Arachidonate lipoxygenases 5 is a novel prognostic biomarker and correlates with high tumor immune infiltration in low-grade glioma

Pan, Ruihan; Zhang, Xin; Chen, Zu-peng; Liu, Yajun

doi:10.3389/fgene.2023.1027690

Cited by 5 publications

(4 citation statements)

References 43 publications

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“…Although previously Nathoo et al demonstrated that 5-LOX is highly expressed in high-grade astrocytomas [88], a comparison with our study cannot be performed considering that we analysed GBM in contrast with astrocytomas, without distinguishing between low-and high-grade astrocytomas. At transcriptional level, gene expression for ALOX5 was increased in both LGG and GBM in comparison to the normal counterpart, as previously already reported [86]. Data from publicly available datasets also showed a significant increase in CD3D, CD3E and SDC1 (CD138) expression in GBM compared to normal tissues, whereas the expression for the same genes was not significantly modulated in LGG when compared to controls indicating that their increased expression could be related to GBM pathogenesis.…”

Section: Discussionsupporting

confidence: 82%

“…In addition, recent evidence showed that 5-LOX can contribute to a proliferative and pro-survival effect in glioma cells through a modulation of ERKs phosphorylation, Bcl-2/Bax signalling and via β-catenin-dependent pathway [74,75,85]. Moreover, a recent publication from Pan et al, showed a positive correlation between 5-LOX expression and tumour immune infiltration in LGG [86]. In line with these findings, we have reported a positive and significant correlation between the tissue expression of 5-LOX and GzmB in GBM samples.…”

Section: Discussionmentioning

confidence: 98%

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Immune cell infiltration and inflammatory landscape in primary brain tumours

Luce,

Abate,

Scognamiglio

et al. 2024

J Transl Med

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Background Primary malignant brain tumours are more than one-third of all brain tumours and despite the molecular investigation to identify cancer driver mutations, the current therapeutic options available are challenging due to high intratumour heterogeneity. In addition, an immunosuppressive and inflammatory tumour microenvironment strengthens cancer progression. Therefore, we defined an immune and inflammatory profiling of meningioma and glial tumours to elucidate the role of the immune infiltration in these cancer types. Methods Using tissue microarrays of 158 brain tumour samples, we assessed CD3, CD4, CD8, CD20, CD138, Granzyme B (GzmB), 5-Lipoxygenase (5-LOX), Programmed Death-Ligand 1 (PD-L1), O-6-Methylguanine-DNA Methyltransferase (MGMT) and Transglutaminase 2 (TG2) expression by immunohistochemistry (IHC). IHC results were correlated using a Spearman correlation matrix. Transcript expression, correlation, and overall survival (OS) analyses were evaluated using public datasets available on GEPIA2 in Glioblastoma (GBM) and Lower Grade Glioma (LGG) cohorts. Results Seven out of ten markers showed a significantly different IHC expression in at least one of the evaluated cohorts whereas CD3, CD4 and 5-LOX were differentially expressed between GBMs and astrocytomas. Correlation matrix analysis revealed that 5-LOX and GzmB expression were associated in both meningiomas and GBMs, whereas 5-LOX expression was significantly and positively correlated to TG2 in both meningioma and astrocytoma cohorts. These findings were confirmed with the correlation analysis of TCGA-GBM and LGG datasets. Profiling of mRNA levels indicated a significant increase in CD3 (CD3D, CD3E), and CD138 (SDC1) expression in GBM compared to control tissues. CD4 and 5-LOX (ALOX5) mRNA levels were significantly more expressed in tumour samples than in normal tissues in both GBM and LGG. In GBM cohort, GzmB (GZMB), SDC1 and MGMT gene expression predicted a poor overall survival (OS). Moreover, in LGG cohort, an increased expression of CD3 (CD3D, CD3E, CD3G), CD8 (CD8A), GZMB, CD20 (MS4A1), SDC1, PD-L1, ALOX5, and TG2 (TGM2) genes was associated with worse OS. Conclusions Our data have revealed that there is a positive and significant correlation between the expression of 5-LOX and GzmB, both at RNA and protein level. Further evaluation is needed to understand the interplay of 5-LOX and immune infiltration in glioma progression.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 98%

Immune cell infiltration and inflammatory landscape in primary brain tumours

Luce,

Abate,

Scognamiglio

et al. 2024

J Transl Med

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“…Tumor-infiltrating immune cells play an essential role in tumor occurrence, progression, and metastasis. Thus, the immune score and stromal score were calculated using the ESTIMATE algorithm [ 25 ]. Besides, the TIMER and xCELL algorithms were adopted to evaluate the expression correlation of TTK with several immune cells.…”

