1q23.1 homozygous deletion and downregulation of Fc receptor-like family genes confer poor prognosis in chronic lymphocytic leukemia

Daniele, Giulia; L’Abbate, Alberto; Turchiano, Antonella; Palumbo, Orazio; Carella, Massimo; Cunsolo, Crocifissa Lo; Iuzzolino, P.; Lonoce, Angelo; Hernández‐Sánchez, María; Minoia, Carla; Leone, Patrizia; Hernández-Rivas, Jesús María; Storlazzi, Clelia Tiziana

doi:10.1007/s10238-019-00551-0

Cited by 4 publications

(4 citation statements)

References 24 publications

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“…In our study CD20 was associated with prognosis (p = 0.011) and the correlation with FCRLA was good (r s > 0.5). A down-regulation of FCRL genes family confers poor prognosis in chronic lymphocytic leukemia 41 , as in our cases. In the studied cohort, none of the patients were treated with immunotherapy regimens, thus we could not speculate on any predictive role of FCRLA towards therapy response.…”

Section: Discussionsupporting

confidence: 75%

A role for the immune system in advanced laryngeal cancer

Tagliabue

Maffini

Fumagalli

et al. 2020

Sci Rep

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To investigate the role of the altered activation of the immune system in the prognosis of patients affected by laryngeal squamous cell carcinoma (LSCC). We analyzed 56 patients with advanced LSCC divided into two groups according to their prognosis: the first group relapsed within 24 months after treatment, the second group had no evidence of disease at 2 years. The presence of stromal tumor infiltrating lymphocytes (TILs) at the tumor-host border was investigated. In 43 patients we evaluated the expression of 395 genes related to immune system activation through a next generation sequencing panel. Priority-LASSO models and clustering analyses were integrated with multivariate Cox proportional hazard modeling to identify independent genes associated with relapse and estimate hazard ratios in relation to gene expression and TILs. TILs and the expression of genes related with immune system activation (FCGR1A, IFNA17, FCRLA, NCR3, KREMEN1, CD14, CD3G, CD19, CD20 and CD79A) were significantly associated with prognostic factors or disease specific survival. In patients with lymph node metastases and advanced T stage (pT4), the expression of other genes was altered. Low TILs count was highly associated with relapse within 2 years (p < 0.001). Low TILs and altered expression of specific genes associated with tumor-immune systems interactions emerged as independent risk factors, associated to poor prognosis and relapse within 2 years in advanced LSCC. Evaluation of patients’ immune profile could be useful for prognosis and future therapeutic approaches towards personalized therapy.

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Section: Discussionsupporting

confidence: 75%

A role for the immune system in advanced laryngeal cancer

Tagliabue

Maffini

Fumagalli

et al. 2020

Sci Rep

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“…FCRL3, encoding Fc receptor-like protein 3, is reported to be highly expressed in M-CLL instead of U-CLL [43], which demonstrates the inhibitory potential on BCR signaling [44]. And deletion or downregulation of FCRL3 predicts poor prognosis for CLL patients [45]. For the 'black' module, ORA according to KEGG database, demonstrated the NF-kappaB, HIF-1 and AMPK signaling pathways were enriched for the 'black' module.…”

Section: Discussionmentioning

confidence: 99%

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia

Guo

Gao

et al. 2021

J Transl Med

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Background IGHV mutation status is a crucial prognostic biomarker for CLL. In the present study, we investigated the transcriptomic signatures associating with IGHV mutation status and CLL prognosis. Methods The co-expression modules and hub genes correlating with IGHV status, were identified using the GSE28654, by ‘WGCNA’ package and R software (version 4.0.2). The over-representation analysis was performed to reveal enriched cell pathways for genes of correlating modules. Then 9 external cohorts were used to validate the correlation of hub genes expression with IGHV status or clinical features (treatment response, transformation to Richter syndrome, etc.). Moreover, to elucidate the significance of hub genes on disease course and prognosis of CLL patients, the Kaplan–Meier analysis for the OS and TTFT of were performed between subgroups dichotomized by the median expression value of individual hub genes. Results 2 co-expression modules and 9 hub genes ((FCRL1/FCRL2/HELQ/EGR3LPL/LDOC1/ZNF667/SOWAHC/SEPTIN10) correlating with IGHV status were identified by WGCNA, and validated by external datasets. The modules were found to be enriched in NF-kappaB, HIF-1 and other important pathways, involving cell proliferation and apoptosis. The expression of hub genes was revealed to be significantly different, not only between CLL and normal B cell, but also between various types of lymphoid neoplasms. HELQ expression was found to be related with response of immunochemotherapy treatment significantly (p = 0.0413), while HELQ and ZNF667 were expressed differently between stable CLL and Richter syndrome patients (p < 0.0001 and p = 0.0278, respectively). By survival analysis of subgroups, EGR3 expression was indicated to be significantly associated with TTFT by 2 independent cohorts (GSE39671, p = 0.0311; GSE22762, p = 0.0135). While the expression of HELQ and EGR3 was found to be associated with OS (p = 0.0291 and 0.0114 respectively).The Kras, Hedgehog and IL6-JAK-STAT3 pathways were found to be associating with the expression of hub genes, resulting from GSEA. Conclusions The expression of HELQ and EGR3 were correlated with IGHV mutation status in CLL patients. Additionally, the expression of HELQ/EGR3 were prognostic markers for CLL associating with targetable cell signaling pathways.

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“…In particular, the protein encoded by the FCRL2 gene has four extracellular C2-type immunoglobulin domains, a transmembrane domain, and a cytoplasmic domain that contains one immunoreceptor-tyrosine activation motif and two immunoreceptor-tyrosine inhibitory motifs. FCRL2 expression was previously reported as a prognostic factor in chronic lymphocytic leukemia [41, 42].…”

Section: Discussionmentioning

confidence: 99%

Survival correlation of immune response in human cancers

Liu

2019

Oncotarget

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Background: The clinical benefit of immune response is largely unknown. We systematically explored the correlation of immune response with patient outcome in human cancers.Results: The global immune gene signature was primarily located on the plasma membrane with a high gene density at 6p21 and 1q23-1q24. Immune responses varied with a wide range in human cancers. A total of 11 cancer types exhibited significant correlation of immune response with overall survival. Higher immune response was significantly associated with longer overall survival in 7 types and with shorter overall survival in 4 types. In addition, 11 cancer types exhibited significant correlation of immune response with progression-free interval. Higher immune response was significantly associated with longer progression-free interval in 7 types and with shorter progression-free interval in 4 types.Methods: The Ingenuity Knowledge Base and human genome assembly GRCh38 were used to annotate the immune gene signature by cellular components and genomic coordinates, respectively. We devised an mRNA-based metric of pre-existing immune conditions by using the gene signature, and calculated the metric for 10,062 The Cancer Genome Atlas tumor samples across 32 different cancer types. The Kaplan-Meier method was used to evaluate the overall survival and progression-free interval differences between dichotomic groups stratified by the median metric for each cancer type.Conclusions: Immune responses have different impacts on patient outcome in different human cancers. Prospective verification is needed before the findings can be applied for clinical trial development.

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1q23.1 homozygous deletion and downregulation of Fc receptor-like family genes confer poor prognosis in chronic lymphocytic leukemia

Cited by 4 publications

References 24 publications

A role for the immune system in advanced laryngeal cancer

A role for the immune system in advanced laryngeal cancer

HELQ and EGR3 expression correlate with IGHV mutation status and prognosis in chronic lymphocytic leukemia

Survival correlation of immune response in human cancers

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