Construction and verification of a hypoxia-related nine-gene prognostic model in uveal melanoma based on integrated single-cell and bulk RNA sequencing analyses

Zhang, Xueling; Qiu, Jini; Huang, Feifei; Han, Ping; Shan, K. Y.; Zhang, Chaoran

doi:10.1016/j.exer.2022.109214

Cited by 11 publications

(9 citation statements)

References 37 publications

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“…ScRNA-seq has been instrumental in identifying the subpopulations within heterogenous tumors, and dissect the molecular mechanisms underlying tumor biology [ 40 , 41 ]. Signature genes screened using single-cell transcriptomic data have been used to establish prognostic models that can not only obviate the limitations of tumor heterogeneity, but also predict prognosis with greater accuracy based on target cell subsets [ 42 – 44 ].…”

Section: Discussionmentioning

confidence: 99%

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

Shi¹,

Yan²,

Han³

2023

Oncology Research

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Ovarian cancer (OV) is highly heterogeneous tumor with a very poor prognosis. Studies increasingly show that T cell exhaustion is prognostically relevant in OV. The aim of this study was to dissect the heterogeneity of T cell subclusters in OV through single cell transcriptomic analysis. The single RNA-sequencing (scRNA-seq) data of five OV patients were analyzed, and six major cell clusters were identified after threshold screening. Further clustering of T cell-associated clusters revealed four subtypes. Pathways related to oxidative phosphorylation, G2M checkpoint, JAK-STAT and MAPK signaling were significantly activated, while the p53 pathway was inhibited in the CD8+ exhausted T cells. The standard marker genes of CD8+ T cell exhaustion were screened to develop a T-cell related gene score (TRS) based on random forest plots in TCGA cohort. The patients with low TRS have better prognosis compared to the patients with high TRS in both TCGA and GEO. In addition, most genes included in the TRS showed significant differences in expression levels between the high- and low-risk groups. Immune cell infiltration was analyzed using the MCPcounter and xCell algorithms, which revealed significant differences between the two risk groups, indicating that the different prognoses may stem from the respective immune landscapes. In addition, CD38 knockdown in OV cell lines increased apoptosis and inhibited invasion in vitro . Finally, we performed a drug sensitivity analysis and identified six potential drug candidates for OV. To summarize, we identified the heterogeneity and clinical significance of T cell exhaustion in OV and built a superior prognostic model based on T cell exhaustion genes, which can contribute to the development of more precise and effective therapies.

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Section: Discussionmentioning

confidence: 99%

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

Shi¹,

Yan²,

Han³

2023

Oncology Research

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“…By allowing the examination of cellular heterogeneity at the individual cell level, these techniques provide valuable insights into cellular diversity, clonal evolution, cellular interactions, and disease mechanisms. Consequently, they advance our understanding of complex biological processes and drive the development of targeted therapies and personalized medicine approaches [195,[201][202][203][204][205].…”

Section: Implication Of Single-cell In Ummentioning

confidence: 99%

Heterogeneity and molecular landscape of melanoma: implications for targeted therapy

Beigi,

Lanjanian,

Fayazi

et al. 2024

Mol Biomed

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Uveal cancer (UM) offers a complex molecular landscape characterized by substantial heterogeneity, both on the genetic and epigenetic levels. This heterogeneity plays a critical position in shaping the behavior and response to therapy for this uncommon ocular malignancy. Targeted treatments with gene-specific therapeutic molecules may prove useful in overcoming radiation resistance, however, the diverse molecular makeups of UM call for a patient-specific approach in therapy procedures. We need to understand the intricate molecular landscape of UM to develop targeted treatments customized to each patient's specific genetic mutations. One of the promising approaches is using liquid biopsies, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), for detecting and monitoring the disease at the early stages. These non-invasive methods can help us identify the most effective treatment strategies for each patient. Single-cellular is a brand-new analysis platform that gives treasured insights into diagnosis, prognosis, and remedy. The incorporation of this data with known clinical and genomics information will give a better understanding of the complicated molecular mechanisms that UM diseases exploit. In this review, we focused on the heterogeneity and molecular panorama of UM, and to achieve this goal, the authors conducted an exhaustive literature evaluation spanning 1998 to 2023, using keywords like "uveal melanoma, “heterogeneity”. “Targeted therapies”," "CTCs," and "single-cellular analysis".

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“…A foregoing study represented that HRGs were correlated with immune microenvironment and survival time in UVM [11]. Nevertheless, How HRLs function in UVM was still unde ned.…”

Section: Introductionmentioning

confidence: 99%

“…In UVM, hypoxia has been shown to promote tumor invasion and progression through activation of Notch and MAPK pathways [9,10]. Moreover, HRGs were associated with the prognosis of UVM [11]. Thus, hypoxia is critical in UVM progression.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Related lncRNA Correlates with Prognosis and Immune Microenvironment in Uveal Melanoma

Chen,

Cheng

et al. 2024

Preprint

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Background Genes related to hypoxia are correlated to the prognosis of a variety of solid malignant tumors. However, How hypoxia related lncRNA function in Uveal Melanoma is still rare. Methods From TCGA database, eighty UVM samples were incorporated. Prognostic HRL was screened by COX univariate analysis and Pearson correlation analysis. HRL characteristics were constructed using Lasso analysis. Gene enrichment analysis revealed the linkage of HRLs to immune features. CCK8 assay was adopted to measure the propagation of MuM2B cells, while tumor invasion and migration were appraised by Transwell and Wound-healing experiments. Inflammatory factors and macrophage polarization were evaluated by qPCR. Results 621 prognostic HRLs were screened and was constructed in 12 HRLs. Risk score showed salient correlation with survival time of UVM patients. In addition, HRL was correlated with diverse key immune checkpoints, revealing possible targets for immunotherapy. Immune-related pathways were highly enriched in high-risk group. Protective HRL, LINC02367, was saliently associated with microenvironment and survival time of UVM patients. In vitro assays demonstrated LINC02367 significantly affected the propogation and migration of MuM2B. LINC02367 modulates macrophage polarization through inflammatory factor levels thereby affecting the immune microenvironment Conclusions In our study, a novel HRL signature was developed to predict the prognosis of UVM patients. HRLs are potential biomarkers and therapeutic targets for UVM.

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Construction and verification of a hypoxia-related nine-gene prognostic model in uveal melanoma based on integrated single-cell and bulk RNA sequencing analyses

Cited by 11 publications

References 37 publications

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

System analysis based on the T cell exhaustion‑related genes identifies CD38 as a novel therapy target for ovarian cancer

Heterogeneity and molecular landscape of melanoma: implications for targeted therapy

Hypoxia-Related lncRNA Correlates with Prognosis and Immune Microenvironment in Uveal Melanoma

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