Low Expression Of BCL11B Predicts Poor Overall Survival In Adult Standard Risk T-ALL

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1362-1362
Author(s):  
Isabelle Bartram ◽  
Nicola Gökbuget ◽  
Cornelia Schlee ◽  
Sandra Heesch ◽  
Lars Fransecky ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Poor Prognosis ◽  
Clinical Characteristics ◽  
Risk Group ◽  
High Expression ◽  
Prognostic Impact ◽  
Expression Levels ◽  
Standard Risk ◽  
Low Expression

Abstract Introduction Although risk stratification, detection of minimal residual disease (MRD) and implementation of novel therapeutic agents have improved outcome in acute lymphoblastic leukemia (ALL), survival in adult T-ALL patients still remains unsatisfactory. Therefore, new prognostic markers and potential therapeutic targets are warranted. BCL11B, a key player in normal T-cell development, has recently gained interest due to its high mutation rate (9-16%) in T-ALL. We investigated the frequency of BCL11B mutations, expression levels and the prognostic value in a large uniformly treated cohort of adult T-ALL. Patients and methods We analyzed bone marrow (BM) samples of 201 adult T-ALL patients sent to the reference laboratory of the German Multicenter Study Group for Adult ALL (GMALL). BCL11B expression was determined in 195 patients by qRT-PCR, BCL11B mutations were assessed in 178 patients by Sanger sequencing of exon 4 (including all 6 zink finger [ZF] domains). Low expression of BCL11B was defined by expression levels in the lowest quartile (BCL11Blow), high expression by levels in the three remaining quartiles (BCL11Bhigh). Samples had previously been characterized for expression of BAALC, IGFBP7, MN1, WT1, GATA3, ERG as well as for the mutations status of NOTCH1, WT1, and TCR rearrangements. Clinical data were available for 169 patients enrolled on the GMALL trials. We generated BCL11B associated gene expression profiles (GEP) derived from an independent set of 86 T-ALL patients enrolled in the Microarrays Innovations in LEukemia multicenter study. Results BCL11B was aberrantly expressed in adult T-ALL with significantly higher expression levels in thymic compared to early T-ALL (0.6 vs. 0.3, P=0.01). Expression of genes associated with a prognostic impact (BAALC, IGFBP7, ERG) or/and T-cell stage dependent expression profile (GATA3, IGFBP7) showed that BCL11Blow (n=49) had higher MN1 (1.6 vs, 0.3, P=0.01), IGFBP7 (1.3 vs. 0.5, P=0.02), and lower GATA3 expression (2.1 vs. 5.7, P<0.01) compared to BCL11Bhigh patients (n=146). This maturation stage specific expression of BCL11B was stressed by a higher rate of TCR rearrangement in BCL11Bhigh patients (73% vs. 27%, P=0.005) and further underlined by the BCL11B derived GEP linking low BCL11B to an immature molecular signature characterized by high expression of BAALC, IGFBP7, FLT3, CD34. Regarding clinical characteristics, low BCL11B expression was associated with a poor prognosis (5-year overall survival (OS): low 35% (n=40) vs. high 53% (n=129), P=0.02) in the overall T-ALL cohort. In the standard risk group of thymic T-ALL (n=102), BCL11Blow identified patients with an unexpected poor outcome (5-year OS: 20%, n=18) compared to BCL11Bhigh (62%, n=84, P<0.001). In addition, BCL11Blow thymic T-ALL patients showed a lower remission rate (5 years: 38% vs. 72%, P=0.02). BCL11B mutations were found in 24 of the 178 (13.5 %) T-ALL patients. In 9 patients, mutations resulted in frame shifts, whereas the remaining, except for a single one, missense mutations were located in the ZF domains: three resulting in introduction of a stop codon. BCL11B mutations were enriched in the mature immunophenotype (thymic: 20%, mature: 8%, early: 3%, P=0.03). No differences were observed in mRNA levels for BAALC, IGFBP7, MN1, WT1, GATA3, ERG, but patients with BCL11B mutations were less frequently assigned to the BCL11Blow group compared to those with high expression (5% vs. 95%, P=0.02). Regarding the clinical characteristics, BCL11B mutations had no prognostic impact regarding OS, neither in the total T-ALL cohort (5-year OS: 56% vs. 48%, n.s.) nor in the thymic T-ALL subgroup (5-year OS: 65% vs. 51%, n.s). Conclusion Our data confirmingly show a high frequency of BCL11B mutations (13.5%) in the so far largest cohort of adult T-ALL patients. As loss of function mutations were restricted to functional ZF domains and recurrently occurred in thymic T-ALL, these data stress a potential pathogenetic role of BCL11B as T-cell specific transcription factor. Importantly, low expression was associated with poor prognosis; in particular in the standard risk group of thymic T-ALL, BCL11Blow is a novel marker that identifies patients with an unacceptable poor prognosis. These findings might help to improve risk stratification in a significant proportion of adult T-ALL patients, which fail to standard therapy despite the favourable immunophenotypic characteristics. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Family Members of Mrps Expression and significance in Childhood Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5191-5191
Author(s):  
Baoling Qiu ◽  
Dong WU ◽  
Qi Zhou ◽  
Dan Hong ◽  
Jian Pan ◽  
...  
Keyword(s):  
High Risk ◽  
Complete Remission ◽  
Risk Group ◽  
High Risk Group ◽  
High Expression ◽  
Initial Stage ◽  
High Expression Group ◽  
Standard Risk ◽  
Median Expression ◽  
Low Expression

