Phosphatase and tensin homolog (PTEN) expression on oncologic outcome in renal cell carcinoma: A systematic review and meta-analysis

Tang, Lu; Li, Xintao; Gao, Yu; Chen, Luyao; Gu, Liangyou; Chen, Jianwen; Lyu, Xiangjun; Zhang, Xu

doi:10.1371/journal.pone.0179437

Cited by 30 publications

(22 citation statements)

References 43 publications

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“…Clinical analysis showed that ccRCC patients with the PTEN mutation have a significantly poorer prognosis in survival and disease recurrence. All these results indicate the significance of the clinical practice of the PTEN mutation in ccRCC patients, consistent with some recent research (22, 23). The detection of tumor gene mutations has been applied to the clinic, which can help clinicians judge the prognosis of patients and effectively select better individualized treatment strategies.…”

Section: Discussionsupporting

confidence: 92%

Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma

et al. 2019

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It is well established that the PTEN (Phosphatase and Tensin Homolog) mutant is a frequently mutated gene found in clear cell renal cell carcinoma (ccRCC), making it a potential biomarker for individualized treatment opinions. Here, in the present study, we designed a method to evaluate the significance of the PTEN mutation in the prognosis and drug selection of ccRCC, determine the potential changing pathways and genes associated with the mechanisms. The most recent TCGA data shows that the PTEN mutation is found in 5% of ccRCC patients. In total, 2,569 genes were identified as DEGs. GO and KEGG analysis suggested that DEGs were significantly enriched in categories associated with cell division and multiple metabolic progressions. The top 10 genes, ranked by degree, were identified as hub genes from the protein–protein interaction network (PPI). What is more, patients with the PTEN mutation were associated with a worsened prognosis of ccRCC. Data from the GDSC database indicated that the selective AKT inhibitor, GSK690693, is a selective inhibitor for ccRCC with the PTEN mutation. Our findings have indicated that multiple genes and pathways may play a crucial role in PTEN mutation ccRCC, offering candidate targets and strategies for PTEN mutation ccRCC individualized treatment.

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Section: Discussionsupporting

confidence: 92%

Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma

et al. 2019

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“…Que et al have recently carried out a meta-analysis identifying PTEN loss as a prognostic factor for worse overall survival (OS) in patients affected with kidney cancer due its role in increasing aggressiveness and the progression of this type of tumor [78]. Tang et al have also shown a statistically significant association between low levels of PTEN and unfavorable disease-specific survival in patients with Renal Cell Carcinoma (RCC), a specific subtype of kidney cancer [79]. However, in this series PTEN expression did not correlate with other clinicopathological features such as Fuhrman grade, pathological type (Clear Cell (CC)RCC vs. other RCC types) or clinical stage, thus rendering PTEN a good prognostic, but not predictive, biomarker for kidney cancer [79].…”

Section: Pten As a Prognostic Biomarkermentioning

confidence: 99%

PTEN as a Prognostic/Predictive Biomarker in Cancer: An Unfulfilled Promise?

Bazzichetto

Cognetti

Pallocca

et al. 2019

Cancers

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Identifying putative biomarkers of clinical outcomes in cancer is crucial for successful enrichment, and for the selection of patients who are the most likely to benefit from a specific therapeutic approach. Indeed, current research in personalized cancer therapy focuses on the possibility of identifying biomarkers that predict prognosis, sensitivity or resistance to therapies. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor gene that regulates several crucial cell functions such as proliferation, survival, genomic stability and cell motility through both enzymatic and non-enzymatic activities and phosphatidylinositol 3-kinase (PI3K)-dependent and -independent mechanisms. Despite its undisputed role as a tumor suppressor, assessment of PTEN status in sporadic human tumors has yet to provide clinically robust prognostic, predictive or therapeutic information. This is possibly due to the exceptionally complex regulation of PTEN function, which involves genetic, transcriptional, post-transcriptional and post-translational events. This review shows a brief summary of the regulation and function of PTEN and discusses its controversial aspects as a prognostic/predictive biomarker.

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“…PTEN expression status has previously been investigated for its prognostic and predictive value in RCC with the conflicting findings (11)(12)(13). For the purpose of this report, in addition to NGS/FACETS analyses, PTEN status was assessed by IHC to determine expression levels semiquantitatively.…”

Section: Pten Ihcmentioning

confidence: 99%

PTEN Expression, Not Mutation Status in TSC1, TSC2, or mTOR, Correlates with the Outcome on Everolimus in Patients with Renal Cell Carcinoma Treated on the Randomized RECORD-3 Trial

Voss

Chen

Reising

et al. 2019

Clinical Cancer Research

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Purpose: Genomic alterations in key components of PI3K/ mTOR pathway have been proposed as candidate predictive markers for rapalog therapy in renal cell carcinoma (RCC). We tested this hypothesis in patients from a randomized phase II trial of everolimus versus sunitinib. Patients and Methods: Archival specimens collected at baseline were analyzed with targeted next-generation sequencing (NGS). Focus of interest were alterations in key PI3K pathway components. PTEN expression was assessed by IHC. Association between molecular findings and treatment outcomes was investigated; same associations were tested for 2 everolimus-treated trial cohorts in gastric and hepatocellular carcinoma (HCC). Results: Among 184 everolimus-treated patients with RCC with NGS data, mutation rates in genes of interest were 6% (TSC1), 4.4% (TSC2), and 8.2% (mTOR); 44% harbored alterations in !1 PI3K pathway component. For subjects with presence versus absence of mutations in TSC1, TSC2, or mTOR progression-free survival (PFS) neither differed on univariate analysis (HR, 1.0; P ¼ 0.895) nor on multivariate testing stratified by MSKCC risk group and other established prognostic factors (HR, 1.1; P ¼ 0.806). Everolimus-treated patients with retained (n ¼ 50) versus lost (n ¼ 50) PTEN IHC expression had median PFS of 5.3 months versus 10.5 months (HR, 2.5; P < 0.001). Such differences were not seen with sunitinib (10.9 months vs. 10.3 months; HR, 0.8; P ¼ 0.475). Molecular findings did not correlate with outcomes in gastric and HCC cohorts. Conclusions: Association between mutation status for TSC1/TSC2/mTOR and therapeutic outcome on everolimus was not confirmed. Clinically meaningful differences in PFS were seen based on PTEN expression by IHC, lost in >50% of patients.

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Phosphatase and tensin homolog (PTEN) expression on oncologic outcome in renal cell carcinoma: A systematic review and meta-analysis

Cited by 30 publications

References 43 publications

Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma

Significance of PTEN Mutation in Cellular Process, Prognosis, and Drug Selection in Clear Cell Renal Cell Carcinoma

PTEN as a Prognostic/Predictive Biomarker in Cancer: An Unfulfilled Promise?

PTEN Expression, Not Mutation Status in TSC1, TSC2, or mTOR, Correlates with the Outcome on Everolimus in Patients with Renal Cell Carcinoma Treated on the Randomized RECORD-3 Trial

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