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Multiple myeloma (MM) is an incurable hematological malignancy with poor survival. Accumulating evidence reveals that lactylation modification plays a vital role in tumorigenesis. However, research on lactylation-related genes (LRGs) in predicting the prognosis of MM remains limited. Differentially expressed LRGs (DELRGs) between MM and normal samples were investigated from the Gene Expression Omnibus database. Univariate Cox regression and LASSO Cox regression analysis were applied to construct gene signature associated with overall survival. The signature was validated in two external datasets. A nomogram was further constructed and evaluated. Additionally, Enrichment analysis, immune analysis, and drug chemosensitivity analysis between the two groups were investigated. qPCR and immunofluorescence staining were performed to validate the expression and localization of PFN1. CCK-8 and flow cytometry were performed to validate biological function. A total of 9 LRGs (TRIM28, PPIA, SOD1, RRP1B, IARS2, RB1, PFN1, PRCC, and FABP5) were selected to establish the prognostic signature. Kaplan-Meier survival curves showed that high-risk group patients had a remarkably worse prognosis in the training and validation cohorts. A nomogram was constructed based on LRGs signature and clinical characteristics, and showed excellent predictive power by calibration curve and C-index. Moreover, biological pathways, immunologic status, as well as sensitivity to chemotherapy drugs were different between high- and low-risk groups. Additionally, the hub gene PFN1 is highly expressed in MM, knocking down PFN1 induces cell cycle arrest, suppresses cell proliferation and promotes cell apoptosis. In conclusion, our study revealed that LRGs signature is a promising biomarker for MM that can effectively early distinguish high-risk patients and predict prognosis.
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Biomarcadores de Tumor , Regulación Neoplásica de la Expresión Génica , Mieloma Múltiple , Profilinas , Humanos , Mieloma Múltiple/genética , Mieloma Múltiple/mortalidad , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/patología , Pronóstico , Profilinas/genética , Profilinas/metabolismo , Biomarcadores de Tumor/genética , Masculino , Femenino , Nomogramas , Proliferación Celular/genética , Perfilación de la Expresión Génica , Estimación de Kaplan-Meier , Línea Celular Tumoral , Transcriptoma , Apoptosis/genética , Persona de Mediana EdadRESUMEN
BACKGROUND: CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due to their overlapping clinical features. Promptly distinguishing between CRS and infection post CD19 target CAR-T cell infusion (CTI) remains a clinical dilemma. Our study aimed to analyze the incidence of infections and identify key indicators for early infection detection in febrile patients within 30 days post-CTI for B-cell malignancies. METHODS: In this retrospective cohort study, a cohort of 104 consecutive patients with R/R B-cell malignancies who underwent CAR-T therapy was reviewed. Clinical data including age, gender, CRS, ICANS, treatment history, infection incidence, and treatment responses were collected. Serum biomarkers procalcitonin (PCT), interleukin-6 (IL-6), and C-reactive protein (CRP) levels were analyzed using chemiluminescent assays. Statistical analyses employed Pearson's Chi-square test, t-test, Mann-Whitney U-test, Kaplan-Meier survival analysis, Cox proportional hazards regression model, Spearman rank correlation, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic accuracy and develop predictive models through multivariate logistic regression. RESULTS: In this study, 38 patients (36.5%) experienced infections (30 bacterial, 5 fungal, and 3 viral) within the first 30 days of CAR T-cell infusion. In general, bacterial, fungal, and viral infections were detected at a median of 7, 8, and 9 days, respectively, after CAR T-cell infusion. Prior allogeneic hematopoietic cell transplantation (HCT) was an independent risk factor for infection (Hazard Ratio [HR]: 4.432 [1.262-15.565], P = 0.020). Furthermore, CRS was an independent risk factor for both infection ((HR: 2.903 [1.577-5.345], P < 0.001) and severe infection (9.040 [2.256-36.232], P < 0.001). Serum PCT, IL-6, and CRP were valuable in early infection prediction post-CAR-T therapy, particularly PCT with the highest area under the ROC curve (AUC) of 0.897. A diagnostic model incorporating PCT and CRP demonstrated an AUC of 0.903 with sensitivity and specificity above 83%. For severe infections, a model including CRS severity and PCT showed an exceptional AUC of 0.991 with perfect sensitivity and high specificity. Based on the aforementioned analysis, we proposed a workflow for the rapid identification of early infection during CAR-T cell therapy. CONCLUSIONS: CRS and prior allogeneic HCT are independent infection risk factors post-CTI in febrile B-cell malignancy patients. Our identification of novel models using PCT and CRP for predicting infection, and PCT and CRS for predicting severe infection, offers potential to guide therapeutic decisions and enhance the efficacy of CAR-T cell therapy in the future.
