Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: adenocarcinoma and squamous cell carcinoma

Liu, J.; Yang, Xianghong; Shi, Weihong

doi:10.4238/2014.january.8.8

Cited by 33 publications

(29 citation statements)

References 25 publications

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“…Using gene expression profiling techniques, prior studies also demonstrated that adenocarcinoma and squamous cell NSCLCs have different expression portfolios (2,14), which is in line with our observation that the association between TP53 mutations and increased VEGF-A transcripts appears specific for adenocarcinoma of the lung. It is conceivable that the improved outcome that was previously reported by our group (5) in bevacizumab-treated patients who harbored TP53 mutations versus wild-type TP53 is due to the association between TP53 mutations and higher VEGF-A, the target for bevacizumab.…”

Section: Resultssupporting

confidence: 77%

VEGF-A Expression Correlates with TP53 Mutations in Non–Small Cell Lung Cancer: Implications for Antiangiogenesis Therapy

Schwaederlé¹,

Lazar

Validire³

et al. 2015

Cancer Research

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Bevacizumab is one of the most widely used antiangiogenic drugs in oncology, but the overall beneficial effects of this VEGF-A targeting agent are relatively modest, in part due to the lack of a biomarker to select patients most likely to respond favorably. Several molecular aberrations in cancer influence angiogenesis, including mutations in the tumor suppressor gene TP53, which occur frequently in many human malignancies. In this study, we present a multiple regression analysis of transcriptomic data in 123 patients with non-small cell lung cancer (NSCLC) showing that TP53 mutations are associated with higher VEGF-A expression (P ¼ 0.006). This association was interesting given a recent retrospective study showing longer progression-free survival in patients with diverse tumors who receive bevacizumab, if tumors harbor mutant TP53 instead of wild-type TP53. Thus, our current findings linking TP53 mutation with VEGF-A upregulation offered a mechanistic explanation for why patients exhibit improved outcomes after bevacizumab treatment when their tumors harbor mutant TP53 versus wild-type TP53. Overall, this work warrants further evaluation of TP53 as a ready biomarker to predict bevacizumab response in NSCLC and possibly other tumor types. Cancer Res; 75(7);

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Section: Resultssupporting

confidence: 77%

VEGF-A Expression Correlates with TP53 Mutations in Non–Small Cell Lung Cancer: Implications for Antiangiogenesis Therapy

Schwaederlé¹,

Lazar

Validire³

et al. 2015

Cancer Research

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“…We noted that the significant enriched pathways found in Table 6 (late-stage) are also identified in the work by Liu et al [76]. Except oocyte meiosis, the other four pathways are involved in two NSCLC subtypes: adenocarcinoma and squamous cell carcinoma.…”

Section: Resultssupporting

confidence: 72%

Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

Huang

Chang

Lin

et al. 2014

BioMed Research International

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Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC) is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.

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“…In a more recent study, Liu and colleagues [38] defined a set of differentially expressed genes and 16 pathways for AC and SCC. The most significant genes participated in the following pathways: cell cycle ( GSK3B , ATR , SKP2 , CDK1 , CDK2 , SMC3 , PLK1 , CCND3 ), DNA replication ( RFC2 , PRIM2 , MCM4 , MCM5 ), spliceosome ( PRPF19 , SRSF2 , THOC4 ), p53 signaling ( CDK1 , CDK2 , GTSE1 , ATR ), adherent junction ( IGF1R , TGFBR2 , CTNND1 ), and tight junction ( CKD4 , CASK , MPP5 ).…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Signature Differentiates Histology But Not Progression Status of Early-Stage NSCLC

Charkiewicz

Nikliński

Claesen

et al. 2017

Translational Oncology

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Advances in molecular analyses based on high-throughput technologies can contribute to a more accurate classification of non–small cell lung cancer (NSCLC), as well as a better prediction of both the disease course and the efficacy of targeted therapies. Here we set out to analyze whether global gene expression profiling performed in a group of early-stage NSCLC patients can contribute to classifying tumor subtypes and predicting the disease prognosis. Gene expression profiling was performed with the use of the microarray technology in a training set of 108 NSCLC samples. Subsequently, the recorded findings were validated further in an independent cohort of 44 samples. We demonstrated that the specific gene patterns differed significantly between lung adenocarcinoma (AC) and squamous cell lung carcinoma (SCC) samples. Furthermore, we developed and validated a novel 53-gene signature distinguishing SCC from AC with 93% accuracy. Evaluation of the classifier performance in the validation set showed that our predictor classified the AC patients with 100% sensitivity and 88% specificity. We revealed that gene expression patterns observed in the early stages of NSCLC may help elucidate the histological distinctions of tumors through identification of different gene-mediated biological processes involved in the pathogenesis of histologically distinct tumors. However, we showed here that the gene expression profiles did not provide additional value in predicting the progression status of the early-stage NSCLC. Nevertheless, the gene expression signature analysis enabled us to perform a reliable subclassification of NSCLC tumors, and it can therefore become a useful diagnostic tool for a more accurate selection of patients for targeted therapies.

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Identifying differentially expressed genes and pathways in two types of non-small cell lung cancer: adenocarcinoma and squamous cell carcinoma

Cited by 33 publications

References 25 publications

VEGF-A Expression Correlates with TP53 Mutations in Non–Small Cell Lung Cancer: Implications for Antiangiogenesis Therapy

VEGF-A Expression Correlates with TP53 Mutations in Non–Small Cell Lung Cancer: Implications for Antiangiogenesis Therapy

Drug Repositioning Discovery for Early- and Late-Stage Non-Small-Cell Lung Cancer

Gene Expression Signature Differentiates Histology But Not Progression Status of Early-Stage NSCLC

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