RESUMEN
BACKGROUND: MiRNAs that are potential biomarkers for predicting prognosis for acute myeloid leukemia (AML) have been identified. However, comprehensive analyses investigating the association between miRNA expression profiles and AML survival remain relatively deficient. METHOD: In the present study, we performed multivariate Cox's analysis and principal component analysis (PCA) using data from The Cancer Genome Atlas (TCGA) to identify potential molecular signatures for predicting non-M3 AML prognosis. RESULT: We found that patients who were still living were significantly younger at diagnosis than those who had died (P = 0.001). In addition, there was a marked difference in living status among different risk category groups (P = 0.022). A multivariate Cox model suggested that three miRNAs were potential biomarkers of non-M3 AML prognosis, including miR-181a-2, miR-25 and miR-362. Subsequently, PCA analyses were conducted to comprehensively represent the expression levels of these three miRNAs in each patient with a PCA value. According to the log-rank test, AML outcome for patients with lower PCA values was significantly different from those with higher PCA values (P < 0.001). Further bioinformatic analysis revealed the biological functions of the selected miRNAs. CONCLUSION: We conducted a comprehensive analysis of TCGA non-M3 AML data, identifying three miRNAs that are significantly correlated with AML survival. PCA values for the identified miRNAs are valuable for predicting AML prognosis.
Asunto(s)
Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , MicroARNs/genética , Adulto , Anciano , Biomarcadores de Tumor/genética , Bases de Datos Genéticas , Femenino , Expresión Génica , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Análisis de Componente Principal , Pronóstico , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
BACKGROUND/AIMS: Y+LAT1 protein, encoded by the SLC7A7 gene (a member of the SLC7 family), forms the cationic amino acid transport system y+L (system y+L). This system transports cationic amino acids such as arginine and lysine out of the cell. Arginine, in particular, is critical for T-cell activation and function in the immune response. METHODS: We analyzed the role of the SLC7A7 gene in the cellular activities of Jurkat cells, specifically the cell cycle and cell proliferation, apoptosis, migration, and invasion. Cell proliferation was assessed using the Cell Counting Kit-8. Apoptosis and the cell cycle were determined with a FACSCalibur flow cytometer. A Transwell chamber was used to measure cell invasion and migration. RESULTS: The proliferative ability of Jurkat cells was not significantly altered by transfection with SLC7A7 overexpression vectors. However, SLC7A7 overexpression significantly decreased the percentage of apoptotic Jurkat cells (P = 0.007) but significantly increased the proportion of G1 phase cells (P = 0.029) and cell migration (P < 0.001) and invasion (P < 0.001). Knockdown of SLC7A7 increased the cell apoptosis rate (P = 0.006) but decreased the G1 phase ratio (P = 0.002) and cell migration (P < 0.001) and invasion (P < 0.001). CONCLUSIONS: SLC7A7 plays a significant role in the pathogenesis of T-cell acute lymphoblastic leukemia.
Asunto(s)
Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Adolescente , Sistema de Transporte de Aminoácidos y+L , Apoptosis , Arginina/análisis , Médula Ósea/metabolismo , Médula Ósea/patología , Movimiento Celular , Proliferación Celular , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/antagonistas & inhibidores , Cadenas Ligeras de la Proteína-1 Reguladora de Fusión/genética , Puntos de Control de la Fase G1 del Ciclo Celular , Humanos , Lactante , Células Jurkat , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Current procedures for diagnosis and biomarker examination of colorectal cancer (CRC) are invasive and unpleasant. There is a great need to identify sensitive and specific biomarkers for early diagnosis of CRC. Circulating microRNAs (miRNAs) are promising molecular markers for CRC prediction. We performed a comprehensive meta-analysis to integrate an evaluation index for diagnostic accuracy of circulating miRNAs in diagnosing CRC patients. Furthermore, we conducted an independent validation set of 49 CRC patients and 49 healthy controls. In our meta-analysis, we found that miR-21 yielded a pooled area under ROC curve (AUC) of 0.867 (sensitivity: 76%, specificity: 82%) in discriminating CRC from controls, and miR-92a yielded a summary AUC of 0.803 (sensitivity: 77%, specificity: 68%); miR-21 had a higher diagnostic efficiency than miR-92a. In the further validation, plasma miR-21 levels in CRC patients were significantly higher than levels observed in healthy subjects. A ROC curve analysis showed a consistent result. However, this phenotype was not present in miR-92a. Moreover, the expression trend of miR-21 in plasma samples was in line with that of tissue samples, along with the cellular level. Current evidences suggest that plasma miR-21 could be a reliable and non-invasive biomarker for CRC diagnosis. Studies with larger cohorts that include the diagnostic value of plasma miR-21 for CRC are warranted.
