Dataset Information

Identification of TNM stage-specific genes in lung adenocarcinoma by genome-wide expression profiling.

ABSTRACT: The present study aimed to investigate the molecular basis of lung cancer development using a microarray to identify the differentially-expressed genes associated with the various tumor-node-metastasis (TNM) stages of lung adenocarcinoma. This subtype of lung cancer has increased in incidence within recent years in China. A 35K oligo gene array covering ~25,100 genes was used to screen the differentially-expressed genes among 90 lung adenocarcinoma samples of various TNM stages. To verify the data from the gene arrays, three genes [human zinc finger-containing, Miz1, PIAS-like protein on chromosome 7 (Zimp7), GINS complex subunit 2 (GINS2) and NSAID activated gene 1 (NAG-1)] were validated using quantitative (q)PCR in an alternative set of samples to the gene array. A total of 640 genes were identified that were differentially-expressed in lung adenocarcinoma compared with the surrounding normal lung tissues. From these 640 candidate genes, 10 were observed to be differentially-expressed among TNM stages I, II and IIIA, of which, the Zimp7, GINS2 and NAG-1 genes were reported for the first time to be expressed at high levels in lung adenocarcinoma. The results of the qPCR for the three genes were consistent with those from the gene array. In total, 10 candidate genes were identified to be associated with the various TNM stages of lung adenocarcinoma in the population studied, which may provide new insights into the molecular basis underlying the development of lung adenocarcinoma and offer new targets for the diagnosis, therapy and prognosis.

SUBMITTER: Liu M

PROVIDER: S-EPMC3789070 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of TNM stage-specific genes in lung adenocarcinoma by genome-wide expression profiling.

Liu Ming M Pan Hong H Zhang Feng F Zhang Yongbiao Y Zhang Yang Y Xia Han H Zhu Jing J Fu Weiling W Zhang Xiaoli X

Oncology letters 20130715 3

The present study aimed to investigate the molecular basis of lung cancer development using a microarray to identify the differentially-expressed genes associated with the various tumor-node-metastasis (TNM) stages of lung adenocarcinoma. This subtype of lung cancer has increased in incidence within recent years in China. A 35K oligo gene array covering ~25,100 genes was used to screen the differentially-expressed genes among 90 lung adenocarcinoma samples of various TNM stages. To verify the da ...[more]

PMID: 24137407

Similar Datasets

Project description:UnlabelledKlebsiella pneumoniae is an urgent public health threat because of resistance to carbapenems, antibiotics of last resort against Gram-negative bacterial infections. Despite the fact that K. pneumoniae is a leading cause of pneumonia in hospitalized patients, the bacterial factors required to cause disease are poorly understood. Insertion site sequencing combines transposon mutagenesis with high-throughput sequencing to simultaneously screen thousands of insertion mutants for fitness defects during infection. Using the recently sequenced K. pneumoniae strain KPPR1 in a well-established mouse model of pneumonia, insertion site sequencing was performed on a pool of >25,000 transposon mutants. The relative fitness requirement of each gene was ranked based on the ratio of lung to inoculum read counts and concordance between insertions in the same gene. This analysis revealed over 300 mutants with at least a 2-fold fitness defect and 69 with defects ranging from 10- to >2,000-fold. Construction of 6 isogenic mutants for use in competitive infections with the wild type confirmed their requirement for lung fitness. Critical fitness genes included those for the synthesis of branched-chain and aromatic amino acids that are essential in mice and humans, the transcriptional elongation factor RfaH, and the copper efflux pump CopA. The majority of fitness genes were conserved among reference strains representative of diverse pathotypes. These results indicate that regulation of outer membrane components and synthesis of amino acids that are essential to its host are critical for K. pneumoniae fitness in the lung.ImportanceKlebsiella pneumoniae is a bacterium that commonly causes pneumonia in patients after they are admitted to the hospital. K. pneumoniae is becoming resistant to all available antibiotics, and when these infections spread to the bloodstream, over half of patients die. Since currently available antibiotics are failing, we must discover new ways to treat these infections. In this study, we asked what genes the bacterium needs to cause an infection, since the proteins encoded by these genes could be targets for new antibiotics. We identified over 300 genes that K. pneumoniae requires to grow in a mouse model of pneumonia. Many of the genes that we identified are found in K. pneumoniae isolates from throughout the world, including antibiotic-resistant forms. If new antibiotics could be made against the proteins that these genes encode, they may be broadly effective against K. pneumoniae.

Project description:RNA modifications implicate pathological and prognosis significance in cancer development and progression, of which, m6A and m5C are representative regulators. These RNA modifications could produce effects on the function of other RNA by regulating gene expression. Thus, in this study, we aimed to explore the correlation between m6A/m5C regulators and early-stage lung adenocarcinoma (LUAD). Only the early-stage LUAD samples were included in this investigation, and the RNA-seq dataset of The Cancer Genome Atlas (TCGA) cohort was utilized to evaluate the expression of 37 m6A/m5C regulated genes. Based on the expression level of these 37 genes, early-stage LUAD patients were divided into 2 clusters, which were performed by consensus clustering, and the m6A/m5C subtypes had significantly different prognostic outcomes (p < 0.001). Cluster1, which has a better prognosis, was characterized by the C3 (inflammatory) immune subtype, low immune infiltration, chemokine expression, major histocompatibility complex (MHC) expression, and immune checkpoint molecule expression. Furthermore, compared with cluster1, cluster2 showed a T cell exhaustion state, characterized by a high expression of immune checkpoint genes, and immune cells, such as T cells, CD8+ T cells, cytotoxic lymphocytes, NK cells, and so on. In addition, patients in cluster2 were with high tumor mutational burden (TMB) and numerous significant mutated oncogene and tumor suppressor genes, such as WNT10B, ERBB4, SMARCA4, TP53, and CDKN2A (p < 0.001). A total of 19 genes were mostly related to the prognosis of LUAD and were upregulated in cluster2 (p < 0.05), showing a positive correlation with the mRNA expression of 37 m6A/m5C regulated genes. The predictive risk model was constructed using Cox and LASSO (least absolute shrinkage and selection operator) regression analysis. Finally, a seven-gene m6A/m5C risk model, comprising of METTL3, NPLOC4, RBM15, YTHDF1, IGF2BP1, NSUN3, and NSUN7, was constructed to stratify the prognosis of early-stage LUAD (p = 0.0049, AUC = 0.791). The high-risk score was associated with a poorer prognosis. This model was also validated using two additional GEO datasets: GSE72094 (p = 0.011, AUC = 0.736) and GSE50081 (p = 0.012, AUC = 0.628). In summary, it was established that the m6A/m5C-regulated genes performed a crosstalk function in the mRNA expression of early-stage LUAD. By interacting with other mRNA genes, m6A/m5C modification disturbs DNA replication and the tumor immune microenvironment (TIME). The seven-gene risk model may be a critical tool for the prognostic assessment of early-stage LUAD.

Dataset Information

Identification of TNM stage-specific genes in lung adenocarcinoma by genome-wide expression profiling.

Publications

Identification of TNM stage-specific genes in lung adenocarcinoma by genome-wide expression profiling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets