Integrin alpha 10, CD44, PTEN, cadherin-11 and lactoferrin expressions are potential biomarkers for selecting patients in need of central nervous system prophylaxis in diffuse large B-cell lymphoma

Lemma, Siria; Kuusisto, Milla E.L.; Haapasaari, Kirsi‐Maria; Sormunen, Raija; Lehtinen, Tuula; Klaavuniemi, Tuula; Eray, Mine; Jantunen, Esa; Soini, Ylermi; Vasala, Kaija; Böhm, Jan; Salokorpi, Niina; Koivunen, Petri; Karihtala, Peeter; Vuoristo, Jussi; Turpeenniemi‐Hujanen, Taina; Kuittinen, Outi

doi:10.1093/carcin/bgx061

Cited by 21 publications

(18 citation statements)

References 47 publications

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“…Interestingly, these three hub genes are also enriched in measles; thus, it is important that further research be conducted in this arena. In a previous study, CD44 expression was associated with the non-GC phenotype and should therefore be studied as a promising candidate for biological marker screening in systemic DLBCL patients [ 32 ]. The high expression of CFLAR in the ABC subtype may facilitate cell proliferation and reduce TRAIL-induced apoptosis [ 33 ]; this previous hypothesis was verified in our analysis by the enrichment of CFLAR in the regulation of satellite cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes and Key Pathways Associated with Two Subtypes of Diffuse Large B-Cell Lymphoma Based on Gene Expression Profiling via Integrated Bioinformatics

Liu

Meng

et al. 2018

BioMed Research International

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There is a significant difference in prognosis between the germinal center B-cell (GCB) and activated B-cell (ABC) subtypes of diffuse large B-cell lymphoma (DLBCL). However, the signaling pathways and driver genes involved in these disparate subtypes are ambiguous. This study integrated three cohort profile datasets, including 250 GCB samples and 250 ABC samples, to elucidate potential candidate hub genes and key pathways involved in these two subtypes. Differentially expressed genes (DEGs) were identified. After Gene Ontology functional enrichment analysis of the DEGs, protein-protein interaction (PPI) network and sub-PPI network analyses were conducted using the STRING database and Cytoscape software. Subsequently, the Oncomine database and the cBioportal online tool were employed to verify the alterations and differential expression of the 8 hub genes (MME, CD44, IRF4, STAT3, IL2RA, ETV6, CCND2, and CFLAR). Gene set enrichment analysis was also employed to identify the intersection of the key pathways (JAK-STAT, FOXO, and NF-κB pathways) validated in the above analyses. These hub genes and key pathways could improve our understanding of the process of tumorigenesis and the underlying molecular events and may be therapeutic targets for the precise treatment of these two subtypes with different prognoses.

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Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes and Key Pathways Associated with Two Subtypes of Diffuse Large B-Cell Lymphoma Based on Gene Expression Profiling via Integrated Bioinformatics

Liu

Meng

et al. 2018

BioMed Research International

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“…53 Additional biomarkers emerging from pathological analyses have been utilized to stratify risk, including ITGA10, CXCR5 and nuclear PTEN. 54,55 Further research in these areas in concert with existing biomarkers and clinical risk stratification tools should be performed to determine the clinical utility of these studies before they are incorporated into routine clinical care.…”

Section: Evaluating Risk Of Central Nervous System Recurrencementioning

confidence: 99%

Advances in risk assessment and prophylaxis for central nervous system relapse in diffuse large B-cell lymphoma

