Comprehensive analysis of the prognostic and role in immune cell infiltration of <scp>MSR1</scp> expression in <scp>lower‐grade</scp> gliomas

Ji, Qiankun; Huang, Kai; Jiang, Yuan; Lei, Kunjian; Tu, Zewei; Luo, Haitao; Zhu, Xingen

doi:10.1002/cam4.4603

Cited by 13 publications

(12 citation statements)

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“…We hypothesized that overactivation or increased expression levels of MSR1 and BIRC5 could promote malignant behavior in LGG.Evidences have revealed that BIRC5 can promote cell proliferation and anti-apoptosis in gliomas [ 35 ]. MSR1 is a marker of M2 macrophages, and has been shown higher expression in patients with gbm compared to those with grade II gliomas, which indicated that MSR1 may exert cancer-promoting effects [ 36 , 37 ]. To verify the screened robust m1A-RDEIGs (MSR1 and BIRC5) in LGG and corresponding normal cell lines.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG)

Lei,

Sheng,

Luo

et al. 2024

Heliyon

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Section: Resultsmentioning

confidence: 99%

Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG)

Lei,

Sheng,

Luo

et al. 2024

Heliyon

Self Cite

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“…CD80 or CTLA4 is a known co-inhibitory receptor present in Tregs and antibodies targeting this protein like ipilimumab has shown to produce clinical activity. MSR1 has been described as present in M2 macrophages contributing to inflammation and patient outcome 27 , 28 . Indeed, presence of MSR1 has been linked with T cell exhaustion and it has been included in a gene signature that predicted favorable response to anti PD (L)1 in liver cancer 29 .…”

Section: Discussionmentioning

confidence: 99%

T-reg transcriptomic signatures identify response to check-point inhibitors

Noblejas-López,

García-Gil,

Pérez-Segura

et al. 2024

Sci Rep

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Regulatory T cells (Tregs) is a subtype of CD4+ T cells that produce an inhibitory action against effector cells. In the present work we interrogated genomic datasets to explore the transcriptomic profile of breast tumors with high expression of Tregs. Only 0.5% of the total transcriptome correlated with the presence of Tregs and only four transcripts, BIRC6, MAP3K2, USP4 and SMG1, were commonly shared among the different breast cancer subtypes. The combination of these genes predicted favorable outcome, and better prognosis in patients treated with checkpoint inhibitors. Twelve up-regulated genes coded for proteins expressed at the cell membrane that included functions related to neutrophil activation and regulation of macrophages. A positive association between MSR1 and CD80 with macrophages in basal-like tumors and between OLR1, ABCA1, ITGAV, CLEC5A and CD80 and macrophages in HER2 positive tumors was observed. Expression of some of the identified genes correlated with favorable outcome and response to checkpoint inhibitors: MSR1, CD80, OLR1, ABCA1, TMEM245, and ATP13A3 predicted outcome to anti PD(L)1 therapies, and MSR1, CD80, OLR1, ANO6, ABCA1, TMEM245, and ATP13A3 to anti CTLA4 therapies, including a subgroup of melanoma treated patients. In this article we provide evidence of genes strongly associated with the presence of Tregs that modulates the response to check point inhibitors.

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“…MSR1 demonstrated a 6-fold increase (mRNA expression of 2.3 ± 0.07, p < 0.0001) and CD86 showed an 8.9-fold increase in expression (mRNA expression of 2.41 ± 0.06, p < 0.0001) in LGG tumors. Expression of the M2-like TAM marker MSR1/CD204 [ 37 ] was found to be an independent prognostic factor for LGG patients and may play a vital role in their immunotherapy [ 41 ]. CD86 is expressed on M1-like and M2b-like macrophages [ 23 , 37 ] and may contribute to an immunosuppressive TME through activation of CD4+FoxP3+ regulatory T cells (Treg) [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas

Trieu,

Maida,

Qazi

2024

Cancers

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LGG tumors are characterized by a low infiltration of immune cells, requiring therapeutic interventions to boost the immune response. We conducted a study analyzing mRNA expression datasets from the UCSC Xena web platform. To screen for upregulated genes, we sought to compare normal brain tissue with LGG tumor samples. We also used cBioportal to determine the relationship between mRNA expression levels of 513 LGG patients and their overall survival (OS) outcomes. Three tumor-associated macrophage (TAM) markers, MSR1/CD204, CD86, and CD68, exhibited a 6-fold (p < 0.0001), 8.9-fold (p < 0.0001), and 15.6-fold increase in mRNA expression levels, respectively, in LGG tumors. In addition, both TGFB1 (4.1-fold increase, p < 0.0001) and TGFB2 (2.2-fold increase, p < 0.0001) ligands were also upregulated in these tumors compared to normal brain tissue, suggesting that TGFB ligands are pivotal in establishing an immunosuppressive, angiogenic, and pro-tumorigenic TME in gliomas mediated through TAMs. In addition, mRNA upregulation of interferon-gamma receptors, IFNGR1 and IFNGR2, and the downstream signaling molecules STAT1, IRF1, and IRF5, pointed to an essential role for IFN-γ mediated remodeling of the TME. Interestingly, the mRNA expression of a tumor-associated antigen, CD276/B7-H3, showed a significant (p < 0.0001) 4.03-fold increase in tumor tissue, giving further insights into the roles of macrophages and tumor cells in supporting the immunosuppressive TME. Multivariate Cox proportional hazards models investigating the interaction of TGFB2 and activation of IFNGR2, STAT1, IRF1, or IRF5 showed that the prognostic impact of high mRNA levels (25th percentile cut-off) of TGFB2 was independent of IFNGR2, STAT1, IRF1, or IRF5 mRNA levels (TGFB2high HR (95% CI) = 4.07 (2.35–7.06), 6 (3.62–10.11), 4.38 (2.67–7.17), and 4.48 (2.82–7.12) for models with IFNGR2, STAT1, IRF1, or IRF5, respectively) and age at diagnosis. Patients with high levels of TGFB2 and IFNGR2 were over-represented by LGG patients with isocitrate dehydrogenase wild-type (IDHwt) mutation status. The prognostic impact of high levels of TGFB2 and IDH wild-type observed by the increases in hazard ratios for TGFB2 (HR (95% CI range) = 2.02 (1.05–3.89)) and IDH wild-type (HR (95% CI range) = 4.44 (1.9–10.4)) were independent predictors of survival, suggesting that risk stratification of patients identifies LGG patients with IDH wild-type and high levels of TGFB2 in the design of clinical trials. Furthermore, we have additional IRF5 and CD276/B7-H3 as prognostic markers that can also be targeted for combination therapies with TGFB2 inhibitors. In support of these findings, we demonstrated that low levels of gene methylation in TGFB2, IFNGR2, IRF1, IRF5, STAT1, and CD276 were associated with significantly worse overall survival (OS) outcomes. This suggests that potential mechanisms to increase the expression of these prognostic markers occur via the action of demethylation enzymes.

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Comprehensive analysis of the prognostic and role in immune cell infiltration of MSR1 expression in lower‐grade gliomas

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 13 publications

References 56 publications

Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG)

Comprehensive analyses of m1A regulator-mediated modification patterns determining prognosis in lower-grade glioma (running title: m1A in LGG)

T-reg transcriptomic signatures identify response to check-point inhibitors

Transforming Growth Factor Beta 2 (TGFB2) mRNA Levels, in Conjunction with Interferon-Gamma Receptor Activation of Interferon Regulatory Factor 5 (IRF5) and Expression of CD276/B7-H3, Are Therapeutically Targetable Negative Prognostic Markers in Low-Grade Gliomas

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