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Antígenos CD19 , Fiebre , Inmunoterapia Adoptiva , Humanos , Femenino , Masculino , Persona de Mediana Edad , Inmunoterapia Adoptiva/métodos , Adulto , Antígenos CD19/metabolismo , Infecciones/sangre , Anciano , Curva ROC , Adulto Joven , Estudios RetrospectivosRESUMEN
Differentiation therapy based on ATRA almost cured acute promyelocytic leukemia (APL). However, it is disappointing that ATRA is not effective against other acute myeloid leukemia (AML) subtypes. Developing new and effective anti-AML therapies that promote leukemia differentiation is necessary. The CDK4/6-cyclin D pathway is a key initiator of the G1-S phase transition, which determines cell fate. Herein, we investigated whether the CDK4/6 inhibitor palbociclib would synergize with ATRA to promote leukemia differentiation in vitro and in vivo. Our findings revealed that CDK4/6-cyclin D pathway genes were aberrantly expressed in AML, and we observed that palbociclib sensitized AML cells to ATRA-induced morphologic, biochemical, and functional changes indicative of myeloid differentiation. The combination of palbociclib and ATRA attenuated AML cell expansion in vivo. These enhanced differentiation effects may be associated with the regulation of transcription factors, including RARα, E2F1, and STAT1. Overall, our findings demonstrate that CDK4/6 inhibition sensitizes AML cells to ATRA and could guide the development of novel therapeutic strategies for patients with AML.
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Diferenciación Celular , Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Sinergismo Farmacológico , Leucemia Mieloide Aguda , Piperazinas , Piridinas , Tretinoina , Humanos , Piperazinas/farmacología , Piridinas/farmacología , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/genética , Diferenciación Celular/efectos de los fármacos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Animales , Ratones , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Tretinoina/farmacología , Línea Celular Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto , Proliferación Celular/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacologíaRESUMEN
Myeloid-derived suppressor cells (MDSCs) are implicated in the regulation of immune responses closely associated with poor clinical outcomes in cancer. However, the MDSC subtypes in non-Hodgkin's lymphoma (NHL) have not been systematically investigated. So, we investigated the percentage of MDSC subsets in 78 newly diagnosed NHL patients by flow cytometry. The results showed that all MDSC subsets increased in NHL patients compared with healthy donors. Notably, MDSCs, monocytic MDSCs, and CD14 + CD66b + MDSCs significantly increased in NHL patients compared with those with lymphadenitis donors. polymorphonuclear MDSCs (PMN-MDSCs), early-stage MDSCs (e-MDSCs), and the International Prognostic Index were independent risk factors for poor clinical efficacy and were involved in constructing the nomogram for predicting clinical efficacy. Progression-free survival (PFS) was significantly shorter in patients with high level of MDSC subsets, and PMN-MDSCs emerged as an independent prognostic factor for PFS. PMN-MDSCs, e-MDSCs, and the International Prognostic Index were involved in constructing the nomogram for predicting PFS. Patients with a higher percentage of MDSCs, PMN-MDSCs, e-MDSCs, and CD14 + CD66b + MDSCs experienced a shorter overall survival compared with those with lower percentages. In addition, research on mechanisms found that T cell function was suppressed and mediated by the expansion of MDSCs via involving arginase-1 and interleukin-10 in vitro and in vivo. In conclusion, our study demonstrates that the increased circulating MDSC subsets predict poor clinical efficacy and prognosis in NHL, potentially involving T cell suppression through MDSC subset expansion. These findings indicate the potential of MDSC subsets as comprehensive diagnostic, prognostic biomarkers, and therapeutic targets for NHL.
