Evaluation of Prognostic-Significance of P53 Gene Alterations in Patients With Surgically Resected Lung-Cancer

Kashii, Tatsuhiko; Mizushima, Yutaka; Lima, Carlos; Noto, Hirofumi; Sato, Hikari; Saito, Haruhiro; Kusajima, Yoshinori; Kitagawa, Masanobu; Sugiyama, S.; Kobayashi, M

doi:10.3892/ijo.6.1.123

Cited by 3 publications

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“…In the study of Ludovini et al (37), 55% of the patients with NSCLC possessed TP53 mutations, and the incidence of the mutations was higher in squamous-cell carcinomas and in smokers compared with those in adenocarcinomas and non-smokers, as previously reported by Fong et al (42). In the studies of Fukuyama et al (16) and Kashii et al (29), it was stated that TP53 mutations were an unfavorable prognostic factor in patients with adenocarcinoma, although not in patients with squamous cell carcinoma (SCC), in spite of its higher frequency (16,29), a conclusion which has been borne out by the results in the present study. On further analysis, the tumors with wild-type TP53 more often had a K-ras mutation (P=0.036), which is known to constitute an unfavorable prognostic factor in lung adenocarcinoma.…”

Section: Discussionsupporting

confidence: 54%

TP53 mutation is associated with a poor clinical outcome for non-small cell lung cancer: Evidence from a meta-analysis

Zhou

Huang

et al. 2016

Molecular and Clinical Oncology

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A number of studies have examined the association between tumor protein 53 (TP53) mutations and the clinical outcome in patients with non-small-cell lung cancer (NSCLC), although these have yielded conflicting results. In the present study, electronic databases updated to September 2015 were searched to find relevant studies. A meta-analysis was performed on the eligible studies, which quantitatively evaluated the association between the TP53 mutations and the survival of patients with NSCLC. Subgroup and sensitivity analyses were performed. A total of 19 studies that involved a total of 6,084 patients with NSCLC were included. When the TP53 mutation group (n=1,406) was compared with the wild-type group (lacking TP53 mutations; n=1,965), the wild-type group was associated with a significantly higher overall survival rate [hazard ratio (HR), 1.26; 95% confidence interval (CI) 1.12–1.41, P<0.0001]. Significant benefits of overall survival in the wild-type group were found in the subgroup involving patients with NSCLC in the early stages, including the I/II phases (HR, 1.93, 95% CI, 1.17–3.19, P=0.01; heterogeneity, I2=0.0%, P=0.976) and patients with adenocarcinoma (HR, 3.06; 95% CI, 1.66–5.62, P<0.0001; heterogeneity: I2=0.0%, P=0.976). This meta-analysis has indicated that TP53 gene alteration may be an indicator of a poor prognosis in patients with NSCLC. Furthermore, the results also suggested that the role of TP53 mutations may differ according to different pathological types and clinical stages. The presence of these mutations may define a subset of patients with NSCLC appropriate for investigational therapeutic strategies.

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Section: Discussionsupporting

confidence: 54%

TP53 mutation is associated with a poor clinical outcome for non-small cell lung cancer: Evidence from a meta-analysis

Zhou

Huang

et al. 2016

Molecular and Clinical Oncology

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“…The same results were reported in other studies. 52 , 53 Molina-Vila et al 54 were the only to apply Poeta et al classification 36 in a cohort of advanced-stage non-small-cell lung cancer; only nondisruptive mutations were associated with a shorter survival. Our results cannot be compared, since we included only patients with squamous cell carcinoma, and our cohort consisted of only 80/438 patients with advanced stage (III–IV); because of these promising results, we included all patients in a whole cohort, including patients with head and neck-, oesophageal- and lung squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer

et al. 2020

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Background Mutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC). However, it is not yet clear whether specific TP53 mutations bear distinct clinical and pathophysiological significance in different HNSCC subgroups. Methods A systematic bioinformatics appraisal of TP53 mutations was performed on 415 HNSCC cases available on The Cancer Genome Atlas (TCGA). The following features were analysed and correlated with known clinicopathological variables: mutational profile of TP53, location (within secondary structure and predicted domains of p53 protein) and well-known hotspot mutations. Interactome–genome–transcriptome network analysis highlighted different gene networks. An algorithm was generated to develop a new prognostic classification system based on patients’ overall survival. Results TP53 mutations in HNSCCs exhibited distinct differences in different anatomical sites. The mutational profile of TP53 was an independent prognostic factor in HNSCC. High risk of death mutations, identified by our novel classification algorithm, was an independent prognostic factor in TCGA HNSCC database. Finally, network analysis suggested that distinct p53 molecular pathways exist in a site- and mutation-specific manner. Conclusions The mutational profile of TP53 may serve as an independent prognostic factor in HNSCC patients, and is associated with distinctive site-specific biological networks.

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Association Between Gene Alteration and Drug-Sensitivity in Human Lung-Carcinoma Cell-Lines

Mizushima¹,

Kashii²,

Kobayashi³

1995

Oncol Rep

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Evaluation of Prognostic-Significance of P53 Gene Alterations in Patients With Surgically Resected Lung-Cancer

Cited by 3 publications

References 0 publications

TP53 mutation is associated with a poor clinical outcome for non-small cell lung cancer: Evidence from a meta-analysis

TP53 mutation is associated with a poor clinical outcome for non-small cell lung cancer: Evidence from a meta-analysis

Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer

Association Between Gene Alteration and Drug-Sensitivity in Human Lung-Carcinoma Cell-Lines

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