The role of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) gene expression in diagnosis and prognosis of acute myeloid leukemia

Gamaleldin, Marwa; Imbaby, Salma Alaa Eldin

doi:10.1007/s11033-021-06682-6

Cited by 8 publications

(5 citation statements)

References 42 publications

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“…The association between TNFRSF4 expression and OS remained significant even after adjusting for multiple clinical factors, indicating that TNFRSF4 expression can independently predict patient outcomes. These results are consistent with previous studies that have reported TNFRSF4 expression as an independent risk factor for poor survival in patients with cancer [ 30 , 31 ]. Moreover, our subgroup analysis revealed a significant interaction between gender and the association of TNFRSF4 expression with OS in patients with HCC.…”

Section: Discussionsupporting

confidence: 93%

Prognostic significance of TNFRSF4 expression and development of a pathomics model to predict expression in hepatocellular carcinoma

Yan,

Li,

et al. 2024

Heliyon

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Section: Discussionsupporting

confidence: 93%

Prognostic significance of TNFRSF4 expression and development of a pathomics model to predict expression in hepatocellular carcinoma

Yan,

Li,

et al. 2024

Heliyon

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“…The prognostic power of TNFRSF4 has already been studied in several cancers, with some contrasting results. Overexpression has been found to be unfavourable in head and neck squamous cell carcinoma [ 36 ], acute myeloid leukaemia (AML) [ 37 ] and hepatocellular carcinoma (HCC) [ 38 ]. While these prognostic trends conflict with the trends observed in our model, several studies have also found that elevated expression of TNFRSF4 and its protein counterpart OX40 as favourable in cancers, including colorectal cancer (CRC) [ 39 , 40 ], cutaneous malignant melanoma [ 41 ] and endometrial carcinoma (EC) [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

In vivo cisplatin-resistant neuroblastoma metastatic model reveals tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as an independent prognostic factor of survival in neuroblastoma

Murphy,

Devis-Jauregui,

Struck

et al. 2024

PLoS ONE

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Neuroblastoma is the most common solid extracranial tumour in children. Despite major advances in available therapies, children with drug-resistant and/or recurrent neuroblastoma have a dismal outlook with 5-year survival rates of less than 20%. Therefore, tackling relapsed tumour biology by developing and characterising clinically relevant models is a priority in finding targetable vulnerability in neuroblastoma. Using matched cisplatin-sensitive KellyLuc and resistant KellyCis83Luc cell lines, we developed a cisplatin-resistant metastatic MYCN-amplified neuroblastoma model. The average number of metastases per mouse was significantly higher in the KellyCis83Luc group than in the KellyLuc group. The vast majority of sites were confirmed as having lymph node metastasis. Their stiffness characteristics of lymph node metastasis values were within the range reported for the patient samples. Targeted transcriptomic profiling of immuno-oncology genes identified tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as a significantly dysregulated MYCN-independent gene. Importantly, differential TNFRSF4 expression was identified in tumour cells rather than lymphocytes. Low TNFRSF4 expression correlated with poor prognostic indicators in neuroblastoma, such as age at diagnosis, stage, and risk stratification and significantly associated with reduced probability of both event-free and overall survival in neuroblastoma. Therefore, TNFRSF4 Low expression is an independent prognostic factor of survival in neuroblastoma.

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“…In this study, we also identified HVEM gene expression as a prognostic factor in ALL patients. Numerous reports have measured the expression of HVEM in acute myeloid leukemia (AML) [53,54]. Gene dysregulation was reported in studies investigating HVEM expression in patients with AML [54].…”

Section: Discussionmentioning

confidence: 99%

Herpesvirus Entry Mediator as an Immune Checkpoint Target and a Potential Prognostic Biomarker in Myeloid and Lymphoid Leukemia

Basingab,

Alzahrani,

Alrofaidi

et al. 2024

Biomolecules

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Herpesvirus entry mediator (HVEM) is a molecular switch that can modulate immune responses against cancer. The significance of HVEM as an immune checkpoint target and a potential prognostic biomarker in malignancies is still controversial. This study aims to determine whether HVEM is an immune checkpoint target with inhibitory effects on anti-tumor CD4+ T cell responses in vitro and whether HVEM gene expression is dysregulated in patients with acute lymphocytic leukemia (ALL). HVEM gene expression in tumor cell lines and peripheral blood mononuclear cells (PBMCs) from ALL patients and healthy controls was measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Tumor cells were left untreated (control) or were treated with an HVEM blocker before co-culturing with CD4+ T cells in vitro in a carboxyfluorescein succinimidyl ester (CFSE)-dependent proliferation assay. HVEM expression was upregulated in the chronic myelogenous leukemia cell line (K562) (FC = 376.3, p = 0.086) compared with normal embryonic kidney cells (Hek293). CD4+ T cell proliferation was significantly increased in the HVEM blocker-treated K562 cells (p = 0.0033). Significant HVEM differences were detected in ALL PBMCs compared with the controls, and these were associated with newly diagnosed ALL (p = 0.0011) and relapsed/refractory (p = 0.0051) B cell ALL (p = 0.0039) patients. A significant differentiation between malignant ALL and the controls was observed in a receiver operating characteristic (ROC) curve analysis with AUC = 0.78 ± 0.092 (p = 0.014). These results indicate that HVEM is an inhibitory molecule that may serve as a target for immunotherapy and a potential ALL biomarker.

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The role of tumor necrosis factor receptor superfamily member 4 (TNFRSF4) gene expression in diagnosis and prognosis of acute myeloid leukemia

Cited by 8 publications

References 42 publications

Prognostic significance of TNFRSF4 expression and development of a pathomics model to predict expression in hepatocellular carcinoma

Prognostic significance of TNFRSF4 expression and development of a pathomics model to predict expression in hepatocellular carcinoma

In vivo cisplatin-resistant neuroblastoma metastatic model reveals tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as an independent prognostic factor of survival in neuroblastoma

Herpesvirus Entry Mediator as an Immune Checkpoint Target and a Potential Prognostic Biomarker in Myeloid and Lymphoid Leukemia

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