Abstract
A tumor can be viewed as a special “organ” that undergoes aberrant and poorly regulated organogenesis. Progress in cancer prognosis and therapy might be facilitated by re-examining distinctive processes that operate during normal development, to elucidate the intrinsic features of cancer that are significantly obscured by its heterogeneity. The global gene expression signatures of 44 human lung tissues at four development stages from Asian descent and 69 lung adenocarcinoma (ADC) tissue samples from ethnic Chinese patients were profiled using microarrays. All of the genes were classified into 27 distinct groups based on their expression patterns (named as PTN1 to PTN27) during the developmental process. In lung ADC, genes whose expression levels decreased steadily during lung development (genes in PTN1) generally had their expression reactivated, while those with uniformly increasing expression levels (genes in PTN27) had their expression suppressed. The genes in PTN1 contain many n-gene signatures that are of prognostic value for lung ADC. The prognostic relevance of a 12-gene demonstrator for patient survival was characterized in five cohorts of healthy and ADC patients [ADC_CICAMS (n = 69, p = 0.007), ADC_PNAS (n = 125, p = 0.0063), ADC_GSE13213 (n = 117, p = 0.0027), ADC_GSE8894 (n = 62, p = 0.01), and ADC_NCI (n = 282, p = 0.045)] and in four groups of stage I patients [ADC_CICAMS (n = 22, p = 0.017), ADC_PNAS (n = 76, p = 0.018), ADC_GSE13213 (n = 79, p = 0.02), and ADC_qPCR (n = 62, p = 0.006)]. In conclusion, by comparison of gene expression profiles during human lung developmental process and lung ADC progression, we revealed that the genes with a uniformly decreasing expression pattern during lung development are of enormous prognostic value for lung ADC.
Highlights
Cancer is a major public health problem
With data from embryonic lung tissues, we identified a group of genes with a particular expression pattern during development as enriched with robust lung ADC prognostic information, which might be helpful for constructing prognosis prediction models and developing novel treatment approaches for this deadly disease
The gene expression profiles of human lung development were described in this study, a large amount of fundamental data are provided for future research, and gene expression patterns in conjunction with their underlying biological functions were analyzed
Summary
Cancer is a major public health problem. It is a leading cause of death and one in eight deaths worldwide is due to cancer [1]. A great challenge in the diagnosis and treatment of cancer arises from its ability to manifest with a great variety of pathologies and clinical behaviors due to its molecular heterogeneity. Global gene expression profiling has helped to dissect tumor heterogeneity, e.g., breast cancer was classified into four main subtypes according to microarray data [2], this heterogeneity remains a seemingly unconquerable barrier to eliminating the uncertainties of cancer cell behavior and is a major challenge in elucidating the mechanisms of oncogenesis [3]. Progress may be made by re-examining distinctive processes that operate during normal development [5] to elucidate the intrinsic features of cancer that are significantly obscured by its heterogeneity
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