Low miR200b-5p levels in minor salivary glands: a novel molecular marker predicting lymphoma development in patients with Sjögren’s syndrome

Kapsogeorgou, Efstathia K.; Papageorgiou, Alexia; Protogerou, Athanase D.; Voulgarelis, Michael; Tzioufas, Athanasios G.

doi:10.1136/annrheumdis-2017-212639

Cited by 24 publications

(27 citation statements)

References 31 publications

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“…Therefore, it is not surprising that mir142 was highly expressed in highly infiltrating TMEs . Moreover, miR‐223, mir155, mir187, and mir200b have also been reported to be associated with the immune response, so it will be worthwhile to conduct more research exploring the relationships between noncoding RNAs and the immune response in the future.…”

Section: Discussionmentioning

confidence: 99%

An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle‐invasive bladder cancer (MIBC)

et al. 2020

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Immune checkpoint inhibitors (ICIs) are novel treatments that significantly improve the survival time of MIBC patients, but immunotherapeutic responses are different among MIBC patients. Therefore, it is urgent to find predictive biomarkers that can accurately identify MIBC patients who are sensitive to ICIs. In this study, we computed the relative abundances of 24 immune cells based on the expression profiles of MIBC patients using single-sample gene set enrichment analysis (ssGSEA).Unsupervised clustering analysis of the 24 immune cells was performed to classify MIBC patients into different immune-infiltrating groups. Genome (gene mutation and copy number variation), transcriptome (mRNA, lncRNA, and miRNA), and functional enrichment were found to be heterogeneous among different immune-infiltrating groups. We identified 282 differentially expressed genes (DEGs) associated with immune infiltration by comparing the expression profiles of patients with different immune infiltration profiles, and 20 core prognostic DEGs were identified by univariate Cox regression analysis. An immune-relevant gene signature (TIM signature) consisting of nine key prognostic DEGs (CCDC80, CD3D, CIITA, FN1, GBP4, GNLY, SPINK1, UBD, and VIM) was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Receiver operating characteristic (ROC) curves and subgroup analysis confirmed that the TIM signature was an ideal biomarker for predicting the prognosis of MIBC patients. Its value in predicting immunotherapeutic responses was also validated in The Cancer Genome Atlas (TCGA) cohort (AUC = 0.69, 95% CI = 0.63-0.74) and the IMvigor210 cohort (AUC = 0.64, 95% = 0.55-0.74). The TIM signature demonstrates a powerful ability to distinguish MIBC patients with different prognoses and immunotherapeutic responses, but more prospective studies are needed to assess its reliability in the future. K E Y W O R D S gene expression, immune infiltration, immunotherapeutic response, muscle-invasive bladder cancer (MIBC), prognosis | 2775 JIANG et Al.

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Section: Discussionmentioning

confidence: 99%

An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle‐invasive bladder cancer (MIBC)

et al. 2020

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“…miRNA200b-5p and thymic stromal lymphopoietin (TSLP) [89,90]. In a very recent paper [91], low miRNA200b-5p was reduced in prelymphoma and lymphoma pSS patients, proving to be a useful predictor. TSLP increases in the serum of pSS patients, with higher levels in the myoepithelial sialadenitis and mixed cryoglobulinemia, and with the highest level in patients with B-cell lymphoma [92].…”

Section: Laboratory Biomarkers Will Be Crucial To Improve Lymphoma Prmentioning

confidence: 99%

Predicting lymphoma development in patients with Sjögren’s syndrome

Vita

Gandolfo

2019

Expert Review of Clinical Immunology

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Introduction: The issue of predicting lymphoma in primary Sjögren's syndrome (pSS) starts from its clinical and biologic essence, i.e., an autoimmune exocrinopathy with sicca syndrome, inflammation and lymphoproliferation of MALT (mucosa-associated lymphoid tissue) in exocrine glands. Areas covered: The two major predictors to be firstly focused are persistent salivary gland (SG) swelling and cryoglobulinemic vasculitis with related features as purpura and low C4, or the sole serum cryoglobulinemia repeatedly detected. They are pathogenetically linked and reflect a heavier MALT involvement by histopathology, with the expansion of peculiar rheumatoid factor (RF)-positive clones/ idiotypes. Other predictors include lymphadenopathy, splenomegaly, neutropenia, lymphopenia, serum beta2-microglobulin, monoclonal immunoglobulins, light chains, and RF. Composite indexes/scores may also predict lymphoma. Expert opinion: Prediction at baseline needs amelioration, and must be repeated in the follow-up. Careful clinical characterization, with harmonization and stratification of large cohorts, is a relevant preliminary step. Validated and new biomarkers are needed in biologic fluids and tissues. SG echography with automatic scoring could represent a future imaging biomarker, still lacking. Scoring MALT involvement in pSS, as an additional tool to evaluate disease activity and possibly to predict lymphoma, is welcomed. All these efforts are now ongoing within the HarmonicSS project and in other research initiatives in pSS.

