Identification of an anaplastic subtype of prostate cancer amenable to therapies targeting SP1 or translation elongation

Zou, Cheng; Li, Wenchao; Zhang, Yuanzhen; Feng, Ninghan; Chen, Saisai; Yan, Lianlian; He, Qinju; Wang, Kai; Li, Wenjun; Li, Yingying; Wang, Yang; Xu, Bin; Zhang, Dingxiao

doi:10.1126/sciadv.adm7098

Cited by 4 publications

(1 citation statement)

References 61 publications

(109 reference statements)

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“…Interestingly, we observed lower Sp1 expression in certain cancers, particularly those associated with hormones, such as BRCA, PRAD, THCA and UCEC. While Sp1 has been reported to regulate several hormone receptors, which may in uence treatment outcomes with endocrine therapies, the speci c mechanisms remain unclear and warrant further investigation [28][29][30][31][32] .…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis of Sp1 with a focus on immunological roles in gastric cancer

Zhou,

Luo,

Guo

et al. 2024

Preprint

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Background Sp1, a transcription factor, plays a pivotal role in tumorigenesis across diverse cancers. However, its comprehensive pan-cancer analyses and immunological roles in gastric cancer (GC) remain inadequately elucidated. Methods Through a comprehensive analysis utilizing bioinformatics tools and datasets from TCGA, GEO, and THPA, we examined the multifaceted role of Sp1. Expression profiles were assessed across cell lines, tissues, and tumors, alongside exploration of genetic alterations, DNA methylation, and protein phosphorylation. Its associations with immune infiltration, tumor mutational burden, and immune checkpoint signaling were investigated. Additionally, single-cell transcriptome data showed its expression in different immune cells in GC. Validation of correlations between Sp1 and immune microenvironment in GC was performed using immunohistochemistry and multiple immunofluorescence in an immunotherapy-treated patient cohort. The prognostic value of Sp1 in GC receiving immunotherapy was evaluated with Cox regression model. Results Elevated Sp1 levels were observed in various cancers compared to normal tissues, with notable prominence in gastric cancer. High Sp1 expression correlated with advanced stage, poor prognosis, elevated tumor mutational burden (TMB), and microsatellite instability (MSI) status, particularly in GC. Sp1 levels also correlated with CD8 + T cell and M1 phenotype of tumor-associated macrophages infiltration. Furthermore, GC patients with higher Sp1 levels exhibited improved response to immunotherapy. Moreover, Sp1 emerged as a prognostic and predictive biomarker for GC patients undergoing immunotherapy. Conclusions Our pan-cancer analysis sheds light on Sp1's multifaceted role in tumorigenesis and underscores its potential as a prognostic and predictive biomarker for GC patients undergoing immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis of Sp1 with a focus on immunological roles in gastric cancer

Zhou,

Luo,

Guo

et al. 2024

Preprint

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Integrative analysis of transcriptome, DNA methylome, and chromatin accessibility reveals candidate therapeutic targets in hypertrophic cardiomyopathy

Gao,

Liu,

et al. 2024

Protein &Amp; Cell

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Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is characterized by primary left ventricular hypertrophy usually caused by mutations in sarcomere genes. The mechanism underlying cardiac remodeling in HCM remains incompletely understood. An investigation of HCM through integrative analysis at multi-omics levels will be helpful for treating HCM. DNA methylation and chromatin accessibility, as well as gene expression, were assessed by nucleosome occupancy and methylome sequencing (NOMe-seq) and RNA-seq, respectively, using the cardiac tissues of HCM patients. Compared with those of the controls, the transcriptome, DNA methylome and chromatin accessibility of the HCM myocardium showed multifaceted differences. At the transcriptome level, HCM hearts returned to the fetal gene program through decreased sarcomeric and metabolic gene expression and increased extracellular matrix gene expression. In the DNA methylome, hypermethylated and hypomethylated differentially methylated regions (DMRs) were identified in HCM. At the chromatin accessibility level, HCM hearts showed changes in different genome elements. Several transcription factors (TFs), including SP1 and EGR1, exhibited a fetal-like pattern of binding motifs in nucleosome-depleted regions (NDRs) in HCM. In particular, the inhibition of SP1 or EGR1 in an HCM mouse model harboring sarcomere mutations markedly alleviated the HCM phenotype of the mutant mice and reversed fetal gene reprogramming. Overall, this study not only provides a high precision multi-omics map of HCM heart tissue but also sheds light on the therapeutic strategy by intervening the fetal gene reprogramming in HCM.

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Pan-cancer analysis of Sp1 with a focus on immunomodulatory roles in gastric cancer

Zhou,

Luo,

Guo

et al. 2024

Cancer Cell Int

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Background Sp1, a transcription factor, regulates essential cellular processes and plays important tumorigenic roles across diverse cancers. However, comprehensive pan-cancer analyses of its expression and potential immunomodulatory roles remain unexplored. Methods Utilizing bioinformatics tools and public datasets, we examined the expression of Sp1 across normal tissues, tumors, and immune cells, and screened for pre- and post-transcriptional modifications, including genetic alterations, DNA methylation, and protein phosphorylation, affecting its expression or function. The association of Sp1 expression with immune cell infiltration, tumor mutational burden, and immune checkpoint signaling was also investigated. Single-cell transcriptome data was used to assess Sp1 expression in immune cells in gastric cancer (GC), and findings were corroborated using immunohistochemistry and multiplex immunofluorescence in an immunotherapy-treated patient cohort. The prognostic value of Sp1 in GC patients receiving immunotherapy was evaluated with Cox regression models. Results Elevated Sp1 levels were observed in various cancers compared to normal tissues, with notable prominence in GC. High Sp1 expression correlated with advanced stage, poor prognosis, elevated tumor mutational burden (TMB), and microsatellite instability (MSI) status, particularly in GC. Significant correlations between Sp1 levels and CD8+ T cell and the M1 phenotype of tumor-associated macrophages were further detected upon multiplex immunofluorescence in GC samples. Interestingly, we verified that GC patients with higher Sp1 levels exhibited improved response to immunotherapy. Moreover, Sp1 emerged as a prognostic and predictive biomarker for GC patients undergoing immunotherapy. Conclusions Our pan-cancer analysis sheds light on the multifaceted role of Sp1 in tumorigenesis and underscores its potential as a prognostic and predictive biomarker for patients with GC undergoing immunotherapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-024-03521-z.

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Identification of an anaplastic subtype of prostate cancer amenable to therapies targeting SP1 or translation elongation

Cited by 4 publications

References 61 publications

Pan-cancer analysis of Sp1 with a focus on immunological roles in gastric cancer

Pan-cancer analysis of Sp1 with a focus on immunological roles in gastric cancer

Integrative analysis of transcriptome, DNA methylome, and chromatin accessibility reveals candidate therapeutic targets in hypertrophic cardiomyopathy

Pan-cancer analysis of Sp1 with a focus on immunomodulatory roles in gastric cancer

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