Asunto(s)
Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/diagnóstico , MicroARNs/sangre , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Estudios de Casos y Controles , Neoplasias Colorrectales/genética , Diagnóstico Precoz , Femenino , Humanos , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Curva ROC , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PURPOSE: Leukemia-associated fusion genes are closely related to the occurrence, development, diagnosis, and treatment of leukemia. DNA microarrays and second-generation sequencing have discovered multiple B-ALL fusion genes. We identified a novel MEF2C::SS18L1 fusion gene in a child diagnosed with B-ALL. This study investigates the oncogenicity and prognosis of this fusion gene in B-ALL. METHODS: A child with B-ALL who has a MEF2C::SS18L1 fusion is reported as a newly discovered case. Compared the breakpoints, structural domains, clinical phenotypes, and differential expression genes of MEF2C::SS18L1 and MEF2D::SS18.Using "ONCOFUSE" software, the carcinogenicity of MEF2C::SS18L1 is predicted. Using whole transcriptome sequencing, we analyze the breakpoints and the secondary structure of the fusion protein. Further, we compared the structures, differentially expressed genes, and clinical phenotypes of MEF2D and MEF2C fusion genes by DESeq, GO functional enrichment, and flow cytometry immunophenotyping analysis. RESULTS: Whole transcriptome sequencing identified a MEF2C::SS18L1 fusion transcript in a 3-year-old child with B-ALL. The MADS box, MEF structural domain, HJURP_C structural domain, and TAD I structural domain of MEF2C, and the QPGY structural domain of SS18L1, make up the fusion protein. "Oncofuse" found a 0.99 Bayesian probability that the fusion gene drives cancer. The breakpoint positions, fusion protein secondary structures, differentially expressed genes, and clinical characteristics of this patient were identical to those with MEF2D::SS18 fusion gene. CONCLUSION: We identified a novel MEF2C::SS18L1 fusion gene in childhood ALL, which shares similar structural and clinical characteristics with MEF2D::SS18. Further studies with more samples should be conducted in future.
Asunto(s)
Factores de Transcripción MEF2 , Proteínas de Fusión Oncogénica , Niño , Preescolar , Femenino , Humanos , Masculino , Factores de Transcripción MEF2/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genéticaRESUMEN
Background: The Epstein-Barr virus-associated natural killer (NK) and T-cell lymphoma (EBV + NK/T cell lymphoma) is a severe illness mainly affecting children and young adults, often resulting in a poor prognosis. To date, there is no consensus on an established treatment strategy. This study aims to evaluate the efficacy and safety of the mSMILE (modified steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy regimen in treating EBV+ NK/T-cell lymphoma and to provide insights into potential treatment outcomes. Methods: In this study, we conducted a retrospective analysis of the clinical data and treatment outcomes for patients with EBV + NK/T cell lymphoma treated at Children's Hospital of Nanjing Medical University between July 2017 and January 2022. These patients received at least two cycles of the mSMILE chemotherapy, in which a single dose of pegaspargase was substituted for 7 doses of L-asparaginase per cycle. Results: Eight patients were included in the study: one with extranodal NK/T-cell lymphoma, one with primary nodal NK/T-cell lymphoma, and six with Systemic EBV+ NK/T cell lymphoma of childhood. The results showed that five patients achieved complete remission, two achieved partial remission, and one showed progressive disease, resulting in a complete remission rate of 62.5% and an overall response rate of 87.5%. The 3-year overall survival (OS) and event-free survival (EFS) rates were 87.5% and 75%, respectively. The most common adverse reactions associated with chemotherapy were hematologic toxicities of stages III to IV. Nonhematologic adverse reactions mainly included impaired liver function, infections, and oral mucositis, which were resolved with aggressive anti-infective therapy. Conclusions: Based on our clinical experience, the mSMILE appears to be a safe and effective treatment option for EBV + NK/T-cell lymphoma, meriting further investigation in late-phase clinical trials.