Abstract Objective Multidrug resistance-associated proteins 1 to 6 have been reported involved in a large number of tumors and have a close correlation with tumor multi-drug resistance. In this work, we detect the MRP2-6 genes expression in childhood acute lymphoblastic leukemia (ALL) by Q-RT-PCR and explore their clinical significance. Methods 156 patients at different stages of ALL were enrolled in this study and treated by the protocol (CCLG-2008) during 2012 to 2013, including 67 cases at initial stage, 70 cases at complete remission, and 9 cases at relapse, 10 patients diagnosed as idiopathic thrombocytopenic purpura (ITP) as control. MRP1-6 genes’ expressions were detected using real-time quantitative PCR (QRT-PCR)and their clinical significance was analyzed by the SPSS software 16.0. P value below 0.05 was regarded as statistic significance. Results The median expression of MRP1 was 5.82 and 8.49 for initial and relapse group,respectively, which was statistic higher than that at complete remission, the latter was 1.99. MRP1 expression level had close correlation with ALL risk, the median of MRP1 expression was 4.28, 5.62 and 7.56 for standard-risk group (SR), intermediate-risk group (IR) and high-risk group (HR), respectively. Initial ALL children were divided into two groups including high expression group and low expression group by the median expression, the rate of sensitivity of blast cells to prednisone on 7th day was 70.6% in high expression group (n=34), which was statistic lower than that in low expression group which was 90.9% (n=33, P=0.035). The rate of complete remission on 33th day in high expression group was 64.7%, while 87.9% in low expression group, which showed a significant difference between them (P=0.026). The rate of complete remission on 15th day in high expression group was 68.8%, and 69.7% in low expression group, which showed no significance between them (P=0.664). The transcription level of MRP1 in initial group of T-ALL (median=7.71) was statistic higher than that in B-ALL (median=5.18) (P=0.007). Correlation analysis indicated that mRNA expression level of MRP1 didn’t show any relationship with gender, age, WBC count, hemoglobin, platelet and blast percentage in bone narrow and peripheral blood at diagnosis. The median expression of MRP2 at initial stage was highest, higher than that at relapse and complete remission, but did not reach statistic significance. However, the median expression of MRP3 at initial stage was highest and statistic higher than complete remission. MRP4 and MRP5 showed a similar pattern in their expression, namely, high expression for relapse, intermediate expression for initial stage and low expression at complete remission which reached statistic significance. The median expression of MRP6 for relapse was 2.003, which was higher than initial and complete remission group, but the differences among them were not significant. The median of MRP2 and MRP5 expression for intermediate-risk group (IR) (Median MRP2=4.622, Median MRP5=1.712) was higher than standard- risk group (SR) (Median MRP2=3.279, Median MRP5=1.277) and high risk group (HR) (Median MRP2=2.145, Median MRP5=1.673). However, there was no statistical significance among them. The median of MRP4 expression was increase continually with the risk of ALL, but did not reach statistical significance among them; the median of MRP6 expression for high-risk group (HR) was higher than standard-risk group (0.8812 vs 0.6205) and intermediate-risk group (0.8812 vs 0.4053), but the differences among them were not significant either. Initial ALL children were divided into two group including high expression group and low expression group by median expression, and evaluated their prediction on the treatment response on 7th, 15th and 33th day. The results revealed no significant difference between them, neither between B-ALL and T-ALL. Single factor analysis showed that MRP2 has relationship with platelet count at diagnosis and MRP4 has relationship with gender. Conclusions In children ALL, the expression of MRP1 is closely related with immunophenotyping, treatment response, hazard level and disease relapse which was a poor biomarker for ALL prognosis. MRP2-6 has a different expression pattern. MRP4 and MRP6 mRNA expression showed a close relation with relapse. Disclosures No relevant conflicts of interest to declare.

