Prognostic Factors in Resected Stage I Non–Small-Cell Lung Cancer: A Multivariate Analysis of Six Molecular Markers

Lu, Charles; Soria, Jean Charles; Tang, Ximing; Xu, Xiao Chun; Luo, Wei; Li, Mao; Lotan, Reuben; Kemp, Bonnie L.; Bekele, B. Nebiyou; Feng, Lei; Hong, Waun Ki; Khuri, Fadlo R.

doi:10.1200/jco.2004.01.091

Cited by 136 publications

(108 citation statements)

References 48 publications

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“…In lung cancers, DAPk promoter methylation was associated with aggressive disease and poor survival. [35][36][37][38] Lung tumors that were positive for DAPk hypermethylation showed advanced pathological stage, larger tumor size and lymph node involvement. 35 Similarly, DAPk hypermethylation in head and neck cancer correlated with lymph node involvement and advanced disease stage.…”

Section: Dapk Family and Cancer: A Novel Tumor Suppressor Family Of Pmentioning

confidence: 99%

DAPk Protein Family and Cancer

Gözüaçık¹,

Kimchi²

2006

Autophagy

191

172

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The Death-Associated Protein kinase (DAPk) family contains three closely related serine/threonine kinases, named DAPk, ZIPk and DRP-1, which display a high degree of homology in their catalytic domains. The recent discovery of protein-protein interactions and kinase/substrate relationships among these family members suggests that the three kinases may form multi-protein complexes capable of transmitting apoptotic or autophagic cell death signals in response to various cellular stresses including the misregulated expression of oncogenes in premalignant cells. Several lines of evidence indicate that the most studied member of the family, DAPk, has tumor and metastasis suppressor properties. Here we present an overview of the data connecting the DAPk family of proteins to cell death and malignant transformation and discuss the possible involvement of the autophagic cell death-inducing capacity of DAPk in its tumor suppressor activity.

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Section: Dapk Family and Cancer: A Novel Tumor Suppressor Family Of Pmentioning

confidence: 99%

DAPk Protein Family and Cancer

Gözüaçık¹,

Kimchi²

2006

Autophagy

191

172

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“…There is considerable evidence of elevated COX-2 levels in NSCLC, and this is of importance in lung carcinogenesis [9][10][11]. It was published that higher levels of COX-2 are more related to ADC than to SCC [12][13][14][15], and over-expression of COX-2 has been proposed as a biomarker for biologically aggressive types of NSCLC and poorer survival [16][17][18]. The correlation between the higher expression of COX-2 and hTERT in NSCLC was already discussed and proposed as a prognostic marker [18].…”

Section: Introductionmentioning

confidence: 99%

“…It was published that higher levels of COX-2 are more related to ADC than to SCC [12][13][14][15], and over-expression of COX-2 has been proposed as a biomarker for biologically aggressive types of NSCLC and poorer survival [16][17][18]. The correlation between the higher expression of COX-2 and hTERT in NSCLC was already discussed and proposed as a prognostic marker [18]. The MDM2 oncogene, mostly over-expressed in NSCLC, is the main negative regulator of p53 [19][20][21].…”

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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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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“…We found one significant interaction between COX-2 and stage (Po0.01). When we aggregated the six studies (Achiwa et al, 1999;Khuri et al, 2001;Araki et al, 2004;Lu et al, 2004;Richardson et al, 2005;Yuan et al, 2005) giving separate results about stage I NSCLC, the combined HR was statistically significant by using the random-effect model: HR 1.64, 95% CI (1.21 -2.24) as there was indeed a significant heterogeneity (P ¼ 0.04) (Figure 2). We did not observe a statistically significant effect of COX-2 on survival in ADC (five evaluable studies) (Achiwa et al, 1999;Araki et al, 2004;Yamaguchi et al, 2004;Richardson et al, 2005;Yuan et al, 2005) with HR 1.35 (95% CI 0.62 -2.95) (random effect; test of heterogeneity Po0.001).…”

Section: Meta-analysismentioning

confidence: 98%

“…Fourteen publications, published between 1999 and 2005, were eligible for the systematic review (Achiwa et al, 1999;Hosomi et al, 2000;Khuri et al, 2001;Brabender et al, 2002;Kim et al, 2003;Ab' Saber et al, 2004;Araki et al, 2004;Lu et al, 2004;Yamaguchi et al, 2004;Brattstrom et al, 2005;Laga et al, 2005;Marrogi et al, 2005;Richardson et al, 2005;Yuan et al, 2005). These publications concerned different cohorts of patients.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

et al. 2006

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Cyclooxygenase-2 (COX-2) is overexpressed in lung cancer, especially in adenocarcinoma (ADC). Our aim was to determine the prognostic value of COX-2 on survival in patients with lung cancer. Studies evaluating the survival impact of COX-2 in lung cancer, published until December 2005, were selected. Data for estimation of individual hazard ratios (HR) for survival were extracted from the publications and combined in a pooled HR. Among 14 eligible papers, all dealing with non-small-cell lung cancer, 10 provided results for meta-analysis of survival data (evaluable studies). Cyclooxygenase-2 positivity was associated with reduced survival, improved survival or no statistically significant impact in six, one and seven studies, respectively. Combined HR for the 10 evaluable studies (1236 patients) was 1.39 (95% confidence intervals (CI): 0.97 -1.99). In stage I lung cancer (six evaluable studies, 554 patients), it was 1.64 (95% CI: 1.21 -2.24). No significant impact was shown in ADC. A slight detrimental effect on survival in patients with lung cancer is associated with COX-2 expression, but the statistical significance is not reached. This effect is statistically significant in stage I, suggesting that COX-2 expression could be useful at early stages to distinguish those with a worse prognosis.

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Prognostic Factors in Resected Stage I Non–Small-Cell Lung Cancer: A Multivariate Analysis of Six Molecular Markers

Abstract: In this cohort of resected stage I NSCLC patients, molecular markers that independently predict cancer-specific survival have been identified. The prognostic roles of DAPK methylation, IL-10, and other biomarkers in NSCLC merit further investigation.

Cited by 136 publications

References 48 publications

DAPk Protein Family and Cancer

DAPk Protein Family and Cancer

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

Has Cox-2 a prognostic role in non-small-cell lung cancer? A systematic review of the literature with meta-analysis of the survival results

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