RESUMEN
Purpose: This study aims to identify the key factors influencing health-related quality of life (HRQoL) of pediatric acute myeloid leukemia (AML) patients following their initial diagnosis and examine their impact on the five-year survival prognosis. Methods: A chart review and follow-up were conducted for children with AML who participated in a prospective cohort study between 2017 and 2020. We identified factors influencing HRQoL through Pediatric Quality of Life Inventory™ (PedsQL™ 4.0), PedsQL™ Cancer Module 3.0 (CM 3.0) and PedsQL™ Family Impact Module 2.0 (FIM 2.0), as well as assessed the impact of impaired HRQoL on the overall outcomes of patients. Results: Sixty-four subjects enrolled in the study had complete HRQoL outcome data, and 61 of them completed the 5-year follow-up. In CM 3.0, age was positively associated with parental proxy reports (p = 0.040), whereas divorced families were negatively associated with child self-reports (p = 0.045). A positive medical history correlates with FIM 2.0 (p = 0.025). Residence (p = 0.046), the occupation of caregivers (p = 0.014), disease severity (p = 0.024), and the only child (p = 0.029) exhibited statistically significant associations with the impairment of HRQoL. Impaired HRQoL scores shown by the PedsQL™4.0 parent proxy report (p = 0.013) and FIM 2.0 (p = 0.011) were associated with a reduced 5-year survival rate. Conclusions: This study demonstrated that early impairment of HRQoL in pediatric acute myeloid leukemia patients has predictive value for long-term prognosis. Once validated, these findings may provide some guidance to clinicians treating children with AML.
RESUMEN
Background: Hereditary spherocytosis (HS) is an autosomal dominant (AD) and autosomal recessive (AR) disorder that is mostly caused by mutations of the erythrocyte membrane-related gene ANK1. Methods: Clinical and genetic testing data of 17 HS children with ANK1 gene mutations were retrospectively collected. Clinical manifestations and phenotypic analysis of HS were summarized based on our experience and literature review. Results: A total of 17 mutations of the ANK1 gene were identified from 17 probands (12 sporadic cases and five familial cases), including 15 novel mutations and two previously reported ones. Among the 15 novel variants of ANK1, there were four non-sense mutations, four frameshift mutations, three splicing mutations, three missense mutations and one in-frame deletion of three amino acids. In the present study, HS patients with mutations in membrane binding domains had significantly lower hemoglobin (Hb) levels and higher total bilirubin (T-Bil) levels than those with mutations in regulatory domains. After reviewing and analyzing all available published reports of Chinese HS patients carrying ANK1 mutations in PubMed and Chinese journals, there were no significant differences in Hb, Ret and T-Bil between different mutation types or mutation regions. Conclusion: Mutations of the ANK1 can be inherited or de novo. Clinical manifestations of HS in children caused by ANK1 mutations are similar to those of other types of hemolytic anemia. Our report expands the mutation spectrum of HS, thus providing references for clinical management and genetic counseling of HS.
RESUMEN
OBJECTIVE: To identify key gene in childhood acute lymphoblastic leukemia (ALL) through weighted gene co-expression network analysis (WGCNA), and their enriched biological functions and signaling pathways. METHODS: Array data of the GSE73578 dataset, involving 46 childhood ALL samples, were acquired from the Gene Expression Omnibus (GEO) database. Hub modules associated with childhood ALL were screened out by WGCNA. Enriched biological functions and signaling pathways were then identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were selected by overlapping those between down-regulated genes in GSE73578, GSE4698 and the hub module. Guilt by association (GBA) was adopted to verify the function of the identified KIF11 gene and to predict its target genes. Regulatory effects of KIF11 on the proliferation and cell cycle progression of ALL in vitro were determined by cytological experiments. RESULTS: WGCNA showed that the yellow module was the most relevant to childhood ALL treatment, containing 698 genes that were enriched in cell division, mitotic nuclear division, DNA replication and DNA repair, cell cycle, DNA replication and the P53 signaling pathway. The KIF11 gene was screened out and predicted as a cell cycle mediator in childhood ALL. Knockdown of KIF11 in ALL cells inhibited cell proliferation and arrested cell cycle progression in G2/M phase. CONCLUSIONS: The KIF11 gene is critical in the treatment process of childhood ALL, which is a promising therapeutic target for childhood ALL.