scholarly journals Prognostic significance of SDF-1 in colorectal cancer depends on CD8+ T-cell density

2020 ◽  
Author(s):  
Alexandros Lalos ◽  
Ali Tülek ◽  
Nadia Tosti ◽  
Robert Mechera ◽  
Alexander Wilhelm ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
T Cells ◽  
T Cell ◽  
Cell Density ◽  
Cd8 T Cells ◽  
Prognostic Significance ◽  
Cd8 T Cell ◽  
High Expression ◽  
Prognostic Impact

Abstract Background: Since colorectal cancer (CRC) remains one of the most common malignancies, a tremendous amount of studies keep taking place in this field. Over the past 25 years, a notable part of the scientific community has focused on the association between the immune system and colorectal cancer. A variety of studies have shown that high densities of infiltrating CD8+ T cells are associated with improved disease-free and overall survival in colorectal cancer (CRC). Stromal cell-derived factor-1 (SDF-1) is a protein that regulates leukocyte trafficking and is variably expressed in several healthy and malignant tissues. There is strong evidence that SDF-1 has a negative prognostic impact on colorectal cancer (CRC). However, based on a significant correlation of SDF-1 and CD8+ T cells in a previous study (r=0.53, p<0.0001), we hypothesized that the prognostic significance of SDF-1 in CRC could depend on the immune microenvironment. Therefore, we explored the combined prognostic significance of SDF-1 expression and CD8+ T cell density in a large CRC collective. Methods: We analyzed a tissue microarray (TMA) of 613 patient specimens of primary CRCs by immunohistochemistry (IHC) for the expression of SDF-1 by tumor cells and tumor-infiltrating immune cells (TICs) and CD8+ T-cells. Besides, we analyzed the expression of SDF-1 at the RNA level in The Cancer Genome Atlas cohort (TCGA). Results: We found that the the combined high expression of SDF-1 and CD8+ T-cell infiltration shows a favorable 5-year overall survival rate (66%; 95%CI=48–79%) compared to tumors showing a high expression of CD8+ T-cells only (55%; 95%CI=45–64%; p=0.0004). High expression of SDF-1 and CD8+ T-cells infiltration was significantly associated with a favorable prognosis also in a validation group (p=0.016). Univariate and multivariate Hazard Cox regression survival analysis considering the combination of both markers revealed that the combined high expression of SDF-1 and CD8+ T cells was an independent, favorable, prognostic marker for overall survival (HR=0.34, 95%CI=0.17–0.66; p=0.002 and HR=0.45, 95%CI=0.23–0.89; p=0.021, respectively). In a spearman’s correlation analysis from the TCGA cohort, SDF-1 also correlated significantly with CD8+ T cells (r=0.28). Conclusions: SDF-1 high /CD8 high density represents an independent, favorable, prognostic condition in CRC, most likely due to an effective antigen-specific immune response.

