Prognostic significance of HSF2BP in lung adenocarcinoma

Huang, Zhun; Liu, Zhendong; Cheng, Xingbo; Han, Zhibin; Li, Jiwei; Xia, Tian; Gao, Yanzheng; Li, Wei

doi:10.21037/atm-21-4935

Cited by 5 publications

(3 citation statements)

References 45 publications

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“…Pathway and function identified by KEGG included cell cycle and p53 signaling pathway. Previous studies have confirmed that these pathways are related to the occurrence, development, and drug resistance seen in LUAD patients (Huang et al, 2021;Zhu et al, 2021).…”

Section: Discussionmentioning

confidence: 70%

Integrated Bioinformatics Analysis Identifies a New Stemness Index-Related Survival Model for Prognostic Prediction in Lung Adenocarcinoma

Hou

Liu

et al. 2022

Front. Genet.

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Background: Lung adenocarcinoma (LUAD) is one of the most lethal malignancies and is currently lacking in effective biomarkers to assist in diagnosis and therapy. The aim of this study is to investigate hub genes and develop a risk signature for predicting prognosis of LUAD patients. Methods: RNA-sequencing data and relevant clinical data were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was performed to identify hub genes associated with mRNA expression-based stemness indices (mRNAsi) in TCGA. We utilized LASSO Cox regression to assemble our predictive model. To validate our predictive model, me applied it to an external cohort. Results: mRNAsi index was significantly associated with the tissue type of LUAD, and high mRNAsi scores may have a protective influence on survival outcomes seen in LUAD patients. WGCNA indicated that the turquoise module was significantly correlated with the mRNAsi. We identified a 9-gene signature (CENPW, MCM2, STIL, RACGAP1, ASPM, KIF14, ANLN, CDCA8, and PLK1) from the turquoise module that could effectively identify a high-risk subset of these patients. Using the Kaplan-Meier survival curve, as well as the time-dependent receiver operating characteristic (tdROC) analysis, we determined that this gene signature had a strong predictive ability (AUC = 0.716). By combining the 9-gene signature with clinicopathological features, we were able to design a predictive nomogram. Finally, we additionally validated the 9-gene signature using two external cohorts from GEO and the model proved to be of high value. Conclusion: Our study shows that the 9-gene mRNAsi-related signature can predict the prognosis of LUAD patient and contribute to decisions in the treatment and prevention of LUAD patients.

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Section: Discussionmentioning

confidence: 70%

Integrated Bioinformatics Analysis Identifies a New Stemness Index-Related Survival Model for Prognostic Prediction in Lung Adenocarcinoma

Hou

Liu

et al. 2022

Front. Genet.

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“…In the mentioned study, HSF2BP was upregulated in hypoxia-induced GBM, but no follow-up was performed for this gene ( Bhushan et al, 2021 ). Nevertheless, a study on lung adenocarcinoma indicated that HSF2BP forecasts unfavorable patients’ survival and promotes genomic instability ( Huang et al, 2021 ). It is worth noting that such instability may be driven by tumor hypoxia ( Tang et al, 2021 ), which could be considered a valuable hint for future research.…”

Section: Resultsmentioning

confidence: 99%

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

Kałuzińska-Kołat,

Kołat,

Kośla

et al. 2023

Front. Neurosci.

