MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer

Ko, Jiunn‐Liang; Cheng, Ya Wen; Shu, Chang; Su, Jen Ming; Chen, Chih Yi; Lee, Huei

doi:10.1002/1097-0215(20000520)89:3<265::aid-ijc9>3.0.co;2-n

Cited by 59 publications

(37 citation statements)

References 23 publications

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“…Most expression analysis is still done at the protein level via imunohistochemical assays, so discrepancies in the results for the researched genes can be a consequence not just of different NSCLC types or different pathways of tumourigenesis, but also of the different techniques used for gene expression analysis and the different interpretations of the results. We proved that COX-2 and hTERT are already over-expressed at the mRNA level and that higher expression levels are related to NSCLC tumours, as already stated [17,18,27,28]. We also confirmed that COX-2 gene expression was significantly higher in ADC, as was already known [12][13][14][15].…”

Section: Discussionsupporting

confidence: 88%

“…Downregulation of MDM2 expression has also been found in primary lung tumours, mostly in SCC, and is related to an alternative pathway to NSCLC pathogenesis [27]. MDM2 mRNA expression was determined as a favourable prognostic factor in NSCLC [28]. LATS2 has a role in cell cycle regulation, the maintenance of mitotic fidelity and genomic stability, and the promotion of apoptosis through the downregulation of the anti-apoptotic proteins of the Bcl family [29][30][31][32].…”

Section: Introductionmentioning

confidence: 99%

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The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

Stražišar

Mlakar

Glavač

2009

Cellular and Molecular Biology Letters

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Abbreviations used: ADC -adenocarcinoma; CDK2 -cyclin-dependent kinase 2; cDNAcomplementary DNA; COX-2 -cyclooxygenase 2; C T -cycle threshold; DNAdeoxyribonucleic acid; GAPDH -glyceraldehyde-3-phosphate dehydrogenase; hTERThuman telomerase reverse transcriptase; IHC -immunohistochemistry; LATS2 -homolog of large tumour suppressor 2, Drosophilae; LCC -large cell carcinoma; MDM2 -mouse double minute 2 homolog; mRNA -messenger RNA; NSCLC -non-small cell lung cancer; p21 -cyclin-dependent kinase inhibitor 1A; p53 -tumour protein p53; PCR -polymerase chain reaction; pTNM -pathological tumour-node-metastasis; RB -retinoblastoma; RNAribonucleic acid; r s -Spearman's rank correlation coefficient; RT-PCR -real time PCR; S100A2 -S100 calcium binding protein A2; SCC -squamous cell carcinoma , we analysed the expression of the COX-2, hTERT, MDM2, LATS2 and S100A2 genes and researched the relationships between the NSCLC types and the differences in expression levels. The differences in the expression levels of the LATS2, S100A2 and hTERT genes in different types of NSCLC are significant. hTERT and COX-2 were over-expressed and LATS2 under-expressed in all NSCLC. We also detected significant relative differences in the expression of LATS2 and MDM2, hTERT and MDM2 in different types of NSCLC. There was a significant difference in the average expression levels in S100A2 for ADC and SCC. Our study shows differences in the expression patterns within the NSCLC group, which may mimic the expression of the individual NSCLC type, and also new relationships in the expression levels for different NSCLC types.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

Stražišar

Mlakar

Glavač

2009

Cellular and Molecular Biology Letters

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“…Most authors have analyzed earlystage, surgically resected tumors where sufficient tissue is available for mutational testing by standard techniques. When TP53 mutations were uncategorized, some studies found no association with outcome (29) or only identified a trend, which was lost in the multivariate analysis (30). Other studies observed an association between TP53 mutations and response to adjuvant therapy (31) or with shorter OS, either alone (32; only in stage I disease) or in combination with other molecular markers (33).…”

Section: Discussionmentioning

confidence: 99%

“…Nondisruptive mutations could be more frequent in smokers whose tumors develop a high genetic instability (29) and other, as yet unknown, genetic alterations may be responsible for the worse outcomes. This would make our findings spurious, positioning nondisruptive TP53 mutations as a bystander of those alterations.…”

Section: Discussionmentioning

confidence: 99%

Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Molina-Vila

Bertrán-Alamillo

Gasco

et al. 2014

Clinical Cancer Research

138

149

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Purpose: TP53 mutations in early-stage non-small cell lung cancer (NSCLC) may be associated with worse survival but their prognostic role in advanced NSCLC is controversial. In addition, it remains unclear whether mutated patients represent a clinically homogeneous group.Experimental Design: We retrospectively examined TP53 mutations and outcome in a training cohort of 318 patients with stage IIIB-IV NSCLC: 125 epidermal growth factor receptor (EGFR) wild-type (wt) and 193 EGFR mutated (mut). An independent validation cohort of 64 EGFR-mut patients was subsequently analyzed. Mutations were classified as "disruptive" and "nondisruptive" according to their predicted degree of disturbance of the p53 protein structure and function.Results: In the training cohort, TP53 mutations were found in 43 of the 125 EGFR-wt patients (34.4%). Of these, 28 had nondisruptive TP53 mutations and a median overall survival (OS) of 8.5 months, compared with 15.6 months for the remaining 97 patients (P ¼ 0.003). In the EGFR-mut group, TP53 mutations were found in 50 of the 193 patients (25.9%). The OS for the 26 patients with TP53 nondisruptive mutations was 17.8 months versus 28.4 months for the remaining 167 patients (P ¼ 0.04). In the validation cohort, the 11 patients with nondisruptive TP53 mutations had a median OS of 18.1 months compared with 37.8 months for the 53 remaining patients (P ¼ 0.006). In multivariate analyses, nondisruptive TP53 mutations had an independent, significant association with a shorter OS.Conclusions: Nondisruptive mutations in the TP53 gene are an independent prognostic factor of shorter survival in advanced NSCLC.

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“…Molecules with frequent activating alterations in lung cancers are marked in red. Molecules showing frequent and infrequent inactivations are indicated in dark and light blue, respectively association with a favorable prognosis (Higashiyama et al, 1997;Ko et al, 2000). p14ARF, which is encoded by an alternative coding frame of the p16INK4A locus, exerts growth inhibition by inhibiting the ubiquitin E3 ligase activity of MDM2 (Honda and Yasuda, 1999) and by sequestering MDM2 into the nucleolus (Weber et al, 1999;Zhang and Xiong, 1999).…”

Section: Tumor Suppressors and Growth Inhibitory Signalsmentioning

confidence: 99%

Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer

2002

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MDM2 mRNA expression is a favorable prognostic factor in non-small-cell lung cancer

Cited by 59 publications

References 23 publications

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

Nondisruptive p53 Mutations Are Associated with Shorter Survival in Patients with Advanced Non–Small Cell Lung Cancer

Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer

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