Matrix Metalloproteinase-9 Expression by Hodgkin-Reed-Sternberg Cells Is Associated with Reduced Overall Survival in Young Adult Patients with Classical Hodgkin Lymphoma

Campos, Antônio Hugo José Fróes Marques; Vassallo, José; Soares, Fernando Augusto

doi:10.1371/journal.pone.0074793

Cited by 5 publications

(7 citation statements)

References 30 publications

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“…Taken together, this suggests that IL-6 participates in the pathogenesis of HL. The another molecule, MMP9, enriched in the transcriptional misregulation in cancer pathway and was a hub protein in the PPI network in the present study, and has also been previously reported to be associated with reduced overall survival in patients with cHL ( 31 ) through effects on immune system regulation ( 32 ). A previous study has suggested that the patients with aggressive non-Hodgkin lymphoma and MMP9 expression had poor overall survival ( 33 ).…”

Section: Discussionsupporting

confidence: 72%

Identification of key genes and pathways associated with classical Hodgkin lymphoma by bioinformatics analysis

Kuang

Guo

2017

Molecular Medicine Reports

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The current study aimed to explore the mechanisms associated with classic Hodgkin lymphoma (cHL) to identify novel diagnostic and therapeutic targets. The GES12453 microarray dataset was downloaded from the Gene Expression Omnibus database; the differentially expressed genes (DEGs) between cHL samples and normal B cell samples by were identified using the limma package. Gene ontology (GO) and pathway enrichment analysis of DEGs gene were performed. Furthermore, construction and analysis of protein-protein interaction (PPI) network was performed, and co-expression modules of DEGs were produced. A total of 450 DEGs were identified, comprising 216 upregulated and 234 downregulated genes in cHL compared with normal B cell samples. The DEGs were enriched in biological processes associated with immune response. The upregulated genes were mainly associated with the pathway of transcriptional misregulation in cancer, while downregulated genes were associated with B cell receptor signaling. PPI network analysis demonstrated that IL6 had the highest connectivity degree. Interleukin-6 (IL6) and signal transducer and activator of transcription 1 (STAT1) were demonstrated to be involved with the response to cytokine GO term in co-expression module 1. Spleen tyrosine kinase (SYK), B-cell linker protein (BLNK), CD79B, phospholipase C γ2 (PLCG2) were enriched in the B cell receptor signaling pathway in module 2. Matrix metallopeptidase 9 (MMP9), protein tyrosine phosphatase receptor type C had the highest connectivity degrees in module 3 and module 4, respectively. The results suggested that DEGs, including IL6, STAT1, MMP9, SYK, BLNK, PLCG2 and CD79B, and the pathways of B cell receptor signaling, Epstein-Barr virus infection and transcriptional misregulation in cancer have strong potential to be useful as targets for diagnosis or treatment of cHL.

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Section: Discussionsupporting

confidence: 72%

Identification of key genes and pathways associated with classical Hodgkin lymphoma by bioinformatics analysis

Kuang

Guo

2017

Molecular Medicine Reports

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“…Tissue microarrays (TMAs) and immunohistochemistry were done at the A. C. Camargo Cancer Center. The TMAs were built as reported elsewhere 32 . Each case was spotted in duplicate.…”

Section: Methodsmentioning

confidence: 99%

Frequency of EBV associated classical Hodgkin lymphoma decreases over a 54-year period in a Brazilian population

Campos

Moreira

Ribeiro

et al. 2018

Sci Rep

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The epidemiology of classical Hodgkin lymphoma varies significantly in populations with different socioeconomic conditions. Among other changes, improvement in such conditions leads to a reduction in the association with EBV infection and predominance of the nodular sclerosis subtype. This study provides an overview of the epidemiology of 817 cases of classical Hodgkin lymphoma diagnosed in five reference hospitals of the State of Sao Paulo, Brazil, over 54 years (1954–2008). The cases were distributed in 3 periods (1954–1979; 1980–1999; and 2000–2008). EBV-positive cases decreased from 87% to 46%. In children and adolescents (<15 years) and in young adults (15–45 years), EBV-positive cases decreased respectively from 96% to 64%, and from 85% to 32%. The percentage of male patients declined from 80% to 58%. In older patients (>45 years), the decrease in EBV infection was not significant. Nodular Sclerosis was the most common subtype in all periods. These results support the hypothesis that, in the Brazilian State of Sao Paulo, classical Hodgkin lymphoma has changed and now shows characteristics consistent with Pattern III observed in populations that experienced a similar socioeconomic transition.

