Lung tumor cells: A multivariate approach to cell classification using two‐dimensional protein pattern

Abstract

High resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a powerful research tool for the analytical separation of cellular proteins. The qualitative and quantitative pattern of polypeptides synthesized by a cell represents its phenotype and thus defines characteristics such as the morphology and the biological behavior of the cell. By analyzing and comparing the protein patterns of different cells it is possible to recognize the cell type and also to identify the most typical features of these cells. In applied pathology it is often difficult to identify the tissue of origin and the stage or grade of a neoplasia by cellular morphology analyzed by classical or immunostaining procedures. The protein pattern itself is the most characteristic feature of a cell and should therefore contribute to the identification of the cell type. For this reason we separated protein fractions originating from different lung tumor cell lines using 2-D PAGE and we compared the resulting patterns on a multivariate statistical level using correspondence analysis (CA) and ascendant hierarchical clustering (AHC). The results indicate that (i) protein patterns are highly typical for cells and that (ii) the comparison of the protein patterns of a set of interesting cell types allows the identification of potentially new marker proteins. 2-D PAGE is thus a unique and powerful tool for molecular cytology or histopathology, unveiling the protein expression level of tissues or cells.

The Human Plasma Proteome

“…Quantitative serum protein proteomics was used to show that a panel of high abundance acute phase-related proteins could give a better statistical measure of inflammation than the classical marker serum amyloid A (41). Cancer tissue samples could be analyzed to distinguish tumor type and prognosis (146), and a panel of six cancer markers in plasma was found to be useful (147,148). More recently, mass spectrometry-based proteomic approaches have been used as well to discover patterns of diseaserelated protein features related to a specific cancer (65).…”

A database of protein expression in lung cancer

“…Specific protein differences between different types of cancer have been identified by other groups. In a recent study of breast, ovary and lung tumors, 20 differentially expressed proteins were identified [9] and in a prior study, 16 polypeptides were found to be associated with different histopathological features of lung cancer [10,11]. In a study of 25 adenocarcinomas of the lung, 12 small cell lung cancers, and 16 squamous cell tumors, by our group (manuscript submitted) an initial analysis of protein 2-D patterns uncovered a group of 52 protein spots that differed in average integrated intensity between the three groups.…”

Identification of procaryotic developmental stages by statistical analyses of two‐dimensional gel patterns

“…Two-dimensional (2-D) gels offer the potential of defining developmental stages by their global pattern of gene expression. The possibility of using statistical methods to classify 2-D gel profiles has been used by Anderson et al [l] and Schmid et al [2] for comparative studies of different cell cultures. The first description of multivariate methods for the detection of progressive changes in a series of 2-D gel electrophoretic patterns was reported by our laboratories in a study of the heat shock response in a procaryotic bacteria, Streptomyces coelicolor [3].…”