High Expression Levels of Iaps Predict Poor Overall Survival in Childhood De Novo Acute Myeloid Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4396-4396
Author(s):  
Ingo Tamm ◽  
Stephan Richter ◽  
Doreen Oltersdorf ◽  
Ursula Creutzig ◽  
Jochen Harbott ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
De Novo ◽  
High Expression ◽  
Prognostic Impact ◽  
Poor Overall Survival ◽  
Expression Levels ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Apoptosis-related proteins are important molecules for predicting chemotherapy response and prognosis in adult acute myeloid leukemia (AML). However, data on the expression and prognostic impact of these molecules in childhood AML are rare. Using flow cytometry and western blot analysis, we therefore investigated 45 leukemic cell samples of children with de novo AML enrolled and treated within the German AML-BFM93 study for the expression of apoptosis-regulating proteins (CD95, Bcl-2, Bax, Bcl-xL, Procaspase-3, XIAP, cIAP-1, Survivin). XIAP (p&lt;0.002) but no other apoptosis regulators showed maturation-dependent expression differences as determined by FAB morphology with the highest expression levels observed within the immature M0/1 subtypes. XIAP (p&lt;0.01) and Bcl-xL (p&lt;0.01) expression was lower in patients with favorable than intermediate/poor cytogenetics. After a mean follow-up of 34 months, a shorter overall survival was associated with high expression levels of XIAP {30 (n=10) vs. 41 months (n=34); p&lt;0.05} and Survivin {27 (n=10) vs. 41 months (n=34); p&lt;0.05}. We conclude that apoptosis-related molecules are associated with maturation stage, cytogenetic risk groups and therapy outcome in childhood de novo AML. The observed association of XIAP with immature FAB types, intermediate/poor cytogenetics and poor overall survival should be confirmed within prospective pediatric AML trials.

High Transcription Levels Of S100A8 and S100A9 In Acute Myeloid Leukemia Are Predictors For Poor Overall Survival

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2610-2610 ◽  
Author(s):  
Shao-yan Hu ◽  
Ming-ying Zhang ◽  
Shui-yan Wu ◽  
Dong Wu ◽  
Neetika Ashwani ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
De Novo ◽  
Risk Group ◽  
High Expression ◽  
Intermediate Risk ◽  
Newly Diagnosed ◽  
Transcription Level ◽  
Expression Levels ◽  
De Novo Aml ◽  
Low Expression

