Integration and Analysis of CPTAC Proteomics Data in the Context of Cancer Genomics in the cBioPortal

Wu, Pamela; Heins, Zachary J.; Muller, James; Katsnelson, Lizabeth; Bruijn, Ino de; Abeshouse, Adam; Schultz, Nikolaus; Fenyö, David; Gao, Jianjiong

doi:10.1074/mcp.tir119.001673

Cited by 138 publications

(118 citation statements)

References 21 publications

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“…Gao C. et al. showed by measuring the levels of GSK-3β, PTEN, and AKT in breast tumor cell lines, that the PTEN/PI3K/AKT pathway can be regulated by GSK3 ( 58 ). PTEN inactivation is associated with lower survival and resistance to systemic treatment ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series

Alves

Borges²,

Kimberly

et al. 2021

Front. Oncol.

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BackgroundGlycogen Synthase Kinase-3 beta (GSK-3β) regulates diverse cell functions including metabolic activity, signaling and structural proteins. GSK-3β phosphorylates target pro-oncogenes and regulates programmed cell death-ligand 1 (PD-L1). This study investigated the correlation between GSK-3β expression and clinically relevant molecular features of lung adenocarcinoma (PDL1 score, PTEN expression and driver mutations).MethodsWe evaluated 95 lung cancer specimens from biopsies and surgical resections. Immunohistochemistry was performed to analyze the expression of GSK-3β, PTEN, and PDL1. Epidemiological data, molecular characteristics and staging were evaluated from medical records. The histologic classification was performed by an experienced pulmonary pathologist.ResultsMost patients were female (52.6%) and the majority had a positive smoking history. The median age was 68.3 years, with individuals over 60 years accounting for 82.1%. The predominant histological subtype was adenocarcinoma (69.5%), followed by squamous cell carcinoma (20.0%). GSK-3β expression in tumors was cytoplasmic with a dotted pattern and perinuclear concentration, with associated membranous staining. Seven (7.3%) tumors had associated nuclear expression localization. Seventy-seven patients (81.1%) had advanced clinical-stage tumors. GSK-3β was positive in 75 tumors (78%) and GSK3-positive tumors tended to be diagnosed at advanced stages. Among stage III/IV tumors, 84% showed GSK3 positivity (p= 0.007). We identified a statistically significant association between GSK-3β and PTEN in the qualitative analysis (p 0.021); and when comparing PTEN to GSK-3β intensity 2+ (p 0.001) or 3+ expression (> 50%) – p 0.013. GSK-3β positive tumors with a high histological score had a worse overall survival.ConclusionWe identified the histological patterns of GSK-3β expression and evaluated its potential as marker for overall survival, establishing a simple histological score to measure the evaluated status in resected tissues. The use of GSK-3β expression as an immune response biomarker remains a challenge. Future studies will seek to explain the role of its interaction with PTEN.

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Section: Discussionmentioning

confidence: 99%

Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series

Alves

Borges²,

Kimberly

et al. 2021

Front. Oncol.

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“…cBioPortal 2 is a user-friendly, comprehensive website resource and provides visualization, analysis, and download of large-scale cancer genomics datasets ( Wu et al, 2019 ). In our study, we analyzed the genetic alterations of TRiC, which contained genomic profiles counted on mutations and putative copy-number alterations (CNA) from GISTIC.…”

Section: Methodsmentioning

confidence: 99%

Systematic Characterization of Expression Profiles and Prognostic Values of the Eight Subunits of the Chaperonin TRiC in Breast Cancer

Song

Jiang

et al. 2021

Front. Genet.