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Linfoma no Hodgkin , Células Supresoras de Origen Mieloide , Humanos , Células Supresoras de Origen Mieloide/inmunología , Masculino , Femenino , Persona de Mediana Edad , Linfoma no Hodgkin/inmunología , Linfoma no Hodgkin/patología , Linfoma no Hodgkin/mortalidad , Linfoma no Hodgkin/diagnóstico , Pronóstico , Adulto , Linfocitos T/inmunología , Anciano , Animales , Ratones , Arginasa/metabolismoRESUMEN
Wilms tumor gene 1 (WT-1 gene) is overexpressed in most patients with acute myeloid leukemia (AML) and is an indicator for minimal residual disease (MRD) monitoring, but because the WT-1 gene has relatively low specificity, further studies of the prognostic value of a combination of the WT-1 and other genes are needed. The aim of this study was to explore the prognostic value of the WT-1 gene combined with recurrent cytogenetic genes in AML. In AML, the transcript expression of the WT-1 gene was closely related to leukemic tumor burden and acted as an accurate molecular indicator for MRD detection. Most patients with low expression levels of the WT-1 gene after induction and consolidation therapy were significantly associated with favorable relapse-free survival (RFS) and overall survival (OS), but 17.6% of patients relapsed and died of primary disease. However, when analyzing the WT-1 gene combined with recurrent cytogenetic genes, none of the patients with low expression levels of the WT-1 gene and recurrent cytogenetic genes negative relapsed and died in the median follow-up time of 19 months (range: 3-94 months). Thus, the combination of the WT-1 gene and recurrent cytogenetic genes is a more accurate indicator for MRD monitoring and prognosis evaluation in AML patients.
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Genes del Tumor de Wilms , Leucemia Mieloide Aguda , Humanos , Pronóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Recurrencia , Neoplasia Residual/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/patología , Análisis CitogenéticoRESUMEN
Previous studies on the prognostic value of soluble programmed cell death ligand 1 (sPD-L1) in lymphoma patients have yielded inconsistent results. Here, we conducted a meta-analysis and systematic review to investigate the prognostic significance of sPD-L1 in lymphoma, especially in diffuse large B-cell lymphoma (DLBCL) and NK/T-cell lymphoma (NK/TCL). A total of 11 studies with 1185 patients were included in the meta-analysis, and the combined results indicated that high sPD-L1 levels were associated with worse overall survival (OS) (HR = 2.27, 95%CI: 1.70-3.04) and progression-free survival (PFS) (HR = 2.68, 95%CI: 1.92-3.75). Furthermore, subgroup analysis showed that sPD-L1 remained a significant prognostic factor for OS. The meta-analysis indicated that sPD-L1 may be a potential prognostic biomarker for lymphoma, especially in DLBCL and NK/TCL, and high sPD-L1 levels were associated with worse survival prognosis.