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“…Significantly lower levels of miR200b‐5p, a miRNA which regulates expression of autoantibodies directed to intracellular autoantigens, La/SSB, were characterized in SS patients with MALT lymphoma compared with those without ( p < 0.05; Gourzi, Kapsogeorgou, Kyriakidis, & Tzioufas, ). Similarly, in the study of Kapsogeorgou, Papageorgiou, Protogerou, Voulgarelis, and Tzioufas (), miR200b‐5p was significantly downregulated in patients with SS who would develop or had NHL, and was able to discriminate this subset ( p < 0.0001) from those without lymphoma or those with non‐SS sialadenitis. These investigators reported miR200b‐5p as a strong independent predictor of patients who would develop NHL.…”

Section: Resultsmentioning

confidence: 78%

“…Significantly lower levels of miR200b-5p, a miRNA which regulates expression of autoantibodies directed to intracellular autoantigens, La/ SSB, were characterized in SS patients with MALT lymphoma compared with those without (p < 0.05; Gourzi, Kapsogeorgou, Kyriakidis, & Tzioufas, 2015). Similarly, in the study of Kapsogeorgou, Papageorgiou, Protogerou, Voulgarelis, and Tzioufas (2018) Barone et al (2008) reported that CXCL12 was principally detected in infiltrated ducts and malignant B cells in the salivary glands of patients with SS. Additionally, CXCL12 levels were increased in MALT lymphomas and isolated tumor cells, suggesting the direct involvement of CXCL12 in the organization of ectopic reactive lymphoid tissue and its association with the malignant B-cell component and regulation of malignant B-cell survival.…”

Section: Geneticsmentioning

confidence: 94%

World Workshop on Oral Medicine VII: Biomarkers predicting lymphoma in the salivary glands of patients with Sjögren’s syndrome—A systematic review

et al. 2019

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Objective To conduct a systematic review of studies exploring potential biomarkers for development, course, and efficacy of treatment of lymphomas in salivary glands of patients with Sjögren's syndrome. Material and Methods Eligible studies were identified through a comprehensive search of two databases, that is, PubMed and EMBASE. Quality of included articles was assessed with the “Quality In Prognosis Studies” (QUIPS) tool. The “CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies” (CHARMS) was used to facilitate data extraction. Results Fifty‐eight studies met the inclusion criteria. Only one study assessed the progression of lymphoma. Moderate risk of bias was detected in “outcome measurement,” “study participation,” and “study confounding” domains. Parotid gland enlargement, mixed monoclonal cryoglobulins, and low C4 levels represented strongest predictors of lymphoma development. The role of histological biomarkers, and specifically germinal centers, remains controversial. Clinical and methodological heterogeneity across studies precluded conduct of a meta‐analysis. Conclusions Specific biomarkers in combination with clinical manifestations represent potential candidates for advancing precision medicine approaches to lymphoma prediction in patients with Sjögren's syndrome. Current focus has increasingly been on genetic and epigenetic markers as candidate predictors. Predictive accuracy of key biomarker candidates remains to be tested in well‐designed prospectively followed Sjögren's syndrome cohorts.

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Low miR200b-5p levels in minor salivary glands: a novel molecular marker predicting lymphoma development in patients with Sjögren’s syndrome

Abstract: These findings support that miR200b-5p levels in MSGs represent a novel predictive and possibly pathogenetic mechanism-related factor for the development of SS-associated NHL, since its expression is impaired years before lymphoma clinical onset.

Cited by 24 publications

References 31 publications

An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle‐invasive bladder cancer (MIBC)

An immune relevant signature for predicting prognoses and immunotherapeutic responses in patients with muscle‐invasive bladder cancer (MIBC)

Predicting lymphoma development in patients with Sjögren’s syndrome

World Workshop on Oral Medicine VII: Biomarkers predicting lymphoma in the salivary glands of patients with Sjögren’s syndrome—A systematic review

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