Proliferative, pro-inflammatory, and angiogenesis regulator gene expression profile defines prognosis in different histopathological subtypes of nodal peripheral T-cell lymphoma

Lage, Luís Alberto de Pádua Covas; Levy, Débora; Xavier, Flávia Caló Aquino; Reis, Diego dos Santos; Costa, Renata de Oliveira; Gonçalves, Marianne Castro; Rocha, Vanderson; Zerbini, Maria Cláudia Nogueira; Pereira, Juliana

doi:10.18632/oncotarget.27098

Cited by 7 publications

(2 citation statements)

References 43 publications

(51 reference statements)

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“…The first subgroup of cells (clusters 3, 5, 7, and 8) was highly proliferative and was labeled with MKI67 , [25] TOP2A , [26] and CDK1 genes [27] . According to GO and KEGG analysis of the DEGs in every cluster, this group of cells could be further divided into 2 subgroups.…”

Section: Resultsmentioning

confidence: 99%

Single-cell transcriptional profiling reveals the heterogeneity in embryonal rhabdomyosarcoma

Hong

Xia

et al. 2021

Medicine

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Rhabdomyosarcoma is the most common soft tissue sarcoma in children, and embryonal rhabdomyosarcoma is the most typical type of rhabdomyosarcoma. The heterogeneity, etiology, and origin of embryonal rhabdomyosarcoma remain unknown.After obtaining the gene expression data of every cell in the tumor tissue by single-cell RNA sequencing, we used the Seurat package in R studio for quality control, analysis, and exploration of the data. All cells are divided into tumor cells and non-tumor cells, and we chose tumor cells by marker genes. Then, we repeated the process to cluster the tumor cells and divided the subgroups by their differentially expressed genes and gene ontology/Kyoto Encyclopedia of Genes and Genomes analysis. Additionally, Monocle 2 was used for pseudo-time analysis to obtain the evolution trajectory of cells in tumor tissues.Tumor cells were divided into 5 subgroups according to their functions, which were characterized by high proliferation, sensing and adaptation to oxygen availability, enhanced epigenetic modification, enhanced nucleoside phosphonic acid metabolism, and ossification. Evolution trajectory of cells in tumor tissues is obtained.We used pseudo-time analysis to distinguish between mesenchymal stem cells and fibroblasts, proved that embryonal rhabdomyosarcoma in the pelvic originated from skeletal muscle progenitor cells, showed the evolutionary trajectory of embryonal rhabdomyosarcoma, and improved the method of evaluating the degree of malignancy of embryonal rhabdomyosarcoma.

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Section: Resultsmentioning

confidence: 99%

Single-cell transcriptional profiling reveals the heterogeneity in embryonal rhabdomyosarcoma

Hong

Xia

et al. 2021

Medicine

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“…We previously demonstrated that overexpression of CCNA2 gene and CHECK1 protein were associated with poor prognosis in nPTCLs [12]. Here, we aimed to test and confirm the hypothesis that GATA3 gene expression would be associated with overall survival and progression-free survival and could be used as a marker to differentiate histopathological subtypes of nPTCLs.…”

Section: Introductionmentioning

confidence: 89%

<strong><em>GATA 3</em> Gene Overexpression Is A Biomarker of Adverse Prognosis for Peripheral T-Cell Lymphoma, Not Otherwise Specified and for ALK-Negative Anaplastic Large Cell Lymphoma: An Exploratory Analysis of 80 Latin American Cases of nodal PTCLs</strong>

Lage¹,

Brito²,

Levy³

et al. 2020

Preprint

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Background: Nodal peripheral T-cell lymphomas (nPTCLs) encompass a heterogeneous group of mature and aggressive lymphoid malignancies, including peripheral T-cell lymphoma, not otherwise specified (PTCL/NOS), angioimmunoblastic T-cell lymphoma (AITL) and anaplastic large cell lymphoma (ALCL) ALK-positive and ALK-negative. Their differential diagnosis and prognosis are an issue in the clinical practice. Accurate biomarkers to refine the different subtypes of nPTCLs and to stratify their prognosis are essential to improve their treatment approach. The aim of this study was to test the prognostic impact of GATA3 gene expression, and its capability to discriminate the different subtypes of nPTCLs. Patients and Methods: From 2000 to 2017, 80 patients with nPTCLs were eligible for GATA3 gene expression analysis that was assessed retrospectively by quantitative real time PCR (qRT-PCR) of neoplastic biopsies in Formalin-Fixed Paraffin-Embedded samples (FFPE). Results: Median age was 49 years old (IqR 34-59), 43/80 (53.7%) were male. Median follow-up was 1.72 years. Of them, 36.3% were classified as PTCL/NOS, 31.2% ALK-negative ALCL, 21.2% ALK-positive ALCL and 11.3% AITL. The majority of cases had advanced stage (III/IV). Two-year estimated overall survival (OS) and progression-free survival (PFS) were 52.2% and 39.5%, respectively. The median GATA3 gene expression level was 0.49% (range 0 – 7.07) in all cohort, it was 0.11% for ALK-positive ALCL, 0.46% for ALK-negative ALCL, 0.86% for PTCL/NOS and 0.67% for AITL. The difference of GATA3 gene expression among distinct variants of nPTCLs was statistically significant (p < 0.001). GATA3 gene expression levels ≥ 0.71% discriminate PTCL/NOS from ALK-negative ALCL and AITL with sensitivity of 62% and specificity of 80.3%. GATA3 gene expression levels ≥ median was associated with poor 2-year OS for PTCL/NOS (46.7% x 21.4%, p=0.04) and for ALK-negative ALCL (85.7% x 54.5%, p=0.04). Conclusion: Despite the relative small and heterogeneous group of patients with nPTCLs, GATA3 gene overexpression may be an important biomarker associated with poor prognosis in PTCL/NOS and ALK-negative ALCL. Moreover it may also discriminate different subtypes of nPTCLs. Further studies with larger series of patients should confirm our findings.

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Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen–Results of a Real-Life Study From a Middle-Income Country

Lage

Brito

Barreto

et al. 2022

Clinical Lymphoma Myeloma and Leukemia

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Proliferative, pro-inflammatory, and angiogenesis regulator gene expression profile defines prognosis in different histopathological subtypes of nodal peripheral T-cell lymphoma

Cited by 7 publications

References 43 publications

Single-cell transcriptional profiling reveals the heterogeneity in embryonal rhabdomyosarcoma

Single-cell transcriptional profiling reveals the heterogeneity in embryonal rhabdomyosarcoma

<strong><em>GATA 3</em> Gene Overexpression Is A Biomarker of Adverse Prognosis for Peripheral T-Cell Lymphoma, Not Otherwise Specified and for ALK-Negative Anaplastic Large Cell Lymphoma: An Exploratory Analysis of 80 Latin American Cases of nodal PTCLs</strong>

Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen–Results of a Real-Life Study From a Middle-Income Country

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