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Linfoma de Células B Grandes Difuso , Linfoma de Células T Periférico , Humanos , Pronóstico , Ligandos , Linfoma de Células B Grandes Difuso/patología , Apoptosis , Antígeno B7-H1 , Biomarcadores de TumorRESUMEN
The objective of this study was to investigate the expression pattern of Wilms tumor 1 (WT1) gene at diagnosis, complete remission (CR) and relapse status in non-acute promyelocytic leukemia (non-APL) acute myeloid leukemia (AML) patients, and further explore the prognostic value of measurable residual disease (MRD) assessment by WT1 gene and multiparameter flow cytometry (MFC). Our results showed that the average expression level of WT1 was 4026 ± 616.1 copies/104 ABL at diagnosis, 155.3 ± 36.03 copies/104 ABL at CR, and 1766 ± 238.8 copies/104 ABL at relapse, with statistically significant differences (p = .000). ROC analysis showed that WT1 expression levels were 118.1 copies/104 ABL and MFC-MRD was 0.155%, which had good predictive efficacy for relapse of patients during consolidation therapy. Both WT1-MRD and MFC-MRD had a significant impact on relapse-free survival (RFS) and overall survival (OS). Patients with WT1-MRD positive or MFC-MRD positive were associated with worse RFS (HR 3.840, 95% CI 1.582-9.320, p = .003), (HR 4.464, 95% CI 1.841-10.984, p = .001) and worse OS (HR 2.963, 95% CI 1.058-8.295, p = .039), (HR 3.590, 95% CI 1.254-10.280, p = .017). Besides, compared with patients who were negative for both WT1-MRD and MFC-MRD, patients who were positive both WT1-MRD and MFC-MRD were associated with worse RFS (HR 6.200, 95% CI 2.206-17.430, p = .001) and worse OS (HR 4.886, 95% CI 1.388-17.197, p = .013). This study demonstrates that combined assessment of MRD by WT1 and MFC improves relapse and prognosis prediction in non-APL AML patients, and may help guide interventions for disease relapse.
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Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Humanos , Pronóstico , Citometría de Flujo/métodos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Inducción de Remisión , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Proteínas WT1/genética , Proteínas WT1/metabolismoRESUMEN
BACKGROUND: Multiple myeloma is an incurable hematologic malignancy, its early diagnosis is important. However, the biomarker for early diagnosis is limited; hence more need to be identified. The present study aimed to explore the easily tested new biomarker in multiple myeloma by weighted gene co-expression network analysis (WGCNA). METHODS: Differentially expressed genes (DEGs) were screened using GSE47552. WGCNA was used to screen hub genes. Subsequently. Hub genes of multiple myeloma were obtained by intersection of DEGs and WGCNA. We used the T-test to screen highly expressed genes. Then, the diagnostic value of key genes was evaluated by the receiver operating characteristic (ROC) curve. Finally, expression levels of key genes were tested and proved by RT-PCR. RESULTS: 278 DEGs were screened by Limma package. Three modules were most significantly correlated with multiple myeloma. 238 key genes were screened after the intersection of WGCNA with DEGs. In addition, SNORNA is rarely studied in multiple myeloma, and ROC curve analysis in our prediction model showed that SNORA71A had a good prediction effect (p = 0.07). The expression of SNORA71A was increased in samples of multiple myeloma (P = 0.05). RT-PCR results showed that SNORA71A was upregulated in 51 patient specimens compared to the healthy group (P < 0.05). Linear correlation analysis showed that creatinine was positively correlated with SNORA71A (r = 0.49 P = 0.0002). CONCLUSIONS: This study found that SNORA71A was up-regulated and associated with the clinical stages in multiple myeloma; it suggests that SNORA71A could be used as a novel biomarker for early diagnosis and a potential therapeutic target in multiple myeloma.
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Biomarcadores de Tumor/metabolismo , Redes Reguladoras de Genes/genética , Mieloma Múltiple/genética , Transcriptoma/genética , Diagnóstico Precoz , HumanosRESUMEN
Tumor endothelial marker 8 (TEM8), also known as ANTXR1, was highly expressed in cancers, and was identified as a biomarker for early diagnosis and prognosis in some cancers. However, the clinical role and molecular mechanisms of TEM8 in lung adenocarcinoma (LUAD) are still unclear. The present study aimed to explore its clinical value and the molecular mechanisms of TEM8 underlying the progression of LUAD. Our study found the elevation of TEM8 in LUAD cell lines and tissues. What's more, we observed that the TEM8 expression level was associated with tumor size, primary tumor, and AJCC stage, and LUAD patients with high TEM8 expression usually have a poor prognosis. Then, we conducted a series of experiments by the strategy of loss-of-function and gain-of-function, and our results suggested that the knockdown of TEM8 suppressed proliferation, migration, and invasion and induced apoptosis in LUAD whereas overexpression of TEM8 had the opposite effect. Molecular mechanistic investigation showed that TEM8 exerted its promoting effects mainly through activating the Wnt/ß-catenin signaling pathway. In short, our findings suggested that TEM8 played a crucial role in the progression of LUAD by activating the Wnt/ß-catenin signaling pathway and could serve as a potential therapeutic target for LUAD.
