STAGE SPECIFIC PROTEIN MARKERS IN COLON CARCINOMA

鉴于科洛的偶数亚群的多效性生长特征， 直肠肿瘤细胞似乎怀疑是否有任何单一的分子标记物 可以作为预后指标。 是 然而，可以想象，一组分子，其中每一个都可以 个别缺乏预测价值，可以形成一个独特的定量 关于结肠直肠癌进展的信息模式 肿瘤 最近，一个基于计算机的，高分辨率，定量的两个- 双向凝胶电泳系统（QUEST系统）已被用于 在几种大鼠细胞中解析并定量2000多种细胞蛋白 这样的定义的蛋白质组，其定量表达变化 在不同的生长条件下， 这项技术 似乎非常适合记录个体的数量差异， 结肠直肠肿瘤表达的蛋白质。 提出了一 通过QUEST系统对精心选择的结肠癌进行表征 细胞系将提供一个蛋白质数据库， 在不同细胞系中定量表达的蛋白质 对应于限定的肿瘤阶段将允许识别集合 候选标记蛋白。 这些蛋白质的特征在于 分子量、pI、糖基化、膜整合和亚细胞 本地化 如果不是全部的话，这些蛋白质中的一些将被分子克隆 在筛选程序中使用QUEST系统， 并且肽抗血清将被制备，使得克隆的 可以在结肠直肠肿瘤活组织检查中评估蛋白质。 结直肠肿瘤细胞的生长特性明显 受多种因素控制。 可以想象，其中一个 这是免疫系统的作用。 最近的观察表明， I型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， 这些抗原的测量在化疗中可能具有预测价值 结肠直肠肿瘤 I类MHC抗原的诱导表达似乎 涉及非多态性基因，其功能未知，但其 结构表明，基因产物可能是一些靶结构， 细胞毒性T淋巴细胞亚群。 建议寡核苷酸和 对单个非多态性I类抗原特异的抗体探针 应该准备好，并且使用这种探针的预测价值 应评估结直肠肿瘤活检的冰冻切片。

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.