Asunto(s)
Regulación Neoplásica de la Expresión Génica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Ciclo Celular/genética , Perfilación de la Expresión Génica , División Celular , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Redes Reguladoras de Genes , Cinesinas/genéticaRESUMEN
Background: Anoikis resistance (AR) plays an important role in the process of metastasis, which is an important factor affecting the risk stage of neuroblastoma (NB). This study aims to construct an anoikis-related prognostic model and analyze the characteristics of hub genes, important pathways and tumor microenvironment of anoikis-related subtypes of NB, so as to provide help for the clinical diagnosis, treatment and research of NB. Methods: We combined transcriptome data of GSE49710 and E-MTAB-8248, screened anoikis-related genes (Args) closely related to the prognosis of NB by univariate cox regression analysis, and divided the samples into anoikis-related subtypes by consistent cluster analysis. WGCNA was used to screen hub genes, GSVA and GSEA were used to analyze the differentially enriched pathways between anoikis-related subtypes. We analyzed the infiltration levels of immune cells between different groups by SsGSEA and CIBERSORT. Lasso and multivariate regression analyses were used to construct a prognostic model. Finally, we analyzed drug sensitivity through the GDSC database. Results: 721 cases and 283 Args were included in this study. All samples were grouped into two subtypes with different prognoses. The analyses of WGCNA, GSVA and GSEA suggested the existence of differentially expressed hub genes and important pathways in the two subtypes. We further constructed an anoikis-related prognostic model, in which 15 Args participated. This model had more advantages in evaluating the prognoses of NB than other commonly used clinical indicators. The infiltration levels of 9 immune cells were significantly different between different risk groups, and 13 Args involved in the model construction were correlated with the infiltration levels of immune cells. There was a relationship between the infiltration levels of 6 immune cells and riskscores. Finally, we screened 15 drugs with more obvious effects on NB in high-risk group. Conclusion: There are two anoikis-related subtypes with different prognoses in the population of NB. The anoikis-related prognostic model constructed in this study can accurately predict the prognoses of children with NB, and has a good guiding significance for clinical diagnosis, treatment and research of NB.
Asunto(s)
Anoicis , Neuroblastoma , Niño , Humanos , Anoicis/genética , Pronóstico , Neuroblastoma/genética , Análisis por Conglomerados , Bases de Datos Factuales , Microambiente Tumoral/genéticaRESUMEN
WHIM syndrome, an extremely rare congenital disease with combined immunodeficiency, is mainly caused by heterozygous gain-of-function mutation in the CXCR4 gene. There have been no previous case reports of WHIM syndrome with Kawasaki disease. We herein report a case of a boy who developed Kawasaki disease at the age of 1 year. After treatment, the number of neutrophils in his peripheral blood decreased continuously. His medical history revealed that he had been suffering from leukopenia, neutropenia and low immunoglobulin since birth, and his neutrophils could return to the normal level in the presence of infection or inflammation. Clinical targeted gene sequencing of 91 genes associated with granulocyte-related disease revealed that the patient had a novel heterozygous NM_003467; c.1032_1033delTG;p.(E345Vfs*12) variant in exon 2 of CXCR4 gene. Family verification analysis by Sanger sequencing showed that his father also had heterozygous variation at this site, while other family members did not. The computer prediction software indicated that the variation had a high pathogenicity. The computational structure analysis of the mutant revealed significant structural and functional changes in the CXCR4 protein. It should be noted that when unexplained persistent neutropenia with low immunoglobulin occurs after birth, especially when there is a family history of neutropenia, immunodeficiency should be investigated with genetic testing.
Asunto(s)
Síndrome Mucocutáneo Linfonodular , Neutropenia , Niño , China , Humanos , Inmunoglobulinas/genética , Masculino , Mutación , Neutropenia/genética , Enfermedades de Inmunodeficiencia Primaria , Receptores CXCR4/genética , VerrugasRESUMEN
Acute lymphoblastic leukemia (ALL) is the most common malignant hematological diseases in children. An immunosuppressive microenvironment, particularly regulatory T cell (Treg) infiltration, has been documented to be highly associated with childhood ALL. This present study, based on genetic factors, was aimed at investigating the mutations potentially involved in the immunosuppressive microenvironment in childhood ALL. After whole-exome sequencing was used on DNA extracted from the T cells of ALL bone marrow samples, we found the FOXC1 H446HG induced a increased Treg while decreased cytotoxic T lymphocyte (CTL) in bone marrow. The mutation of FOXC1 in T cell promoted the proliferation of leukemia cells in vitro and in vivo. CpG islands formed by insertion mutation led to an abnormal increase in exon methylation and were associated with the suppression of FOXC1. Decreased FOXC1 attenuated the transcription of HDAC1, thus resulting in the activation of KLF10 through increasing H3K27 acetylation in the promoter region. In conclusion, the de novo insertion mutation in FOXC1 induced suppression of FOXC1, thereby promoting a Treg/CTL shift in the ALL immune microenvironment. The FOXC1 H446HG mutation might be a potential therapeutic target for ALL in the future.