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BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous malignancy with varied outcomes. However, the fundamental mechanisms remain to be fully defined. AIM: We aimed to identify core differentially co-expressed hub genes and perturbed pathways relevant to the pathogenesis and prognosis of DLBCL. METHODS: We retrieved the raw gene expression profile and clinical information of GSE12453 from the Gene Expression Omnibus (GEO) database. We used integrated bioinformatics analysis to identify differentially co-expressed genes. The CIBERSORT analysis was also applied to predict tumor-infiltrating immune cells (TIICs) in the GSE12453 dataset. We performed survival and ssGSEA (single-sample Gene Set Enrichment Analysis) (for TIICs) analyses and validated the hub genes using GEPIA2 and an independent GSE31312 dataset. RESULTS: We identified 46 differentially co-expressed hub genes in the GSE12453 dataset. Gene expression levels and survival analysis found 15 differentially co-expressed core hub genes. The core genes prognostic values and expression levels were further validated in the GEPIA2 database and GSE31312 dataset to be reliable (p < 0.01). The core genes' main KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichments were Ribosome and Coronavirus disease-COVID-19. High expressions of the 15 core hub genes had prognostic value in DLBCL. The core genes showed significant predictive accuracy in distinguishing DLBCL cases from non-tumor controls, with the area under the curve (AUC) ranging from 0.992 to 1.00. Finally, CIBERSORT analysis on GSE12453 revealed immune cells, including activated memory CD4+ T cells and M0, M1, and M2-macrophages as the infiltrates in the DLBCL microenvironment. CONCLUSION: Our study found differentially co-expressed core hub genes and relevant pathways involved in ribosome and COVID-19 disease that may be potential targets for prognosis and novel therapeutic intervention in DLBCL.
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BACKGROUND: Multiple myeloma (MM), the second most hematological malignancy, has high incidence and remains incurable till now. The pathogenesis of MM is poorly understood. This study aimed to identify novel prognostic model for MM on gene expression profiles. METHODS: Gene expression datas of MM (GSE6477, GSE136337) were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in GSE6477 between case samples and normal control samples were screened by the limma package. Meanwhile, enrichment analysis was conducted, and a protein-protein interaction (PPI) network of these DEGs was established by STRING and cytoscape software. Co-expression modules of genes were built by Weighted Correlation Network Analysis (WGCNA). Key genes were identified both from hub genes and the DEGs. Univariate and multivariate Cox congression were performed to screen independent prognostic genes to construct a predictive model. The predictive power of the model was evaluated by Kaplan-Meier curve and time-dependent receiver operating characteristic (ROC) curves. Finally, univariate and multivariate Cox regression analyse were used to investigate whether the prognostic model could be independent of other clinical parameters. RESULTS: GSE6477, including 101 case and 15 normal control, were screened as the datasets. A total of 178 DEGs were identified, including 59 up-regulated and 119 down-regulated genes. In WGCNA analysis, module black and module purple were the most relevant modules with cancer traits, and 92 hub genes in these two modules were selected for further analysis. Next, 47 genes were chosen both from the DEGs and hub genes as key genes. Three genes (LYVE1, RNASE1, and RNASE2) were finally screened by univariate and multivariate Cox regression analyses and used to construct a risk model. In addition, the three-gene prognostic model revealed independent and accurate prognostic capacity in relation to other clinical parameters for MM patients. CONCLUSION: In summary, we identified and constructed a three-gene-based prognostic model that could be used to predict overall survival of MM patients.