Abstract S100A8 and S100A9 are two members of the S100 calcium-binding protein family, preferentially form functional heterodimers of S100A8/S100A9, and have been increasingly recognized as biomarkers in malignancies. Recent proteomic studies revealed that S100A8 and S100A9 played pivotal roles in hematologic malignancies and elevated expression of S100A8/S100A9 implicated in glucocorticoid resistance in MLL-rearranged infant acute lymphoblastic leukemia (ALL). In addition, S100A8 proteomic expression in leukemic cells was reported to predict survival in AML patients. However, information on the gene expression level of S100A8 and S100A9 and their clinical correlation in acute myeloid leukemia (AML) is lacking. Using the real-time quantitative RT-PCR, we analyze the transcription levels of S100A8 and S100A9 in AML patient leukemic specimens underwent pre-planned induction chemotherapy. A total of 189 patient cases at different stages of AML (excluding acute promyelocytic leukemia [APL]), including 91 newly diagnosed AML, 64 patient remission marrow specimens and 34 patient specimens as well as 20 controls without leukemia were included in the study collected from the period between 2007 and 2011. Among the cohort of 91 newly diagnosed AML, the over all median OS was 20 months, and the median follow-up for survivors was 24 months (range: 17 to 60 months). There were significant positive correlations of transcription levels between S100A8 and S100A9 in AML patients from different stages. The expression levels of S100A8 and S100A9 in newly diagnosed and relapsed AML patients revealed no significant difference, but were both lower than those in complete remission and control group. Patients with high transcription level of S100A8 and S100A9 were predominantly in AML with myelo-monocytic differentiation (M4, M5) whereas those with low transcription level of S100A8 and S100A9 often showed more immature cytomorphology (M0, M1), erythrocytic or megakaryocytic differentiation. The subgroup of patient with high transcription level of S100A8 could be a predictor for inferior overall survival (OS) (P = 0.0012). High levels of transcription for both S100A8 and S100A9 in de novo AML patients could predict shorter OS than those with low levels after adjustment on their ages at diagnosis (P = 0.003). In a multivariate analysis for OS, high S100A8 transcription was a significant prognostic factor (P =0.001) after analysis adjustment for age (P = 0.019), bone marrow blast percentage (P = 0.04) and cytogenetic classification (P = 0.05) at diagnosis. Using a combination of S100A8 transcription level and cytogenetic risk classification, survival analysis gave result that the new stratification was highly correlated with the OS (P < 0.0001). With significantly different OS, patients from the intermediate-risk group can be divided into two subgroups (IH = cytogenetically intermediate-risk with S100A8 high transcription and IL = cytogenetically intermediate-risk with S100A8 low transcription). Patients from group IL emerged with a probability of OS similar to the cytogenetically favorable-risk group, whereas the survival curve of IH subgroup was close to the unfavorable-risk group. (Figure)FigureRisk stratification of de novo AML patients by a combination of age and cytogenetic characteristics with S100A8 expression levels. 1H = cytogenetically favorable-risk with S100A8 high expression, 1L = cytogenetically favorable-risk with S100A8 low expression, 2H = cytogenetically intermediate-risk with S100A8 high expression, 2L = cytogenetically intermediate-risk with S100A8 low expression, 3H = cytogenetically unfavorable-risk with S100A8 high expression, 3L = cytogenetically unfavorable-risk with S100A8 low expression.Figure. Risk stratification of de novo AML patients by a combination of age and cytogenetic characteristics with S100A8 expression levels. 1H = cytogenetically favorable-risk with S100A8 high expression, 1L = cytogenetically favorable-risk with S100A8 low expression, 2H = cytogenetically intermediate-risk with S100A8 high expression, 2L = cytogenetically intermediate-risk with S100A8 low expression, 3H = cytogenetically unfavorable-risk with S100A8 high expression, 3L = cytogenetically unfavorable-risk with S100A8 low expression. In conclusion, the transcription levels of S100A8 and S100A9 were significantly associated with development and prognosis of AML. Both S100A8 and S100A9 expression levels provided useful clinical information, and more importantly, S100A8 expression level significantly correlates with prognosis in addition to well-known cytogenetic risk factors, and could potentially further refine current stratification of de novo AML patients. Disclosures: No relevant conflicts of interest to declare.

Prevalence and Prognostic Impact of CEBPA mutations in Children with AML Treated with the AIEOP-LAM 2002/01 Protocol.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2643-2643
Author(s):  
Giovanni Cazzaniga ◽  
Riccardo Masetti ◽  
Giulia Ferrari ◽  
Tiziana Coliva ◽  
Carmelo Rizzari ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Group ◽  
Prognostic Impact ◽  
Granulocytic Differentiation ◽  
Free Survival ◽  
Cebpa Mutations ◽  
The Impact ◽  
Standard Risk ◽  
Improved Outcome

Abstract Abstract 2643 Poster Board II-619 C/EBP is a transcription factor that regulates terminal granulocytic differentiation. CEBPA mutations have been associated with improved outcome in both adult and pediatric patients with acute myeloid leukemia (AML). However, the impact in different treatment protocols, as well as the different outcome between single and double mutants, is still to be definitively established. We evaluated the prevalence and prognostic significance of CEBPA mutations in children with de novo non promyelocitic AML treated in Italy with the AIEOP-LAM 2002/01 pediatric protocol. Among 205 patients enrolled in the protocol between December 2002 and December 2007, 103 were successfully analyzed for CEBPA mutations by PCR amplification of TAD and bZIP domains of the gene, and through sequencing of positive cases after DHPLC analysis. Characteristics of analyzed and non analyzed patients were not statistically different. Two types of CEBPA mutations, N-terminal (TAD) truncating mutations and in-frame bZip domain mutations, were detected in 13/103 (12.6%) patients tested; 8 of them (61.5%) harboured both mutation types. Laboratory, clinical characteristics and outcomes for patients with CEBPA mutations were compared to those of patients with wild-type CEBPA. CEBPA mutations were significantly more common in older patients (8/13 vs 30/90 children were older than 10 years), in patients with FAB M1 (7/13 vs 4/90), and in patients with normal cytogenetics (13/13). None of the CEBPA mutated cases carried either FLT3 or NPM1 mutations. Only 1 mutated case was found in Standard Risk patients (defined as children carrying isolated CBF abnormality and achieving complete remission after 1 cycle of induction therapy), while the other 12 patients belonged to the High Risk group. Although the values did not reach statistical significance because of the low prevalence of CEBPA mutations, with a median follow up of 39 months (range 4–86) the event-free survival probability at 5 years was 76.9% vs. 59.6% for children with or without CEBPA mutations, respectively. The values for Disease-Free Survival were 83.3% vs. 65.4% and those for Overall Survival were 90.0%. 66.4%, respectively. No difference in terms of outcome was found between patient with a single and those with double mutants, neither between those with TAD- and bZIP- mutations. Therefore, patients in the AIEOP-LAM 2002/01 pediatric trial carrying CEBPA mutations seem to have a lower relapse rate and improved outcome, their overall survival approaching that of children belonging to the Standard Risk group (90% vs. 97%). If confirmed in a larger cohort of patients and with longer follow-up, these data suggest that CEBPA mutation analysis could be usefully employed to identify patients at lower risk of treatment failure and for allocating them into different classes of risk. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Association of JMJD2B and Hypoxia-Inducible Factor 1 Expressions with Poor Prognosis in Osteosarcoma

