STAGE SPECIFIC PROTEIN MARKERS IN COLON CARCINOMA

考虑到COLO-R偶数子集的多向性生长特征。 直肠肿瘤细胞是否有单一的分子标志物似乎值得怀疑 可以确定可以作为预后指标。它是 然而，可以想象，一组分子，其中每一个都可以 个体缺乏预测性价值，可以形成鲜明的量化 关于结直肠癌进展的信息丰富的模式 肿瘤。最近，一种基于计算机的、高分辨率的、定量的两个- 空间凝胶电泳仪(QUEST系统)已被用于 在几个大鼠细胞中分解和定量2000多种细胞蛋白 数量表达不同的已定义的蛋白质集合 在不同的生长条件下已经确定。这项技术 似乎非常适合记录个体之间的数量差异 结直肠肿瘤表达的蛋白质。现建议将一项 QUEST系统对精心选择的结肠癌的定性研究 细胞系将提供一个由2000多个蛋白质组成的数据库 蛋白质，其在不同细胞系中的定量表达 与定义的肿瘤分期相对应将允许识别集合 候选标记蛋白。这些蛋白质的特征是 分子量、等电点、糖基化、膜整合和亚细胞 本地化。这些蛋白质中的一部分，如果不是全部的话，将被分子克隆 QUEST系统在筛选程序和寡核苷酸探针中的应用 并将制备的多肽抗血清用于克隆的表达 蛋白质可以在结直肠癌活检组织中进行评估。 结直肠癌细胞生长特征明显 受多种因素控制。可以想象的是，其中一个 因素是免疫系统的作用。最近观察到的那个班级 主要组织相容性复合体(MHC)抗原在多种 DNA损伤剂处理后的细胞数量表明 这些抗原的测定可能对化疗有预测价值。 结直肠肿瘤。诱导表达的I类MHC抗原似乎 涉及非多态基因，其功能未知，但其 结构提示基因产物可能是某些基因的靶结构。 细胞毒性T淋巴细胞亚群。有人建议，寡核苷酸和 针对单个、非多态的I类抗原的抗体探针 应该准备好，并且这种探头用于 结直肠癌活检的冰冻切片应该进行评估。

In view of the pleiotropic growth characteristics of even subsets of colo- rectal tumor cells it seems doubtful whether any single molecular markers can be identified that may serve as prognostic indicators. It is conceivable, however, that a set of molecules, each one of which may individually lack predictive value, can form a distinctive quantitative pattern that is informative with regard to the progression of a colo-rectal tumor. Recently, a computer-based, high resolution, quantitative two- dimensional gel electrophoresis system (the QUEST system) has been used to resolve and quantitate more than 2000 cellular proteins in several rat cell lines such that defined sets of proteins whose quantitative expression vary under different growth conditions have been identified. This technology seems eminently well suited to record quantitative differences in individual proteins expressed by colo-rectal tumors. It is proposed that a characterization by the QUEST system of carefully selected colon carcinoma cell lines will provide a protein database consisting of well over 2000 proteins, whose quantitative expression in different cell lines corresponding to defined tumor stages will allow the identification of sets of candidate marker proteins. Such proteins will be characterized as to molecular weight, pI, glycosylation, membrane integration and subcellular localization. Some if not all of these proteins will be molecularly cloned using the QUEST system in the screening procedure and oligonucleotide probes and peptide antisera will be prepared such that the expression of the cloned proteins can be assessed in colo-rectal tumor biopsies. The growth characteristics of colo-rectal tumor cells are obviously controlled by a variety of factors. It is conceivable that one of these factors is the role of the immune system. The recent observation that class I major histocompatibility complex (MHC) antigens are induced in a variety of cells following treatment with DNA damaging agents suggests that measurements of such antigens may be of predictive value in the chemotherapy of colo-rectal tumors. The induced expression of class I MHC antigens seems to involve the non-polymorphic genes, whose function is unknown but whose structure suggests that the gene products may be target structures for some subset of cytotoxic T lymphocytes. It is proposed that oligonucleotide and antibody probes specific for individual, non-polymorphic class I antigens should be prepared and that the predictive value of such probes used on frozen sections of colo-rectal tumor biopsies should be evaluated.