Asunto(s)
Factores de Transcripción Forkhead , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Factores de Transcripción Forkhead/genética , Humanos , Mutagénesis Insercional , Mutación/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Linfocitos T Reguladores , Microambiente Tumoral/genéticaRESUMEN
Background: Acute lymphocytic leukemia (ALL) is the most common malignant tumor in children. Increasing evidence suggests that circular RNAs (circRNAs) play critical regulatory roles in tumor biology. However, the expression patterns and roles of circRNAs in childhood acute lymphoblastic leukemia (ALL) remain largely unknown. Methods: circADD2 was selected by microarray assay and confirmed by qRT-PCR; in vitro effects of circADD2 were determined by CCK-8 and flow cytometry; while mice subcutaneous tumor model was designed for in vivo analysis. RNA immunoprecipitation and dual-luciferase assay were applied for mechanistic study. Protein levels were examined by Western blot assay. Results: circADD2 was down-regulated in ALL tissues and cell lines. Overexpression of circADD2 inhibited cell proliferation and promoted apoptosis both in vitro and in vivo. Briefly, circADD2 could directly sponge miR-149-5p, and the level of AKT2, a target gene of miR-149-5p, was downregulated by circADD2. Conclusion: circADD2, as a tumor suppressor in ALL, can sponge miR-149-5p, and may serve as a potential biomarker for the diagnosis or treatment of ALL.
RESUMEN
BACKGROUND: In the past decade, miR-100, miR-146a, and miR-210 were reported to be dysregulated in childhood acute lymphoblastic leukemia (ALL). However, effects of genetic variants in these three microRNAs have not been investigated in Chinese population. METHODS: In this study, we conducted a case-control study to evaluate the relationship between genetic variants in miR-100, miR-146a, and miR-210 and the risk of childhood ALL in Chinese population. Subsequently, plasma expression level of miR-100 was also detected. RESULT: We found that subjects carrying mutant homozygous TT genotype of miR-100 rs543412 had a statistically significantly decreased risk of childhood ALL (adjusted odds ratio [OR] = 0.73, 95% confidence interval [CI] = 0.55-0.97, P = 0.029). This protective effect was also observed among subjects whose parents were ever drinkers (adjusted OR = 0.53, 95% CI = 0.29-0.94), or whose living house were ever painted (adjusted OR = 0.57, 95% CI = 0.34-0.94). Besides, rs543412 variant homozygous TT had a significantly protective role in patients with childhood B-ALL. Finally, we found that expression level of miR-100 in plasma of childhood ALL cases was significantly higher than that of noncancer controls. CONCLUSION: Our study suggested that there was significant association between the polymorphisms in miR-100 (rs543412) and decreased susceptibility to childhood ALL.
Asunto(s)
MicroARNs/genética , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Regulación hacia Arriba , Adolescente , Pueblo Asiatico/genética , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Regulación Neoplásica de la Expresión Génica , Estudios de Asociación Genética , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Factores ProtectoresRESUMEN
OBJECTIVE: Fusion gene detection is widely used in the diagnosis and treatment of leukemia. This study developed a rapid detection method of eight common pediatric leukemia fusion genes. METHODS: In this study, one step multiplex RT-PCR assay was developed for the simultaneous detection of eight common leukemia fusion genes, including BCR-ABL, ETV6-RUNX1, MLL-AF4, E2A-PBX1, AML1-ETO, PML-RARα, CBFß-MYH11 and SIL-TAL1. The single step RT-PCR approach is mediated by universal primers after obtaining total RNA from bone marrow specimens. The size of the amplified fragments were analyzed by capillary electrophoresis assay. A total of 122 patients with positive leukemia fusion genes were tested by real-time PCR. RESULTS: Respectively, 21 cases were detected as CBRB-MYH11 fusion gene, 13 cases were detected as SIL-TAL1 fusion gene, 16 cases were detected as ETV6-RUNX1 fusion gene, 16 cases were detected as E2A-PBX1 fusion gene, 15 cases were detected as PML-RARα fusion gene, 14 cases were detected as AML1-ETO fusion gene, 13 cases were detected as MLL-AF4 fusion gene, except for 1 case where no fusion gene was detected. CONCLUSION: This method has a high accuracy and detection rate. Therefore, one step multiplex RT-PCR combined with a capillary electrophoresis analysis system can be used as an important tool for the clinical diagnosis, treatment and prognosis of pediatric leukemia.
