Department of General Surgery, The Affiliated Zhongshan Hospital of Xiamen University, The Digestive Disease Research Institute of Xiamen University, Xiamen 361004, Fujian Province, China.
World J Gastroenterol. 2010 Mar 7;16(9):1129-37. doi: 10.3748/wjg.v16.i9.1129.
To investigate the diverse characteristics of different pathological gradings of gastric adenocarcinoma (GA) using tumor-related genes.
GA tissues in different pathological gradings and normal tissues were subjected to tissue arrays. Expressions of 15 major tumor-related genes were detected by RNA in situ hybridization along with 3' terminal digoxin-labeled anti-sense single stranded oligonucleotide and locked nucleic acid modifying probe within the tissue array. The data obtained were processed by support vector machines by four different feature selection methods to discover the respective critical gene/gene subsets contributing to the GA activities of different pathological gradings.
In comparison of poorly differentiated GA with normal tissues, tumor-related gene TP53 plays a key role, although other six tumor-related genes could also achieve the Area Under Curve (AUC) of the receiver operating characteristic independently by more than 80%. Comparing the well differentiated GA with normal tissues, we found that 11 tumor-related genes could independently obtain the AUC by more than 80%, but only the gene subsets, TP53, RB and PTEN, play a key role. Only the gene subsets, Bcl10, UVRAG, APC, Beclin1, NM23, PTEN and RB could distinguish between the poorly differentiated and well differentiated GA. None of a single gene could obtain a valid distinction.
Different from the traditional point of view, the well differentiated cancer tissues have more alterations of important tumor-related genes than the poorly differentiated cancer tissues.
利用肿瘤相关基因探讨不同病理分级胃腺癌(GA)的特征差异。
采用组织芯片技术检测不同病理分级 GA 组织及正常组织中 15 种主要肿瘤相关基因的表达,采用 RNA 原位杂交技术,用组织芯片内 3' 末端 digoxin 标记的反义单链寡核苷酸和锁核酸修饰探针检测这些基因的表达。采用支持向量机(SVM)和 4 种不同的特征选择方法对数据进行处理,以发现导致不同病理分级 GA 活性的关键基因/基因子集。
与正常组织相比,低分化 GA 组织中肿瘤相关基因 TP53 发挥关键作用,尽管其他 6 个肿瘤相关基因也可以通过更多的特征选择方法独立获得大于 80%的曲线下面积(AUC)。与正常组织相比,高分化 GA 组织中 11 个肿瘤相关基因也可以通过更多的特征选择方法独立获得大于 80%的 AUC,但只有基因子集 TP53、RB 和 PTEN 发挥关键作用。只有基因子集 Bcl10、UVRAG、APC、Beclin1、NM23、PTEN 和 RB 能够区分低分化和高分化 GA。没有一个单一基因能够获得有效的区分。
与传统观点不同,高分化癌组织中重要肿瘤相关基因的改变比低分化癌组织更多。