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“…This relationship could be based on the differences in collagen metabolism in the qPET‐positive cases associated with poorer clinical outcome: an additional investigation revealed that the collagen modulating enzyme MMP9 was more expressed in the cases with an increased proportion of weakly stained fibers than in the cases with fewer such fibers. Increased MMP9 expression correlated with reduced overall survival in 148 young adult cases in one study 7 . Various other works indicated MMP9 as a correlate to collagen alteration in lymphomas 38–40 .…”

Section: Discussionmentioning

confidence: 84%

“…1,2,6 A potential histological parameter-the quantification of MMP9-positive cells-was currently discussed in several publications. [7][8][9] MMP9 is a matrixin belonging to the zinc-metalloproteinases family involved in collagenous degradation of the extracellular matrix. 10 The discovery of a robust and reliable prognostic marker would help especially in the selection of therapy for younger patients.…”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15] For the quantification of histological parameters, convolutional deep learning networks (CNN) have become increasingly important serving as a suitable deep learning architecture for analyzing tissue structures on whole slide images. [16][17][18] Due to MMP9 quantification in classical Hodgkin lymphoma had shown significant prognostic power 7 we hypothesized that picrosirius red collagen staining of Hodgkin's lymphoma tissue might serve as a prognostic signal in young patients. As it was almost impossible to accurately quantify the absolute amount of faintly stained fibers through quantification of the microscopic field of view, we decided to use a deep learning approach with the CNN model YOLOv4 which has been successfully used in several medical computer vision tasks regarding object detection on whole slides.…”

Section: Introductionmentioning

confidence: 99%

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Deep‐learning based classification of a tumor marker for prognosis on Hodgkin's disease

Motmaen

Sereda

Brobeil

et al. 2023

European J of Haematology

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PurposeHodgkin's disease is a common malignant disorder in adolescent patients. Although most patients are cured, approximately 10%–15% of patients experience a relapse or have resistant disease. Furthermore, there are no definitive molecular predictors for early identification of patients at high risk of treatment failure to first line therapy. The aim of this study was to evaluate the deep learning‐based classifier model of medical image classification to predict clinical outcome that may help in appropriate therapeutic decisions.MethodsEighty‐three FFPE biopsy specimens from patients with Hodgkin's disease were stratified according to the patient's qPET scores, stained with picrosirius red dye and digitalized by whole slide image scanning. The resulting whole slide images were cut into tiles and annotated by two classes based on the collagen fibers' degree of coloring with picrosirius red. The neural network (YOLOv4) was then trained with the annotated data. Training was performed with 30 cases. Prognostic power of the weakly stained picrosirius red fibers was evaluated with 53 cases. The same neural network was trained with MMP9 stained tissue slides from the same cases and the quantification results were compared with the variant from the picrosirius red cases.ResultsThere was a weak monotonically increasing relationship by parametric ANOVA between the qPET groups and the percentages of weakly stained fibers (p = .0185). The qPET‐positive cases showed an average of 18% of weakly stained fibers, and the qPET‐negative cases 10%–14%. Detection performance showed an AUC of 0.79.ConclusionsPicrosirius red shows distinct associations as a prognostic metric candidate of disease progression in Hodgkin's disease cases using whole slide images but not sufficiently as a prognostic device.

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Matrix Metalloproteinase-9 Expression by Hodgkin-Reed-Sternberg Cells Is Associated with Reduced Overall Survival in Young Adult Patients with Classical Hodgkin Lymphoma

Cited by 5 publications

References 30 publications

Identification of key genes and pathways associated with classical Hodgkin lymphoma by bioinformatics analysis

Identification of key genes and pathways associated with classical Hodgkin lymphoma by bioinformatics analysis

Frequency of EBV associated classical Hodgkin lymphoma decreases over a 54-year period in a Brazilian population

Deep‐learning based classification of a tumor marker for prognosis on Hodgkin's disease

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