RESUMEN
Immune escape due to immunosuppressive microenvironments, such as those associated with regulatory T (Treg) cells is highly associated with initial occurrence and development of solid tumors or hematologic malignancies. Here, we employed high-throughput transcriptome screening to demonstrate immunosuppression-associated increases in the long noncoding (lnc) RNA lnc-insulin receptor precursor (INSR), which was corrected with INSR expression in CD4+ T cells extracted from the bone marrow of patients with childhood acute T lymphoblastic leukemia. Loss-of-function and gain-of-function assays in vitro and in vivo revealed that membrane-localized and cytoplasm-localized lnc-INSR promoted Treg distribution and decreased the percentage of cytotoxic T lymphocytes, which induced tumor growth. Through direct binding with INSR, lnc-INSR blocked the INSR ubiquitination site, causing abnormal activation of INSR and the phosphatidylinositide 3-kinase/AKT-signaling pathway. These results indicated that lnc-INSR might promote immune suppression by enhancing Treg-cell differentiation and serve as valuable therapeutic targets in the immunosuppressive tumor microenvironment.
Asunto(s)
Antígenos CD/inmunología , Médula Ósea/inmunología , Leucemia-Linfoma Linfoblástico de Células Precursoras/inmunología , ARN Largo no Codificante/inmunología , Receptor de Insulina/inmunología , Microambiente Tumoral/genética , Adolescente , Animales , Linfocitos T CD4-Positivos/inmunología , Línea Celular Tumoral , Proliferación Celular/fisiología , Niño , Humanos , Terapia de Inmunosupresión/métodos , Células Jurkat , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Fosfatidilinositol 3-Quinasa/inmunología , Proteínas Proto-Oncogénicas c-akt/inmunología , Transducción de Señal/inmunología , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/inmunología , Transcriptoma/inmunologíaRESUMEN
BACKGROUND & AIMS: Age at diagnosis is a key factor for predicting the prognosis of pediatric leukemia especially regarding the survivorship assessment. In this study, we aimed to assess the impact of this prognostic factor such as age in children with pediatric leukemia. METHODS: In this study, Surveillance, Epidemiology, and End Results Program-registered children with leukemia during 1988-2013 were analyzed. All patients were divided into five groups according to the age at the time of diagnosis (<1, 1-4, 5-9, 10-15, >15 years old). Kaplan-Meier and multivariable Cox regression models were used to evaluate leukemia survival outcomes and risk factors. RESULTS: There was significant variability in pediatric leukemia survival by age at diagnosis including ALL, AML and CML subtypes. According to the survival curves in each group, survival rate were peaked among children diagnosed at 1-4 years and steadily declined among those diagnosed at older ages in children with ALL. Infants (<1 year) had the lowest survivorship in children with either ALL or AML. However, children (1-4 years) harbored the worst prognosis suffering from CML. A stratified analysis of the effect of age at diagnosis was validated as independent predictors for the prognosis of pediatric leukemia. CONCLUSIONS: Age at diagnosis remained to be a crucial determinant of the survival variability of pediatric leukemia patients.
