些位置分别距离结直肠癌病变10厘米、5厘米和2厘米。分析的生物标志物包括E-钙黏蛋白、细胞角蛋白18(CK18)、透明质酸酶-1(Hyal-1)、I型胶原(Col-I)、Crumbs3(CRB3)、波形蛋白、蛋白酶激活受体3(PAR-3)、α-平滑肌肌动蛋白(α-SMA)、细胞周期蛋白D1(CD1)和分化簇(CD)133。此外,还观察了隐窝结构。使用层次索引聚类分析对蛋白质进行相关功能分析。与距离癌症病变10厘米处相比,在距离癌症病变更近的位置观察到隐窝结构破坏更严重,部分隐窝完全降解。与10厘米处相比,2厘米处的E-钙黏蛋白、CK18、CRB3和PAR-3表达水平较低(均P<0.001),而2厘米处其他生物标志物的表达水平与10厘米处相比有所升高(均P<0.0001)。值得注意的是,2厘米处CK18的表达高于5厘米处(P<0.0001),这与E-钙黏蛋白、CRB3和PAR-3的表达情况不同。2厘米处Hyal-1和Col-I的表达水平低于5厘米处(分别为P>0.05和P=0.0001),而波形蛋白、α-SMA、CD1和CD133的表达则不然。Hyal-1和Col-I在肿瘤微环境中的癌症起始过程中可能各自具有重要意义。本研究结果表明,组织微环境中的生物标志物与肿瘤早期发生相关,可能有助于癌症的发展。这些观察结果可能对结直肠癌的早期诊断有用。