A CD8+ T cell-associated immune gene panel for prediction of the prognosis and immunotherapeutic effect of melanoma

Sun, Shanwen; Zhi, Zhengke; Su, Yang; Sun, Jian; Li, Qianjun

doi:10.3389/fimmu.2022.1039565

Cited by 4 publications

(3 citation statements)

References 47 publications

(48 reference statements)

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“…RSAD2—RSAD2 is involved the cellular signal for the immune response and inflammation ( Sun et al, 2022 ). A reduction in RSAD2 expression in metastatic responders compared to non-responders to FOLFOX (logFC = −2.30) is observed.…”

Section: Discussionmentioning

confidence: 99%

High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data

Amniouel,

Jafri

2024

Front. Physiol.

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Introduction: FOLFOX and FOLFIRI chemotherapy are considered standard first-line treatment options for colorectal cancer (CRC). However, the criteria for selecting the appropriate treatments have not been thoroughly analyzed.Methods: A newly developed machine learning model was applied on several gene expression data from the public repository GEO database to identify molecular signatures predictive of efficacy of 5-FU based combination chemotherapy (FOLFOX and FOLFIRI) in patients with CRC. The model was trained using 5-fold cross validation and multiple feature selection methods including LASSO and VarSelRF methods. Random Forest and support vector machine classifiers were applied to evaluate the performance of the models.Results and Discussion: For the CRC GEO dataset samples from patients who received either FOLFOX or FOLFIRI, validation and test sets were >90% correctly classified (accuracy), with specificity and sensitivity ranging between 85%-95%. In the datasets used from the GEO database, 28.6% of patients who failed the treatment therapy they received are predicted to benefit from the alternative treatment. Analysis of the gene signature suggests the mechanistic difference between colorectal cancers that respond and those that do not respond to FOLFOX and FOLFIRI. Application of this machine learning approach could lead to improvements in treatment outcomes for patients with CRC and other cancers after additional appropriate clinical validation.

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Section: Discussionmentioning

confidence: 99%

High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data

Amniouel,

Jafri

2024

Front. Physiol.

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“…In addition to its diagnostic role, RSAD2 can also be used as a prognostic marker for IFN-β therapy in MS [34] . RSAD2 also can predict the prognosis of melanoma in the prediction model of CD8 + T lymphocyte involvement [35] . Therefore, whether RSAD2 can be used as a marker for SLE speci c drug treatment warrants further study.…”

Section: Discussionmentioning

confidence: 99%

IFN-beta promotes RSAD2 expression and Lupus plasma cell differentiation via DNA Demethylation

mei,

Li,

Xin

et al. 2024

Preprint

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Background Systemic lupus erythematosus (SLE) is an autoimmune disease, in which the pathogenesis is revealed as abnormalities in B cells with no clear mechanism. Radical s-adenosyl methionine domain-containing 2 (RSAD2) is an interferon-stimulated gene (ISG), and it has been found to play an important role in innate immunity. Recent years the function of RSAD2 in autoimmune diseases, but its still unknown for RSAD2 in B cells from SLE patients still. Result In this study, we found RSAD2 was abnormal in SLE by analysis of database, which was relative with interferon (IFN). Further, we found that RSAD2 in peripheral blood B cell subsets was generally higher in SLE patients than healthy controls (HCs). In the meantime, differentiated B cells showed significantly higher expression of RSAD2 than naïve B cells in human tonsils. In the functional study in vitro, the frequencies of differentiated B cells and the expression of RSAD2 were enhanced by interferon-β (IFN-β). Simultaneously, the frequency of plasma cells (PC) was significantly reduced in sorted peripheral CD19+ B cells which was knock-down RSAD2 and stimulated with IFN-β. Mechanically, IFN-β can induce the hypomethylation of RSAD2 in B cells in vitro, which might be one of mechanisms for increased expression level of RSAD2 in B cells from SLE patients. Conclusion This study uncovered that IFN-β up-regulated the expression of RSAD2 by down-regulating the methylation of it to promote B cell differentiation.

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“…The data above demonstrates an unusual link between IFNg and lymphoid cells in terms of clinical outcomes as summarized in Figure 7. IFNg and CD8 + T cells are linked to and necessary for the production of high NOS2 and COX2 levels, despite the fact that they are predictive of positive clinical outcomes and a hallmark of a good prognosis in many malignancies (23,28). According to the scRNAseq results, IFNg and IL1b/TNFa are necessary to induce the highest levels of NOS2 and COX2 expression, which suggests that lymphoid cells must be a contributing factor in the tumor.…”

Section: Discussionmentioning

confidence: 99%

Interferon-gamma is Quintessential for NOS2 and COX2 Expression in ER^-Breast Tumors that Lead to Poor Outcome

Cheng

Ridnourl

Wink

et al. 2023

Preprint

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A strong correlation between NOS2 and COX2 tumor expression and poor clinical outcomes in ER- breast cancer has been established. However, mechanisms of tumor induction of these enzymes are unclear. Analysis of The Cancer Genome Atlas (TCGA) revealed correlations between NOS2 and COX2 expression and Th1 cytokines. Herein, single cell RNAseq analysis of TNBC cells shows potent NOS2 and COX2 induction by IFNg combined with IL1b or TNFa. Given that IFNg is secreted by cytolytic lymphocytes, which improve clinical outcomes, this role of IFNg presents a dichotomy. To explore this conundrum, tumor NOS2, COX2, and CD8+ T cells werespatially analyzed in aggressive ER-, TNBC, and HER2+ breast tumors. High expression and clustering of NOS2-expressing tumor cells occurred at the tumor/stroma interface in the presence of stroma restricted CD8+ T cells. High expression and clustering of COX2-expressing tumor cells extended into immune desert regions in the tumor core where CD8+ T cell penetration was limited or absent. Moreover, high NOS2-expressing tumor cells were proximal to areas with increased satellitosis suggestive of cell clusters with a higher metastatic potential. Further in vitro experiments revealed that IFNg+IL1b/TNFa increased elongation and migration of treated tumor cells. This spatial analysis of the tumor microenvironment provides important insight of distinct neighborhoods where stroma-restricted CD8+ T cells exist proximal to NOS2-expressing tumor niches that could have increased metastatic potential.

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A CD8+ T cell-associated immune gene panel for prediction of the prognosis and immunotherapeutic effect of melanoma

Cited by 4 publications

References 47 publications

High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data

High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data

IFN-beta promotes RSAD2 expression and Lupus plasma cell differentiation via DNA Demethylation

Interferon-gamma is Quintessential for NOS2 and COX2 Expression in ER^-Breast Tumors that Lead to Poor Outcome

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A CD8+ T cell-associated immune gene panel for prediction of the prognosis and immunotherapeutic effect of melanoma

Cited by 4 publications

References 47 publications

High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data

High-accuracy prediction of colorectal cancer chemotherapy efficacy using machine learning applied to gene expression data

IFN-beta promotes RSAD2 expression and Lupus plasma cell differentiation via DNA Demethylation

Interferon-gamma is Quintessential for NOS2 and COX2 Expression in ER-Breast Tumors that Lead to Poor Outcome

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Interferon-gamma is Quintessential for NOS2 and COX2 Expression in ER^-Breast Tumors that Lead to Poor Outcome