Immune marker signature helps to predict survival in uveal melanoma

Pan, Lisha; Ackbarkha, Zacharia; Zeng, Jing; Huang, Manni; Yang, Zhen; Liang, Hao

doi:10.3934/mbe.2021203

Cited by 6 publications

(7 citation statements)

References 36 publications

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“…After excluding some models with no formula available to calculate the risk score [ 34 – 38 ], 19 mRNA signatures ( Supplementary Table 3 ) were finally enrolled to benchmark the ICDscore. These signatures were relevant to many biological processes, including immune cell infiltration [ 39 , 40 ], autophagy [ 41 ], DNA methylation [ 42 ], necroptosis [ 43 ], pyroptosis [ 44 ], cuproptosis [ 45 ], ferroptosis [ 46 ], epithelial–mesenchymal transition (EMT) [ 47 ], and metabolism [ 48 ]. Univariate Cox analyses indicated that only the ICDscore and other 4 signatures had significant prognostic relevance across the four cohorts ( Figure 5A ).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, the ICDscore was also compared with 19 previously published mRNA risk models ( Figure 5A – 5F ). These signatures had a tight relevance with a number of biological processes, such as immune cell infiltration [ 39 , 40 ], various forms of cell death [ 41 , 43 , 44 ], DNA methylation [ 42 ], epithelial–mesenchymal transition (EMT) [ 47 ], and metabolism [ 48 ]. Univariate Cox regression showed that only the ICDscore and four other signatures exhibited prognostic significance across all studied cohorts [ 47 , 59 – 61 ], indicating most signatures had a weak association with prognosis or had not been thoroughly validated ( Figure 5A ).…”

Section: Discussionmentioning

confidence: 99%

“…After excluding some models with no formula available to calculate the risk score [34][35][36][37][38], 19 mRNA signatures (Supplementary Table 3) were finally enrolled to benchmark the ICDscore. These signatures were relevant to many biological processes, including immune cell infiltration [39,40], autophagy [41], DNA methylation [42], necroptosis [43], pyroptosis [44],…”

Section: Evaluation Of the Icdscore In Uvmmentioning

confidence: 99%

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Identification and validation of immunogenic cell death-related score in uveal melanoma to improve prediction of prognosis and response to immunotherapy

Kang

Jing

et al. 2023

Aging

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Background: Immunogenic cell death (ICD) could activate innate and adaptive immune response. In this work, we aimed to develop an ICD-related signature in uveal melanoma (UVM) patients and facilitate assessment of their prognosis and immunotherapy. Methods: A set of machine learning methods, including non-negative matrix factorization (NMF) method and least absolute shrinkage and selection operator (LASSO) logistic regression model, and bioinformatics analytic tools were integrated to construct an ICD-related risk score (ICDscore). CIBERSORT and ESTIMATE algorithms were used to evaluate the infiltration of immune cells. The Genomics of Drug Sensitivity in Cancer (GDSC), cellMiner and tumor immune dysfunction and exclusion (TIDE) databases were used for therapy sensitivity analyses. The predictive performance between ICDscore with other mRNA signatures was also compared. Results: The ICDscore could predict the prognosis of UVM patients in both the training and four validating cohorts. The ICDscore outperformed 19 previously published signatures. Patients with high ICDscore exhibited a substantial increase in immune cell infiltration and expression of immune checkpoint inhibitor-related genes, leading to a higher response rate to immunotherapy. Furthermore, the downregulation of poly (ADP-ribose) polymerase family member 8 (PARP8), a critical gene involved in the development of the ICDscore, resulted in decreased cell proliferation and slower migration of UVM cells. Conclusion: In conclusion, we developed a robust and powerful ICD-related signature for evaluating the prognosis and benefits of immunotherapy that could serve as a promising tool to guide decision-making and surveillance for UVM patients.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Evaluation Of the Icdscore In Uvmmentioning

confidence: 99%

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Identification and validation of immunogenic cell death-related score in uveal melanoma to improve prediction of prognosis and response to immunotherapy

Kang

Jing

et al. 2023

Aging

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“…Thus, HES6 appears to be a relevant prognostic biomarker in primary uveal melanomas 55 . Supporting this notion is the recent identification of a four-gene signature of prognostic significance in uveal melanoma that includes HES6 57 . Additional evidence for the role of HES6 as a prognostic biomarker has been shown in primary cutaneous melanomas 58 .…”

Section: Hes6 In Cancermentioning

confidence: 96%

Recent advances in understanding the role of HES6 in cancers

et al. 2022

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The NOTCH signaling system regulates a variety of cellular processes during embryonic development and homeostasis maintenance in different tissues and contexts. Hence, dysregulation of NOTCH signaling is associated with a plethora of human cancers, and there have been multiple efforts to target key components of this pathway. In this review, we briefly highlight the latest research advances in understanding HES6, a poorly studied component of the NOTCH pathway. We summarize the role of HES6 in cancers with a focus on uveal melanoma. Finally, we discuss the ongoing efforts to target the NOTCH-HES6 axis in cancers.

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“…These neoloops encompassed HLA-J (Fig. 2a), which has been associated with poorer prognosis in melanoma 56 and breast cancer patients 57 . HLA-J was expressed significantly higher in GSCs carrying neoloops in its locus compared to all other in our cohort (Fig.…”

Section: Gsc-specific Svs Underlie Neo-domain and Neo-loop Formationmentioning

confidence: 99%

Pervasive structural heterogeneity rewires glioblastoma chromosomes to sustain patient-specific transcriptional programs

Xie,

Danieli-Mackay,

Buccarelli

et al. 2024

Nat Commun

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Glioblastoma multiforme (GBM) encompasses brain malignancies marked by phenotypic and transcriptional heterogeneity thought to render these tumors aggressive, resistant to therapy, and inevitably recurrent. However, little is known about how the spatial organization of GBM genomes underlies this heterogeneity and its effects. Here, we compile a cohort of 28 patient-derived glioblastoma stem cell-like lines (GSCs) known to reflect the properties of their tumor-of-origin; six of these were primary-relapse tumor pairs from the same patient. We generate and analyze 5 kbp-resolution chromosome conformation capture (Hi-C) data from all GSCs to systematically map thousands of standalone and complex structural variants (SVs) and the multitude of neoloops arising as a result. By combining Hi-C, histone modification, and gene expression data with chromatin folding simulations, we explain how the pervasive, uneven, and idiosyncratic occurrence of neoloops sustains tumor-specific transcriptional programs via the formation of new enhancer-promoter contacts. We also show how even moderately recurrent neoloops can relate to patient-specific vulnerabilities. Together, our data provide a resource for dissecting GBM biology and heterogeneity, as well as for informing therapeutic approaches.

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Immune marker signature helps to predict survival in uveal melanoma

Cited by 6 publications

References 36 publications

Identification and validation of immunogenic cell death-related score in uveal melanoma to improve prediction of prognosis and response to immunotherapy

Identification and validation of immunogenic cell death-related score in uveal melanoma to improve prediction of prognosis and response to immunotherapy

Recent advances in understanding the role of HES6 in cancers

Pervasive structural heterogeneity rewires glioblastoma chromosomes to sustain patient-specific transcriptional programs

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