Expression profiles of metastatic brain tumor from lung adenocarcinomas on cDNA microarray

Abstract

Abstract. Distant metastasis is one of the crucial parameters determining the type of treatment and prognosis of patients. Previous studies discovered important factors involved in multiple steps of metastasis, the precise mechanisms of metastasis still remain to be clarified. To identify genes associated with this complicated biological feature of cancer, we analyzed expression profiles of 16 metastatic brain tumors derived from primary lung adenocarcinoma (ADC) using cDNA microarray representing 23,040 genes. We applied bioinformatic algorithm to compare the expression data of these 16 brain metastatic loci with those of 37 primary NSCLCs including 22 ADCs, and found that metastatic tumor cells has very different characteristics of gene expression patterns from primary ones. Two hundred and forty-four genes that showed significantly different expression levels between the two groups included plasma membrane bounding proteins, cellular antigens, and cytoskeletal proteins that might play important roles in altering cell-cell communication, attachment, and cell motility, and enhance the metastatic ability of cancer cells. Our results provide valuable information for development of predictive markers as well as novel therapeutic target molecules for metastatic brain tumor of ADC of the lung. IntroductionDistant metastasis is one of crucial steps in tumor development and progression causing difficulty in treatment and resulting in patient death (1,2). Since there is no curative therapy for metastatic tumors at present, novel strategies for diagnosis at an earlier stage and better therapies to improve patient survival with metastatic cancer are urgently required. Distant metastasis is considered to occur as multiple-step events which include invasion from a primary site, penetration into blood or lymphatic flow, circulation to reach distant organs, extravasation into a target organ, and re-growth (3,4). To clarify this complicated but clinically important metastatic process, many investigators have attempted to identify the molecules of importance in these steps, but precise mechanisms of metastasis still remain largely unknown (5-7).Because microarray technology allows us to analyze expression level of thousands of genes simultaneously, we previously applied this technology to characterize nonsmall cell lung carcinomas (NSCLCs), which include adenocarcinoma (ADC) and squamous cell carcinoma (SCC), and indicated that biological characteristics of each lung cancer like the risk of lymph node metastasis could be predictable by the expression profile of the tumor cells (8). In addition to the lymph node metastasis, lung cancer is known to show higher rate of brain metastasis; nearly 30% of metastatic brain tumors are derived from primary lung cancer. Lung ADC is generally characterized by the early development of brain metastasis, that is observed even in some cases whose primary tumor is symptom-free (9). The incidence of brain metastasis, based on autopsy findings, is as high as 50% in patients with ADC (10,11). Few ...

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