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BackgroundChaperonin-containing TCP-1 (TRiC or CCT) was demonstrated to be involved in oncogenesis of cancers carcinogenesis and development of various malignancies. Increasing experimental evidence indicated that dysregulation of TRiC was implicated in the tumor progression of breast cancer (BCa). However, few definitive studies have addressed the diverse expression patterns and prognostic values of eight TRiC subunits. Thus, we aimed to investigate the clinical significance of TRiC subunit expression and prognostic values for their possible implications in diagnosis and treatment of BCa.MethodsBased on updated public resources and comprehensive bioinformatics analysis, we used some online databases (e.g., UALCAN, GEPIA, cBioPortal, TIMER, BC-GenExMiner, metascape, and GeneMANIA) to comprehensively explore the expression levels and the prognostic effects of eight TRiC subunits in patients with BCa.ResultsThe transcriptional levels of most subunits of the Chaperonin TRiC (CCT2, CCT3, CCT4, CCT5, CCT6A, and CCT7) were significantly elevated compared with normal breast tissues, whereas TCP1, CCT4, and CCT6B were lower in BCa tissues than in normal tissues. Besides, copy-number alterations (CNA) of eight TRiC subunits positively regulated their mRNA expressions. Furthermore, high mRNA expression of TCP1/CCT2/CCT4/CCT5/CCT6A/CCT7/CCT8 was significantly associated with poor overall survival (OS) in BCa patients. The eight subunits of the chaperonin TRiC was related to tumor purity and immune infiltration levels of BCa. Co-expression analysis showed CCT6B was negatively associated with other subunits of TRiC and other subunits of TRiC were positively correlated with each other. Additionally, TRiC and their interactive proteins were correlated with positive regulation of biological process, localization, and biological regulation.ConclusionThis study systematically illustrated the expression profiles and distinct prognostic values of chaperonin TRiC in BCa, providing insights for further investigation of subunits of the chaperonin TRiC as novel therapeutic targets and potential prognostic biomarkers in BCa.

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“…The data have been imported to Excel 2019 software to illustrate the Pie chart. Besides, we investigated the genetic alterations of the HPRT1 gene and their impact on the survival outcomes of patients with HNSCC utilizing the data from the cBio Cancer Genomics Portal (http://cbioportal.org) database [27-29]. A log-rank P -value<0.05 was considered as statistically significant.…”

Section: Methodsmentioning

confidence: 99%

Overexpression of HPRT1 is associated with poor prognosis in head and neck squamous cell carcinoma

Ahmadi

Mousavi

Saffarzadeh

et al. 2020

Preprint

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Hypoxanthine phosphoribosyl transferase (HPRT1), as a salvage pathway enzyme, plays a crucial role in modulating the cell cycle and has been reported to be overexpressed in multiple cancers. Nevertheless, the relationship between the HPRT1 and Head and Neck Squamous Cell Carcinomas (HNSCC) has not been investigated so far. We first evaluated the expression of HPRT1 at transcriptomic and proteomic levels in tumor and healthy control tissues and its clinical value using The Cancer Genome Atlas (TCGA), Human Protein Atlas, Kaplan-Meier Plotter databases, GSE107591, and quantitative real-time PCR analysis. Then, we employed the COSMIC and cBioPortal databases to assess the mutations of the HPRT1 gene and their association with survival outcomes of patients with HNSCC. Finally, we performed the functional enrichment analysis for HPRT1 co-expressed genes in HNSCC utilizing the Enrichr database. The mRNA and protein expressions of HPRT1 were significantly elevated in HNSCC compared with normal tissues. Besides, the upregulation of HPRT1 expression was correlated with age, sex, pathological stage, and histological grades of HNSCC patients. Moreover, the increased expression of HPRT1 in cancer tissues exhibited a strong capacity for being a promising biomarker for the diagnosis and prognosis of patients with HNSCC. The co-expressed genes of HPRT1 were mainly enriched in several cancer-related processes such as DNA replication and cell cycle. The present study demonstrated that the overexpression of HPRT1 is significantly correlated with the progression of HNSCC and may serve as a useful biomarker for the early detection and risk stratification of patients with HNSCC.

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Integration and Analysis of CPTAC Proteomics Data in the Context of Cancer Genomics in the cBioPortal

Cited by 138 publications

References 21 publications

Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series

Glycogen Synthase Kinase-3 Beta Expression Correlates With Worse Overall Survival in Non-Small Cell Lung Cancer—A Clinicopathological Series

Systematic Characterization of Expression Profiles and Prognostic Values of the Eight Subunits of the Chaperonin TRiC in Breast Cancer

Overexpression of HPRT1 is associated with poor prognosis in head and neck squamous cell carcinoma

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