Section: Methodsmentioning

confidence: 99%

TTK is a potential regulator of tumor progression correlated with dedifferentiation and immune cell infiltration in papillary thyroid cancer

Ma,

Xiang,

Wang

2023

Aging

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Objective: To investigate the role and clinical significance of threonine tyrosine kinase (TTK) in papillary thyroid cancer (PTC). Methods: TTK expression in PTC and normal groups were compared using TCGA data and in vitro experiments. The prognostic value of TTK and its possible role in PTC dedifferentiation was evaluated. Next, TTK involvement in PTC occurrence and progression was analyzed via in vitro experiments. Subsequently, analyses of enrichment and immune cell infiltration were conducted to reveal the possible mechanism. Finally, we predicted the target miRNAs followed by performing a luciferase reporter experiment. Results: TTK upregulation was observed in PTC, and its elevated level was significantly related to an unfavorable prognosis ( P < 0.05). Interestingly, TTK negatively correlated with thyroid differentiation score (TDS), and patients with higher TDS showed longer survival (all P < 0.05). PTC cell growth, migration, and invasion were inhibited upon TTK knockdown. Besides, TTK was involved in metabolic processes and regulated cell adhesion molecules pathway. Its overexpression was positively associated with immune cell infiltrates ( P < 0.05). Moreover, miR-582-5p was an upstream target of TTK. Conclusion: TTK serves as a potential biomarker for tumorigenesis and prognosis in PTC, especially for those that may differentiate into more aggressive thyroid cancers.

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“…PGK1 has been reported to promote cancer cell proliferation and migration in NSCLC through the downstream ERK/MCM4 pathway [94]. ALOX5 is generally downregulated in NSCLC [95], and its overexpression has been reported to be associated with tumor progression in gliomas [96].…”

Section: Nf-κb Target Genes' Activation Signature Following Irradiati...mentioning

confidence: 99%

NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia

Nisar,

Sanchidrián González,

Labonté

et al. 2024

IJMS

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Cellular hypoxia, detectable in up to 80% of non-small cell lung carcinoma (NSCLC) tumors, is a known cause of radioresistance. High linear energy transfer (LET) particle radiation might be effective in the treatment of hypoxic solid tumors, including NSCLC. Cellular hypoxia can activate nuclear factor κB (NF-κB), which can modulate radioresistance by influencing cancer cell survival. The effect of high-LET radiation on NF-κB activation in hypoxic NSCLC cells is unclear. Therefore, we compared the effect of low (X-rays)- and high (12C)-LET radiation on NF-κB responsive genes’ upregulation, as well as its target cytokines’ synthesis in normoxic and hypoxic A549 NSCLC cells. The cells were incubated under normoxia (20% O2) or hypoxia (1% O2) for 48 h, followed by irradiation with 8 Gy X-rays or 12C ions, maintaining the oxygen conditions until fixation or lysis. Regulation of NF-κB responsive genes was evaluated by mRNA sequencing. Secretion of NF-κB target cytokines, IL-6 and IL-8, was quantified by ELISA. A greater fold change increase in expression of NF-κB target genes in A549 cells following exposure to 12C ions compared to X-rays was observed, regardless of oxygenation status. These genes regulate cell migration, cell cycle, and cell survival. A greater number of NF-κB target genes was activated under hypoxia, regardless of irradiation status. These genes regulate cell migration, survival, proliferation, and inflammation. X-ray exposure under hypoxia additionally upregulated NF-κB target genes modulating immunosurveillance and epithelial-mesenchymal transition (EMT). Increased IL-6 and IL-8 secretion under hypoxia confirmed NF-κB-mediated expression of pro-inflammatory genes. Therefore, radiotherapy, particularly with X-rays, may increase tumor invasiveness in surviving hypoxic A549 cells.

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Arachidonate lipoxygenases 5 is a novel prognostic biomarker and correlates with high tumor immune infiltration in low-grade glioma

Cited by 5 publications

References 43 publications

Immune cell infiltration and inflammatory landscape in primary brain tumours

Immune cell infiltration and inflammatory landscape in primary brain tumours

TTK is a potential regulator of tumor progression correlated with dedifferentiation and immune cell infiltration in papillary thyroid cancer

NF-κB in the Radiation Response of A549 Non-Small Cell Lung Cancer Cells to X-rays and Carbon Ions under Hypoxia

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