Asunto(s)
Leucemia/epidemiología , Adolescente , Distribución por Edad , Factores de Edad , Distribución de Chi-Cuadrado , Niño , Preescolar , Bases de Datos Factuales , Femenino , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Leucemia/diagnóstico , Leucemia/mortalidad , Leucemia/terapia , Masculino , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Programa de VERF , Factores de Tiempo , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: In the past decades, a good deal of studies has provided the possibility of the circulating microRNAs (miRNAs) as noninvasive biomarkers for cancer diagnosis. The aim of our study was to detect the levels of circulating miRNAs in tissues and plasmas of gastric cancer (GC) patients and evaluate their diagnostic value. METHODS: Tissue samples were collected from 85 GC patients. Plasma samples were collected from 285 GC patients and 285 matched controls. Differentially expressed miRNAs were filtered with by Agilent Human miRNA Microarray and TaqMan low density array (TLDA) with pooled samples, followed by the quantitative reverse transcription polymerase chain reaction (qRT-PCR) validation. Receiver operating characteristic (ROC) curves were structured to evaluate the diagnostic accuracy of the miRNAs. The plasma level of miR-26a in GC patients of different clinical stages was compared. RESULTS: Four miRNAs (miR-26a, miR-142-3p, miR-148a, and miR-195) revealed coincidentally decreased levels in tissue and plasma of the GC patients compared with controls, and ROC curves were constructed to demonstrate that miR-26a had a highest area under the ROC curve (AUC) of 0.882. Furthermore, miR-26a was stably detected in the plasma of GC patients with different clinical characteristics. CONCLUSION: Plasma miR-26a may provide a novel and stable marker of gastric cancer.
Asunto(s)
MicroARNs/sangre , Neoplasias Gástricas/sangre , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Femenino , Humanos , Masculino , MicroARNs/análisis , MicroARNs/genética , Persona de Mediana Edad , Curva ROC , Estómago/patología , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , TranscriptomaRESUMEN
Single nucleotide polymorphisms (SNPs) in the 3'-untranslated regions targeted by putative mircoRNA can change its binding strength, affecting the susceptibility and prognosis of cancer. We aimed to investigate the associations between SNPs within miR-148a binding sites and gastric cancer (GC) risk and prognosis. Using bioinformatics tools, we selected two SNPs (SCRN1 rs6976789 and PDYN rs2235749) located in miR-148a target sites. We genotyped the two SNPs in a case-control study comprising 753 GC patients and 949 cancer-free subjects. We found a significantly increased risk of GC associated with the SCRN1 rs6976789 C>T polymorphism [adjusted OR = 1.25, 95% confidence interval (CI) = 1.02-1.53; CT/TT vs. CC]. However, no significant association was found between the PDYN rs2235749 and GC risk in all genetic models. Furthermore, we evaluated whether SCRN1 rs6976789 affected the survival of GC patients. Results showed that individuals with SCRN1 rs6976789 TT genotype had poorer overall survival compared with those carried CC/CT genotypes in intestinal-type GC (adjusted HR = 2.47, 95% CI = 1.21-5.05). Luciferase report assay showed that the rs6976789 variant T allele influenced the binding ability of miR-148a. Our results suggested that the SCRN1 rs6976789 polymorphism may play an important role in the GC development and progression.
Asunto(s)
Estudios de Asociación Genética , MicroARNs/genética , Proteínas del Tejido Nervioso/genética , Neoplasias Gástricas/genética , Regiones no Traducidas 3' , Anciano , Anciano de 80 o más Años , Sitios de Unión/genética , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , MicroARNs/metabolismo , Polimorfismo de Nucleótido Simple , Pronóstico , Neoplasias Gástricas/patologíaRESUMEN
A recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate the association between the SNP rs10484761 and gastric cancer survival. In the dominant model, those who carry TC/CC genotypes had a significant shorter survival time (log-rank P=0.005), especially in the subgroups of aged male patients, cardia intestinal tumor (HR=1.41, 95% CI=1.08-1.84 for cardia cancer and HR=1.64, 95% CI=1.14-2.37 for intestinal-type), tumor size ≤ 5 cm (HR=1.41, 95% CI=0.56-0.99), T1 depth invasion (HR=2.34, 95% CI=1.20-4.56), lymph node metastasis (HR=1.51, 95% CI=1.19-1.96), no distant metastasis (HR=1.33, 95% CI=1.05-1.68), TNM stage III+IV (HR=1.50, 95% CI=1.13-1.98), and with chemotherapy (HR=1.53, 95% CI=1.17-1.99). The results indicated that SNP rs10484761 was associated with prognosis of gastric cancer, suggesting that this genetic variant may serve as a potential marker to predict the survival of gastric cancer in Chinese population.