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Chimeric antigen receptor (CAR) T cell therapy improves the remission rate of refractory/relapsed B-acute lymphoblastic leukemia (R/R B-ALL) patients, but the relapse rate remains high. Recent studies suggest patients who underwent post-chimeric antigen receptor T cell therapy hematopoietic stem cell transplantation (post- HSCT) would achieve durable remission and better survival, but this remains controversial. To this end, we conducted a meta-analysis to assess the role of post-HSCT in R/R B-ALL. The Cochrane Library, Embase, and PubMed were used to identify relevant studies; the latest search update was on July 05, 2020. We used the Cochran Q test and I-squared statistics to test for heterogeneity among the studies analyzed. The fixed model and random model were used to combine results when appropriate. We performed all statistical analyses with Stata 12, and P < 0.05 was considered statistically significant. We included 18 studies with 758 patients in the meta-analysis. Our results indicated that post-HSCT was associated with lower relapse rate (RR: 0.40, 95% CI: 0.32-0.50, P = 0.000), better overall survival (HR: 0.37, 95% CI: 0.19-0.71, P = 0.003), better leukemia-free survival (HR: 0.20, 95% CI: 0.10-0.40, P = 0.000). However, post-HSCT did not influence OS in Caucasians, and CAR-T cells with CD28 co-stimulation factor bridged to HSCT did not influence OS. Post-HSCT decreased the relapse rate and improved the long-term survival of R/R B-ALL patients. R/R B-ALL patients would benefit from post-HSCT after CAR-T cell therapy.
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Trasplante de Células Madre Hematopoyéticas , Inmunoterapia Adoptiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Terapia Recuperativa , Antígenos CD19/inmunología , Pueblo Asiatico , Supervivencia sin Enfermedad , Estudios Epidemiológicos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnología , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Pronóstico , Recurrencia , Inducción de Remisión , Resultado del Tratamiento , Población BlancaRESUMEN
Long non-coding RNA HOTAIR has been reported to play a key role in regulating various biological processes in various cancers. However, the roles and mechanisms of HOTAIR in acute myeloid leukaemia (AML) are still unclear and need to be investigated. In this study, we induced differentiation of four AML cell lines by all-trans retinoic acid (ATRA) and found HOTAIR was significantly upregulated in the process. Chromatin immunoprecipitation (ChIP) assays indicated that C/EBPß upregulated HOTAIR during ATRA induced differentiation in HL-60 cells. By gain- and loss-of-function analysis, we then observed that HOTAIR expression was positively correlated with ATRA-induced differentiation and negatively regulated G1 phase arrest in HL-60 cells. In addition, we found that HOTAIR promoted ATRA-induced differentiation via the regulation of the cell cycle regulator p21 via miR-17-5p. Moreover, we detected the expression of HOTAIR in 84 de novo AML patients, HOTAIR was found significantly downregulated in the AML patients compared to the iron deficiency anaemia (IDA) control group, negatively correlated with the platelet level in M2 patients. In all, our data suggest that HOTAIR may be subtype-specific in AML-M2 patients, also HOTAIR regulates AML differentiation by C/EBPBß/HOTAIR/miR-17-5p/p21 pathway. The findings of the present study provide a novel insight into the mechanism of lncRNA-mediated differentiation and indicate that HOTAIR may be a promising therapeutic target for leukaemia, especially for AML with M2 type.Abbreviation: AML: acute myeloid leukaemia; APL: acute promyelocytic leukaemia; ATRA: all-trans retinoic acid; CCK8: cell Counting Kit-8; CDKs: cyclin-dependent kinases ; CeRNA: competing endogenous RNAs; ChIP: chromatin immunoprecipitation; CHX: cycloheximide; FAB: French-American-British; FCM: flow cytometry; HOTAIR: HOX transcript antisense RNA; IDA: iron-deficiency anemia; lncRNA: long non-coding RNA; 3'UTR: 3'untranslated region; MT: Mutation type; WT: Wild type; qRT-PCR: Quantitative real-time PCR.