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IntroductionGlioblastoma (GBM) is notorious for its clinical and molecular heterogeneity, contributing to therapeutic failure and a grim prognosis. WWOX is one of the tumor suppressor genes important in nervous tissue or related pathologies, which was scarcely investigated in GBM for reliable associations with prognosis or disease progression despite known alterations. Recently, we observed a phenotypic heterogeneity between GBM cell lines (U87MG, T98G, U251MG, DBTRG-05MG), among which the anti-GBM activity of WWOX was generally corresponding, but colony growth and formation were inconsistent in DBTRG-05MG. This prompted us to investigate the molecular landscapes of these cell lines, intending to translate them into the clinical context.MethodsU87MG/T98G/U251MG/DBTRG-05MG were subjected to high-throughput sequencing, and obtained data were explored via weighted gene co-expression network analysis, differential expression analysis, functional annotation, and network building. Following the identification of the most relevant DBTRG-distinguishing driver genes, data from GBM patients were employed for, e.g., differential expression analysis, survival analysis, and principal component analysis.ResultsAlthough most driver genes were unique for each cell line, some were inversely regulated in DBTRG-05MG. Alongside driver genes, the differentially-expressed genes were used to build a WWOX-related network depicting protein–protein interactions in U87MG/T98G/U251MG/DBTRG-05MG. This network revealed processes distinctly regulated in DBTRG-05MG, e.g., microglia proliferation or neurofibrillary tangle assembly. POLE4 and HSF2BP were selected as DBTRG-discriminating driver genes based on the gene significance, module membership, and fold-change. Alongside WWOX, POLE4 and HSF2BP expression was used to stratify patients into cell lines-resembling groups that differed in, e.g., prognosis and treatment response. Some differences from a WWOX-related network were certified in patients, revealing genes that clarify clinical outcomes. Presumably, WWOX overexpression in DBTRG-05MG resulted in expression profile change resembling that of patients with inferior prognosis and drug response. Among these patients, WWOX may be inaccessible for its partners and does not manifest its anti-cancer activity, which was proposed in the literature but not regarding glioblastoma or concerning POLE4 and HSF2BP.ConclusionCell lines data enabled the identification of patients among which, despite high expression of WWOX tumor suppressor, no advantageous outcomes were noted due to the cancer-promoting profile ensured by other genes.

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“…Current reports of HSF2BP mainly focus on meiosis, spermatogenesis and homologous recombination repair [ 22 , 23 ]. Besides, HSF2BP has been reported to be transcribed in all cultured human cancer cell lines and elevated in some tumor samples [ 19 , 24 ]. Inactivation of the hsf2bp gene in mice leads to male infertility [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

HSF2BP protects against acute liver injury by regulating HSF2/HSP70/MAPK signaling in mice

Zhang

et al. 2022

Cell Death Dis

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Heat shock proteins (HSPs) depletion and protein misfolding are important causes of hepatocyte death and liver regeneration disorder in liver injury. HSF2BP, as its name implies, is a binding protein of HSF2, but the specific role of HSF2BP in heat shock response (HSR) remains unknown. The aim of this study is to identify the role of HSF2BP in HSR and acute liver injury. In this study, we found that HSF2BP expression increased significantly within 24 h after APAP administration, and the trend was highly consistent with that of HSP70. hsf2bp-KO and hsf2bp-TG mouse models demonstrated HSF2BP reduced hepatocyte death, ameliorated inflammation, and improved liver function in APAP- or D-GalN/LPS- induced liver injury. Meanwhile, a significant increase of the survival rate was observed in hsf2bp-TG mice after APAP administration. Further studies showed that HSF2BP upregulated the expression of HSF2 and HSP70 and inhibited the activation of Jnk1/2 and P38 MAPK. Additionally, HSP70 siRNA pretreatment abolished the effect of HSF2BP on the MAPK pathway in APAP-treated hepatocytes. The results reveal that HSF2BP is a protective factor in acute liver injury, and the HSF2BP/HSP70/MAPK regulatory axis is crucial for the pathogenesis of liver injury. HSF2BP is a potential therapeutic target for liver injury.

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Prognostic significance of HSF2BP in lung adenocarcinoma

Cited by 5 publications

References 45 publications

Integrated Bioinformatics Analysis Identifies a New Stemness Index-Related Survival Model for Prognostic Prediction in Lung Adenocarcinoma

Integrated Bioinformatics Analysis Identifies a New Stemness Index-Related Survival Model for Prognostic Prediction in Lung Adenocarcinoma

Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit from WWOX tumor suppressor expression

HSF2BP protects against acute liver injury by regulating HSF2/HSP70/MAPK signaling in mice

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