Qualls

Abramson

2018

Haematologica

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Central nervous sytem recurrence of diffuse large B-cell lymphoma is an uncommon but devastating event, making identification of patients at high risk for relapse within the central nervous system essential for clinicians. Modern risk stratification includes both clinical and biological features. A validated clinical risk model employing the five traditional International Prognostic Index risk factors plus renal or adrenal involvement can identify a high-risk patient population with a central nervous system recurrence risk of greater than 10%. Lymphoma involvement of certain discrete extranodal sites such as the testis also confers increased risk, even in stage I disease. Adverse biological risk factors for central nervous system relapse include presence of translocations of MYC, BCL2 and/or BCL6, in so-called double- or triple-hit lymphoma. Immunohistochemically detectable co-expression of MYC and BCL2 in the absence of translocations also portends an increased risk of relapse within the central nervous system, particularly in the setting of the activated B-cell-like subtype of diffuse large B-cell lymphoma. The role, method, and timing of prophylactic therapy remain controversial based on the available data. We review both intrathecal and systemic strategies for prophylaxis in high-risk patients. Our preference is for systemic methotrexate in concert with standard chemoimmunotherapy in the majority of cases. Several novel agents have also demonstrated clinical activity in primary and secondary central nervous system lymphoma and warrant future investigation in the prophylactic setting.

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“…Other studies revealed that ITGA2 was expressed in gastric cancer (51), pancreatic cancer (52) and pancreatic ductal adenocarcinoma (PDAC) (53). In addition, ITGA10 was expressed in B-cell lymphoma (54) and ITGA11 was expressed in breast cancer (55), lung squamous cancer (56) and neck squamous cell carcinoma (57).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic and prognostic values of integrin α subfamily mRNA expression in colon adenocarcinoma

et al. 2019

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The integrin α ( ITGA ) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in colon adenocarcinoma (COAD) remain elusive. The present study investigated the significance of the expression of ITGA genes in COAD from the perspective of diagnosis and prognosis. A COAD RNA-sequencing dataset was obtained from The Cancer Genome Atlas. The present study investigated the biological function of the ITGA subfamily genes through bioinformatics analysis. Reverse transcription-quantitative polymerase chain reaction was applied to investigate the distribution of integrin α8 ( ITGA8 ) expression in COAD tumors and adjacent normal tissues. Bioinformatics analysis indicated that ITGA genes were noticeably enriched in cell adhesion and the integrin-mediated signaling pathway, and co-expressed with each other. It was also revealed through observation that the majority of gene expression was significantly low in tumor tissues (P<0.05), and diagnostic receiver operating characteristic curves revealed that most of the genes could serve as significant diagnostic markers in COAD (P<0.05), especially ITGA8 which had a high diagnostic value with an area under curve (AUC) of 0.989 [95% confidence interval (CI) 0.980–0.997] in COAD (P<0.0001). In addition, ITGA8 expression was verified in clinical samples and it was revealed that it was higher in adjacent normal tissues (P=0.041) compared to COAD tissues, and the AUC was 0.704 (95% CI, 0.577–0.831; P<0.0085). Multivariate survival analysis indicated that integrin α ( ITGA5 ) may be an independent prognostic indicator for COAD overall survival. Gene set enrichment analysis indicated that ITGA5 may participate in multiple biological processes and pathways. The present study revealed that ITGA genes were associated with the diagnosis and prognosis of COAD. The mRNA expression of ITGA8 may be a potential diagnosis biomarker and ITGA5 may serve as an independent prognosis indicator for COAD.

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Integrin alpha 10, CD44, PTEN, cadherin-11 and lactoferrin expressions are potential biomarkers for selecting patients in need of central nervous system prophylaxis in diffuse large B-cell lymphoma

Abstract: SummaryIn this work, we have studied the biology behind DLBCL central nervous system (CNS) tropism and potential biomarkers for CNS relapse prediction. We show that ITGA10, PTEN, CD44, cadherin-11 and lactoferrin levels are altered in CNS lymphomas.

Cited by 21 publications

References 47 publications

Identification of Hub Genes and Key Pathways Associated with Two Subtypes of Diffuse Large B-Cell Lymphoma Based on Gene Expression Profiling via Integrated Bioinformatics

Identification of Hub Genes and Key Pathways Associated with Two Subtypes of Diffuse Large B-Cell Lymphoma Based on Gene Expression Profiling via Integrated Bioinformatics

Advances in risk assessment and prophylaxis for central nervous system relapse in diffuse large B-cell lymphoma

Diagnostic and prognostic values of integrin α subfamily mRNA expression in colon adenocarcinoma

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