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Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Regulación hacia Abajo , Leucemia Mieloide Aguda/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Estudios de Casos y Controles , Ciclo Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Niño , Preescolar , Regulación hacia Abajo/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HL-60 , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Tretinoina/farmacología , Adulto JovenRESUMEN
A flow cytometric score (FCM-score) to diagnose myelodysplastic syndromes (MDS) was proposed in 2012 that used four parameters to distinguish low-grade MDS from non-clonal cytopenias. This study was carried out to further simplify the method for better clinical application. Combinations of antibodies CD34, CD19, CD33 and CD45 were analyzed for the four parameters. Compared with the published method that used low side scatter (SSC) and CD45 expression to separate B lymphocyte progenitor cells and myeloblasts, our method (MFCM-Score) used CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34+CD45dimm population. Subjects were analyzed and compared using the two schemes. In addition, the relationships between the MFCM-Score and the Revised International Prognostic Scoring System (IPSS-R) for MDS were analyzed. There was no significant difference between the MFCM-score and FCM-score in the diagnosis of MDS (P > 0.05); MFCM-score had a positive correlation with the IPSS-R prognosis classification for MDS (Spearman r = 0.848, P < 0.001). All parameters in the MFCM-score were positively correlated to the IPSS-R grades in MDS (P < 0.01). Our work demonstrates that the FCM score using four parameters is simple and practical for screening MDS patients and the MFCM-score could be used to evaluate the risk of MDS patients.
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BACKGROUND: Elevated red blood cell distribution width (RDW) and decreased platelet count (PLT) can be clinically relevant to the prognosis in cancer patients. However, their prognostic values in patients with diffuse large B-cell lymphoma (DLBCL) need to be further explored. METHODS: Healthy donors (n = 130) and patients with DLBCL (n = 349) were included and evaluated retrospectively in this study. The prognostic influence of clinical and pathological factors including RDW and PLT on overall survival (OS) and progression-free survival (PFS) were studied by Kaplan-Meier curves. To evaluate the independent prognostic relevance of RDW and PLT, univariate and multivariate Cox proportional hazards regression models were applied. The adjusted IPI model was established based on the results of multivariate analysis, and verified by Harrell's C statistical analysis. RESULTS: Kaplan-Meier curves indicated that an elevated RDW value and thrombocytopenia are poor factors for OS (P < 0.001, P = 0.006) and PFS (P = 0.003, P < 0.001) in DLBCL patients. Multivariate analysis confirmed that elevated RDW value (HR = 2.026, 95%CI = 1.263-3.250, P = 0.003) and decreased PLT count (HR =1.749, 95%CI = 1.010-3.028, P = 0.046) were both independent prognostic factors. The c-index of IPI and NCCN-IPI were increased when RDW level and PLT were supplemented in our cohort. CONCLUSIONS: Our study shows that elevated RDW level and decreased PLT are independent poor prognostic factors in newly diagnosed DLBCL patients. Adding RDW and PLT to the IPI score may improve its predictive ability, and the adjusted IPI may be more powerful in predicting the survival of DLBCL patients in the rituximab era.
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Biomarcadores de Tumor/sangre , Plaquetas/patología , Eritrocitos/patología , Linfoma de Células B Grandes Difuso/sangre , Nomogramas , Estudios de Casos y Controles , Índices de Eritrocitos , Femenino , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Pronóstico , Estudios RetrospectivosRESUMEN
Myeloid-derived suppressor cells (MDSCs) comprise of a population of cells, which suppress the innate and adaptive immune system via different mechanisms. MDSCs are accumulated under pathological conditions. The present study aimed to clarify the pathological role of MDSCs in systemic lupus erythematosus (SLE) patients. Consequently, the level of circulating M-MDSCs was significantly increased in newly diagnosed SLE patients as compared to healthy controls. An elevated level of M-MDSCs was positively correlated with the disease severity in SLE patients and an immunosuppressive role was exerted in an iNOS-dependent manner. The decrease in the number of M-MDSCs after therapy rendered them as an indicator for the efficacy of treatment. These results demonstrated that M-MDSCs participated in the pathological progress in SLE patients. Thus, MDSCs are attractive biomarkers and therapeutic targets for SLE patients.
