Dataset Information

Identification of novel deregulated RNA metabolism-related genes in non-small cell lung cancer.

ABSTRACT: Lung cancer is a leading cause of cancer death worldwide. Several alterations in RNA metabolism have been found in lung cancer cells; this suggests that RNA metabolism-related molecules are involved in the development of this pathology. In this study, we searched for RNA metabolism-related genes that exhibit different expression levels between normal and tumor lung tissues. We identified eight genes differentially expressed in lung adenocarcinoma microarray datasets. Of these, seven were up-regulated whereas one was down-regulated. Interestingly, most of these genes had not previously been associated with lung cancer. These genes play diverse roles in mRNA metabolism: three are associated with the spliceosome (ASCL3L1, SNRPB and SNRPE), whereas others participate in RNA-related processes such as translation (MARS and MRPL3), mRNA stability (PCBPC1), mRNA transport (RAE), or mRNA editing (ADAR2, also known as ADARB1). Moreover, we found a high incidence of loss of heterozygosity at chromosome 21q22.3, where the ADAR2 locus is located, in NSCLC cell lines and primary tissues, suggesting that the downregulation of ADAR2 in lung cancer is associated with specific genetic losses. Finally, in a series of adenocarcinoma patients, the expression of five of the deregulated genes (ADAR2, MARS, RAE, SNRPB and SNRPE) correlated with prognosis. Taken together, these results support the hypothesis that changes in RNA metabolism are involved in the pathogenesis of lung cancer, and identify new potential targets for the treatment of this disease.

SUBMITTER: Valles I

PROVIDER: S-EPMC3410905 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Identification of novel deregulated RNA metabolism-related genes in non-small cell lung cancer.

Valles Iñaki I Pajares Maria J MJ Segura Victor V Guruceaga Elisabet E Gomez-Roman Javier J Blanco David D Tamura Akiko A Montuenga Luis M LM Pio Ruben R

PloS one 20120802 8

Lung cancer is a leading cause of cancer death worldwide. Several alterations in RNA metabolism have been found in lung cancer cells; this suggests that RNA metabolism-related molecules are involved in the development of this pathology. In this study, we searched for RNA metabolism-related genes that exhibit different expression levels between normal and tumor lung tissues. We identified eight genes differentially expressed in lung adenocarcinoma microarray datasets. Of these, seven were up-regu ...[more]

PMID: 22876301

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Project description:Background: Studies have reported that RNA-binding proteins (RBPs) are dysregulated in multiple cancers and are correlated with the progression and prognosis of disease. However, the functions of RBPs in non-small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the function of RBPs in NSCLC and their prognostic and therapeutic value. Methods: The mRNA expression profiles, DNA methylation data, gene mutation data, copy number variation data, and corresponding clinical information on NSCLC were downloaded from The Cancer Genome Atlas, Gene Expression Omnibus, and the University of California Santa Cruz Xena databases. The differentially expressed RBPs were identified between tumor and control tissues, and the expression and prognostic value of these RBPs were systemically investigated by bioinformatics analysis. A quantitative polymerase chain reaction (qPCR) was performed to validate the dysregulated genes in the prognostic signature. Results: A prognostic RBP-related signature was successfully constructed based on eight RBPs represented as a risk score using least absolute shrinkage and selection operator (LASSO) regression analysis. The high-risk group had a worse overall survival (OS) probability than the low-risk group (p < 0.001) with 1-, 3-, and 5-year area under the receiver operator characteristic curve values of 0.671, 0.638, and 0.637, respectively. The risk score was associated with the stage of disease (p < 0.05) and was an independent prognostic factor for NSCLC when adjusted for age and UICC stage (p < 0.001, hazard ratio (HR): 1.888). The constructed nomogram showed a good predictive value. The P53, focal adhesion, and NOD-like receptor signaling pathways were the primary pathways in the high-risk group (adjusted p value <0.05). The high-risk group was correlated with increased immune infiltration (p < 0.05), upregulated relative expression levels of programmed cell death 1 (PD1) (p = 0.015), cytotoxic T-lymphocyte-associated protein 4 (CTLA4) (p = 0.042), higher gene mutation frequency, higher tumor mutational burden (p = 0.034), and better chemotherapy response (p < 0.001). The signature was successfully validated using the GSE26939, GSE31210, GSE30219, and GSE157009 datasets. Dysregulation of these genes in patients with NSCLC was confirmed using the qPCR in an independent cohort (p < 0.05). Conclusion: An RBP-related signature was successfully constructed to predict prognosis in NSCLC, functioning as a reference for individualized therapy, including immunotherapy and chemotherapy.

Dataset Information

Identification of novel deregulated RNA metabolism-related genes in non-small cell lung cancer.

Publications

Identification of novel deregulated RNA metabolism-related genes in non-small cell lung cancer.

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