Molecular characteristics of non-small cell lung cancer

Abstract

We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers. Separation of normal and tumor, as well as histopathological subtypes, was evident by using the 3,921 most abundant transcript tags. This distinction remained when only 115 highly differentially expressed tags were used. Furthermore, these 115 transcript tags clustered into groups suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, whereas squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21 WAF1/CIP1 and 14-3-3, were consistently underexpressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression patterns observed by SAGE were consistent with results obtained by quantitative real-time PCR or cDNA array analyses by using a total of 43 lung tumor and normal samples. Thus, although derived from only a few tissue libraries, gene expression profiles obtained by using SAGE most likely represent an unbiased yet distinctive molecular signature for the most common forms of human lung cancer.

Expression profiling of primary non-small cell lung cancer for target identification

“…Similarly, S100A2 has been reported to be overexpressed in ovarian cancer (Hough et al, 2001). However the gene lists are substantially different to those generated in other NSCLC studies (Garber et al, 2001;Bhattacharjee et al, 2001;Giordano et al, 2001;Nacht et al, 2001). This is likely due to the different criteria used to build the lists in response to different primary aims (classification versus target identification).…”

Role of cell‐cycle regulators in lung cancer

“…Moreover, we were able to identify Rb2/ p130 point mutations in primary lung cancer (Claudio et al, 2000) and to study the expression of pRb2/p130 target genes in a lung cancer cell line by microarray analysis (Russo et al, 2003). Today, several lung cancer microarray studies are available (Bhattacharjee et al, 2001;Garber et al, 2001;Goodwin et al, 2001;Nacht et al, 2001;Bangur et al, 2002;Beer et al, 2002;Chen et al, 2002Chen et al, , 2003Gordon et al, 2002;Heighway et al, 2002;Miura et al, 2002;Wigle et al, 2002;Kikuchi et al, 2003;Powell et al, 2003). By using a computerized approach, it is possible to analyze in detail the presence of differential gene expression profiles of RB, Rb2/p130, and p107 in lung cancer from these microarray data (Table 2).…”

Two subclasses of lung squamous cell carcinoma with different gene expression profiles and prognosis identified by hierarchical clustering and non-negative matrix factorization

“…This latter provides a direct method of surveying gene transcription and has increased our understanding of several cancers including lung carcinomas (Bhattacharjee et al, 2001;Garber et al, 2001;Nacht et al, 2001;Miura et al, 2002;Virtanen et al, 2002;Borczuk et al, 2003;Amatschek et al, 2004;Jones et al, 2004;Kettunen et al, 2004;Tomida et al, 2004). Here, we used microarray-based expression profiling techniques to subclassify a series of lung SCCs.…”