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Lupus Eritematoso Sistémico/inmunología , Células Supresoras de Origen Mieloide/inmunología , Óxido Nítrico Sintasa de Tipo II/fisiología , Adolescente , Adulto , Linfocitos T CD4-Positivos/inmunología , Antígenos HLA-DR/análisis , Humanos , Tolerancia Inmunológica , Interferón gamma/biosíntesis , Interferón gamma/genética , Leucocitos Mononucleares/efectos de los fármacos , Receptores de Lipopolisacáridos/análisis , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/enzimología , Células Supresoras de Origen Mieloide/química , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Krüppel-like factor 8 (KLF8), a transcription factor, belongs to the KLF8 family. Currently, studies have shown that KLF8 is highly expressed in some tumors. However, the prognostic value and metastasis of KLF8 in cancers remain unclear. For the first time, we conducted meta-analysis to explore the relationship between KLF8 expression with prognosis and metastasis in various carcinomas patients. METHODS: Web of Science, PubMed, Embase, and Cochrane Library were systematically searched for eligible articles. Pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated to evaluate the prognostic value and metastasis of KLF8 expression in human cancer patients. RESULTS: The result revealed that highly expression level of KLF8 was significantly associated with poor overall survival (OS) (HRâ=â1.56, 95% CI: 1.26-1.87). Meanwhile, this significant correlation was also observed in subgroup analysis stratified by cancer types, source of HR, sample size, follow-up (months). In addition, highly expression of KLF8 was also closely associated with metastasis (HRâ=â1.37, 95% CI: 0.57-2.17) and tumor node metastasis stage (HRâ=â1.58, 95% CI: 0.90-2.25) in carcinomas. CONCLUSION: In summary, our meta-analysis indicates that overexpression of KLF8 may be associated with poor prognosis and higher incidence of metastasis in various carcinomas, and KLF8 may be used as a prognostic and metastatic indicator in human cancers.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma/genética , Metástasis de la Neoplasia/genética , Proteínas Represoras/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Factores de Transcripción de Tipo Kruppel , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
Long non-coding RNAs (lncRNAs) have been demonstrated that they not only play important roles in tumorgenicity but also associate with cancer prognosis. Recently, highly up-regulated in liver cancer (HULC) is abnormally expressed in liver cancer and other cancers, and participated in cancers progression; however, it is unclear whether its expression is associated with prognosis. Here, we performed a meta-analysis and systematic review to evaluate the prognostic value and metastasis of HULC in various cancer patients. The meta-analysis was performed using a systematic search of PubMed, Web of Science, ScienceDirect and Wiley Online Library database to eligible studies. The pooled hazard ratios (HRs) with a 95% confidence interval (95% CI) were calculated to assess its prognosis and metastasis in human cancer. A total of 1134 patients from 11 studies were included. The results indicated that overexpression of HULC was associated with poor overall survival (OS) (HR = 1.89, 95% CI: 1.32-2.47). Furthermore, subgroup analysis showed that cancer type (digestive system cancer or non-digestive system cancers) and sample size (more or less than 100) significantly associated between HULC and OS. In addition, overexpression of HULC expression was significantly associated with metastasis in cancers (HR = 2.67, 95% CI: 0.94-4.39). The meta-analysis indicated that lncRNA HULC could serve as a new molecular marker for cancer prognosis and metastasis.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias/genética , Neoplasias/patología , ARN Largo no Codificante/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis de la Neoplasia , PronósticoRESUMEN
The Philadelphia (Ph; BCR-ABL) chromosome originates from a translocation event between chromosomes 9 and 22, and results in the BCR-ABL fusion gene. In chronic myelogenous leukemia (CML), the BCR-ABL gene is mainly coded for by a major breakpoint cluster region (M-bcr, e13a2 and e14a2). However, in some patients, BCR-ABL genes are encoded by a minor (m)-bcr, e1a2, and a micro (µ)-bcr region, e19a2. These transcripts revealed a different clinical course. The present study described a CML patient whose cytogenetics and FISH analyses of bone marrow revealed a karyotype of 46, XY t(9,22) (q34;q11), while the commercial kits of quantitative PCR (qPCR) failed to detect the BCR-ABL fusion gene. Further multiplex Reverse transcription-PCR (RT-PCR) and sequencing analyses identified a rare e14a3 (b3a3) fusion transcript.