Identifies microtubule-binding protein CSPP1 as a novel cancer biomarker associated with ferroptosis and tumor microenvironment

Wang, Wenwen; Zhang, Jingjing; Wang, Yuqing; Yan, Xu; Zhang, Shirong

doi:10.1016/j.csbj.2022.06.046

Cited by 40 publications

(20 citation statements)

References 71 publications

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“…Six distinctive CAF clusters were identified, which might exert enormous influence on divergent biological regulation of the TME. Accumulating evidence has confirmed that CAF-related gene signature has great prognostic value in ESCC ( 37 , 38 ). Correspondingly, three clusters in our data were found significantly associated with ESCC prognosis.…”

Section: Discussionmentioning

confidence: 98%

A fibroblast-associated signature predicts prognosis and immunotherapy in esophageal squamous cell cancer

Ren

Zhang

et al. 2023

Front. Immunol.

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BackgroundCurrent paradigms of anti-tumor therapies are not qualified to evacuate the malignancy ascribing to cancer stroma’s functions in accelerating tumor relapse and therapeutic resistance. Cancer-associated fibroblasts (CAFs) has been identified significantly correlated with tumor progression and therapy resistance. Thus, we aimed to probe into the CAFs characteristics in esophageal squamous cancer (ESCC) and construct a risk signature based on CAFs to predict the prognosis of ESCC patients.MethodsThe GEO database provided the single-cell RNA sequencing (scRNA-seq) data. The GEO and TCGA databases were used to obtain bulk RNA-seq data and microarray data of ESCC, respectively. CAF clusters were identified from the scRNA-seq data using the Seurat R package. CAF-related prognostic genes were subsequently identified using univariate Cox regression analysis. A risk signature based on CAF-related prognostic genes was constructed using Lasso regression. Then, a nomogram model based on clinicopathological characteristics and the risk signature was developed. Consensus clustering was conducted to explore the heterogeneity of ESCC. Finally, PCR was utilized to validate the functions that hub genes play on ESCC.ResultsSix CAF clusters were identified in ESCC based on scRNA-seq data, three of which had prognostic associations. A total of 642 genes were found to be significantly correlated with CAF clusters from a pool of 17080 DEGs, and 9 genes were selected to generate a risk signature, which were mainly involved in 10 pathways such as NRF1, MYC, and TGF-Beta. The risk signature was significantly correlated with stromal and immune scores, as well as some immune cells. Multivariate analysis demonstrated that the risk signature was an independent prognostic factor for ESCC, and its potential in predicting immunotherapeutic outcomes was confirmed. A novel nomogram integrating the CAF-based risk signature and clinical stage was developed, which exhibited favorable predictability and reliability for ESCC prognosis prediction. The consensus clustering analysis further confirmed the heterogeneity of ESCC.ConclusionThe prognosis of ESCC can be effectively predicted by CAF-based risk signatures, and a comprehensive characterization of the CAF signature of ESCC may aid in interpreting the response of ESCC to immunotherapy and offer new strategies for cancer treatment.

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Section: Discussionmentioning

confidence: 98%

A fibroblast-associated signature predicts prognosis and immunotherapy in esophageal squamous cell cancer

Ren

Zhang

et al. 2023

Front. Immunol.

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“…MSI is characterized by abnormal microsatellite sequences caused by impaired DNA mismatch repair, which is associated with an increased risk of developing cancer [43]. High-frequency MSI in colorectal cancer is an independent predictor of clinical features and prognosis [44]. Both TMB and MSI are also intrinsically linked to the sensitivity of ICP inhibitors [27].…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of the Prognostic and Immunological Role of SMG5: A Biomarker for Cancers

Yang,

Wei,

et al. 2023

Oncology

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Introduction: SMG5 is involved in tumor cell development and viewed as a potential target for immunotherapy. The purpose of this study was to systematically analyze the expression level, function, and prognostic value of SMG5 in pan-cancers. Methods: Differential expression of SMG5 in normal and tumor tissues was analyzed using The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Database (GTEx) data. Survival analysis was performed by Kaplan-Meier method and Cox risk regression. The relationship between SMG5 expression and lymphocyte abundance, tumor cell immune infiltration level, molecular and immune subtypes as well as immune checkpoints was analyzed by tumor-immune system interactions database (TISIDB), Tumor Immune Estimation Resource (TIMER), and Sangerbox databases. The correlation between SMG5 and immune scores was studied using the Estimation of Stromal and Immune Cells in Malignant Tumours using Expression (ESTIMATE) data algorithm. Further, drug sensitivity analysis of SMG5 with low-grade glioma (LGG) was conducted using the CellMiner database. Results: SMG5 was highly expressed in 23 tumors and only had a significant impact on the prognosis of patients with LGG only. In addition, in tumor microenvironment and tumor immune analysis, we found that the level of immune infiltration, tumor mutational load, microsatellite instability, and immune checkpoints of LGG were significantly correlated with SMG5 expression. Furthermore, SMG5 was significantly associated with immune scores, stromal scores, and sensitivity of some drugs in LGG. Conclusion: SMG5 is differentially expressed in several cancers and is significantly associated with prognosis, immune microenvironment, and immune checkpoints in LGG patients. Therefore, SMG5 could be a potential pan-cancer biomarker and an immunotherapeutic target for LGG.

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“…Ferroptosis biomarkers for renal carcinoma have also undergone significant development. For instance, the protein CSPP1 that binds to microtubules shows potential to be a new cancer biomarker linked to ferroptosis and the tumor microenvironment [102]. FRGsig was shown to be a possible biomarker for predicting the response to immune checkpoint blockade therapy in ccRCC and kidney papillary cell carcinoma, and a high FRGsig was related to a greater response to anti-VEGF therapy in kidney papillary cell carcinoma patients [103].…”

Section: Ferroptosis and Kidney Diseasesmentioning

confidence: 99%

Novel Insight into Ferroptosis in Kidney Diseases

Liu¹,

Liu²,

Zhou³

et al. 2023

Am J Nephrol

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Background: Various kidney diseases such as acute kidney injury, chronic kidney disease, polycystic kidney disease, renal cancer, and kidney stones, are an important part of the global burden, bringing a huge economic burden to people around the world. Ferroptosis is a type of nonapoptotic iron-dependent cell death caused by the excess of iron-dependent lipid peroxides and accompanied by abnormal iron metabolism and oxidative stress. Over the past few decades, several studies have shown that ferroptosis is associated with many types of kidney diseases. Studying the mechanism of ferroptosis and related agonists and inhibitors may provide new ideas and directions for the treatment of various kidney diseases. Summary: In this review, we discuss the differences between ferroptosis and other types of cell death such as apoptosis, necroptosis, pyroptosis, cuprotosis, pathophysiological features of the kidney, and ferroptosis-induced kidney injury. We also provide an overview of the molecular mechanisms involved in ferroptosis and events that lead to ferroptosis. Furthermore, we summarize the possible clinical applications of this mechanism among various kidney diseases. Key Message: The current research suggests that future therapeutic efforts to treat kidney ailments would benefit from a focus on ferroptosis.

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Identifies microtubule-binding protein CSPP1 as a novel cancer biomarker associated with ferroptosis and tumor microenvironment

Cited by 40 publications

References 71 publications

A fibroblast-associated signature predicts prognosis and immunotherapy in esophageal squamous cell cancer

A fibroblast-associated signature predicts prognosis and immunotherapy in esophageal squamous cell cancer

Pan-Cancer Analysis of the Prognostic and Immunological Role of <i>SMG5</i>: A Biomarker for Cancers

Novel Insight into Ferroptosis in Kidney Diseases

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