The fusion of quantitative molecular proteomics and <scp>immune‐oncology</scp>: a step towards precision medicine in cancer therapeutics

Miles, James; Ward, Stephen G.; Larijani, Banafshé

doi:10.1002/1873-3468.14480

Cited by 4 publications

(2 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, immune checkpoint inhibitors (ICIs) have been shown to be one of the most promising and effective immunotherapies, which reconstitute anti-tumor responses and prevent tumor cells from evading immune surveillance by targeting specific molecules, such as programmed death receptor 1 (PD-1) or its ligand (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) 48 – 50 . Our current findings suggest that TOP2A is involved in regulating the expression of immune checkpoint (PD-L1) in NSCLC, and the upregulation of TOP2A significantly promotes the expression of immune checkpoint (PD-L1).…”

Section: Discussionmentioning

confidence: 99%

The role of TOP2A in immunotherapy and vasculogenic mimicry in non-small cell lung cancer and its potential mechanism

Zhang

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Type IIA topoisomerase (TOP2A) is significantly associated with malignant tumor development, invasion, treatment and its prognosis, and has been shown to be a therapeutic target against cancer. In contrast, the role of TOP2A in the immunotherapy of non-small cell lung cancer as well as in Vasculogenic mimicry (VM) formation and its potential mechanisms are unclear. The aim of this study was to investigate the role of TOP2A in proliferation, skeleton regulation, motility and VM production in non-small cell lung cancer and its mechanisms by using bioinformatics tools and molecular biology experiments. Subgroup analysis showed that the low-risk group had a better prognosis, while the high-risk group was positively correlated with high tumor mutational load, M1-type macrophage infiltration, immune checkpoint molecule expression, and immunotherapy efficacy. As confirmed by further clinical specimens, the presence of TOP2A and VM was significantly and positively correlated with poor prognosis. Our study established a model based on significant co-expression of TOP2A genes, which significantly correlated with mutational load and immunotherapy outcomes in patients with non-small cell lung cancer. Further mechanistic exploration suggests that TOP2A plays an important role in immunotherapy and VM formation in NSCLC through upregulation of Wnt3a and PD-L1 expression.

show abstract

Section: Discussionmentioning

confidence: 99%

The role of TOP2A in immunotherapy and vasculogenic mimicry in non-small cell lung cancer and its potential mechanism

Zhang

et al. 2023

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In recent years, immune checkpoint inhibitors (ICIs) have been shown to be one of the most promising and effective immunotherapies, which reconstitute anti-tumor responses and prevent tumor cells from evading immune surveillance by targeting speci c molecules, such as programmed death receptor 1 (PD-1) or its ligand (PD-L1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4) [52][53][54]. Our current ndings suggest that TOP2A is involved in regulating the expression of immune checkpoint (PD-L1) in NSCLC, and the upregulation of TOP2A signi cantly promotes the expression of immune checkpoint (PD-L1).…”

Section: Discussionmentioning

confidence: 99%

The role of TOP2A in immunotherapy and Vasculogenic mimicry in non-small cell lung cancer and its potential mechanism

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Type IIA topoisomerase (TOP2A) is significantly associated with malignant tumor development, invasion, treatment and its prognosis, and has been shown to be a therapeutic target against cancer. In contrast, the role of TOP2A in the immunotherapy of non-small cell lung cancer as well as in VM formation and its potential mechanisms are unclear. Methods: Based on the 82 significantly co-expressed genes of TOP2A screened, consensus molecular typing was performed by the NMF algorithm, and the effect of immunotherapy was further evaluated in two groups of patients with high and low risk. The expression of TOP2A and VM in non-small cell lung cancer tissues was assessed by immunohistochemistry. Western Blot, colony formation assay, CCK8 assay, cell cycle and apoptosis assay, tube-forming assay and cytoskeleton staining were used to verify the role of TOP2A in proliferation, skeleton regulation, motility and VM generation in non-small cell lung cancer and its mechanism. Results: Patients with lung adenocarcinoma were distinguished into high- and low-risk subgroups based on significant co-expression of TOP2A genes. Subgroup analysis showed that patients in the low-risk group had a better prognosis, while higher risk was associated with higher tumor mutational load, M1-type macrophage and immune checkpoint molecule expression. The Tumor Immune Dysfunction and Rejection (TIDE) and Tumor Immunome Atlas (TCIA) databases also showed significant differences in the outcome of immunotherapy in patients with different types of lung adenocarcinoma. As verified by further clinical specimens, the presence of both TOP2A and VM were significantly and positively correlated with poor prognosis. TOP2A may ultimately affect immunotherapy and VM formation in non-small cell lung cancer through its involvement in regulating the expression of Wnt3a and PD-L1. Conclusion: A model based on significantly co-expressed genes of TOP2A was significantly correlated with mutational load and immunotherapeutic effects in patients with non-small cell lung cancer. TOP2A plays an important role in immunotherapy and VM formation in non-small cell lung cancer through upregulation of Wnt3a and PD-L1 expression.

show abstract

Spatial functional mapping of hypoxia inducible factor heterodimerisation and immune checkpoint regulators in clear cell renal cell carcinoma

Safrygina,

Applebee,

McIntyre

et al. 2024

BJC Rep

View full text Add to dashboard Cite

Background Clear cell renal cell carcinoma (ccRCC) is a highly malignant subtype of kidney cancer. Ninety percent of ccRCC have inactivating mutations of VHL that stabilise transcription factors, HIF1α and HIF2α, only stabilised in hypoxia. The varied response to HIF2 inhibition, in the preclinical and clinical settings, suggests that assessment of HIF2α activation state, not just expression levels is required as a biomarker of sensitivity to enable optimal clinical use. Methods Two-site amplified time-resolved Förster Resonance Energy Transfer (aiFRET), with FRET-Efficiency, $$Ef$$ E f , as its read out, provides functional proteomics quantification, a precise step forward from protein expression as a tool for patient stratification. To enhance the clinical accessibility of $$Ef$$ E f , we have devised a new computational approach, Functional Oncology map (FuncOmap). Results FuncOmap directly maps functional states of oncoproteins and allows functional states quantification at an enhanced spatial resolution. The innovative contributions in FuncOmap are the means to co-analyse and map expressional and functional state images and the enhancement of spatial resolution to facilitate clinical application. We show the spatial interactive states HIF2α and HIF1β in ccRCC patient samples. Conclusion FuncOmap can be used to quantify heterogeneity in patient response and improve accurate patient stratification, thus enhancing the power of precision.

show abstract

The fusion of quantitative molecular proteomics and immune‐oncology: a step towards precision medicine in cancer therapeutics

Cited by 4 publications

References 55 publications

The role of TOP2A in immunotherapy and vasculogenic mimicry in non-small cell lung cancer and its potential mechanism

The role of TOP2A in immunotherapy and vasculogenic mimicry in non-small cell lung cancer and its potential mechanism

The role of TOP2A in immunotherapy and Vasculogenic mimicry in non-small cell lung cancer and its potential mechanism

Spatial functional mapping of hypoxia inducible factor heterodimerisation and immune checkpoint regulators in clear cell renal cell carcinoma

Contact Info

Product

Resources

About