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Xujian Liu ◽  
Qianqian Zhang ◽  
Yi Zhao ◽  
Jianjun Xun ◽  
Hongzeng Wu ◽  
...  
Keyword(s):  
Overall Survival ◽  
Poor Prognosis ◽  
Clinical Characteristics ◽  
Malignant Tumors ◽  
Univariate Analysis ◽  
Hypoxia Inducible Factor ◽  
Prognostic Significance ◽  
Expression Levels ◽  
Hypoxia Inducible Factor 1 ◽  
Enneking Stage

Background. JMJD2B has been reported to be implicated in malignant tumors. This study is aimed at exploring the expression and prognostic significance of JMJD2B in osteosarcoma and its association with hypoxia-inducible factor 1 (HIF1). Methods. The histopathological and clinical characteristics were retrospectively reviewed from 53 osteosarcoma patients. JMJD2B and HIF1 were examined by immunohistochemical staining of paraffin-embedded osteosarcoma samples, and their association with clinical characteristics was examined by Spearman’s test. Overall survival was examined by Kaplan-Meier analysis, and prognostic factors were identified by univariate and multivariate regression analyses. Results. JMJD2B and HIF1 expression levels were both significantly associated with Enneking stage, distant metastasis, and neoadjuvant chemotherapy, and the JMJD2B and HIF1 expressions were positively correlated (p<0.001, R=0.752). In addition, univariate analysis showed that the expression of both JMJD2B and HIF1 was significantly associated with overall survival, but multivariate analysis showed that only JMJD2B expression was significantly associated with overall survival in osteosarcoma patients. Conclusions. JMJD2B and HIF1 expression levels show significant correlation with osteosarcoma progression, and JMJD2B could predict poor prognosis of osteosarcoma patients.

The prognostic importance of VEGF-A, PDGF-BB and c-MET in patients with metastatic colorectal cancer

2020 ◽  
Vol 26 (8) ◽  
pp. 1878-1885
Author(s):  
Mevlude Inanc ◽  
Hatice Aslan Sirakaya ◽  
Hatice Karaman ◽  
Oktay Bozkurt
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Progression Free Survival ◽  
High Expression ◽  
Free Survival ◽  
Expression Levels ◽  
Prognostic Importance ◽  
Low Expression

Introduction We aimed to assess the effect of VEGF-A, PDGF-BB, and c-Met expression levels on survival in patients with metastatic colorectal cancer receiving bevacizumab therapies. Patients and methods A total of 105 patients diagnosed with metastatic colorectal cancer between the years 2006 and 2016 were included in the research retrospectively. Results The progression-free survival (PFS) durations of patients with high expression levels of VEGF-A and with low expression levels of VEGF-A were 11 months and 10 months (p = 0.44), respectively. The PFS durations of patients with high PDGF-BB expression and low PDGF-BB expression were 12 months and 10 months (p = 0.16), respectively, while the PFS durations of patients with high and low c-Met expression were 8 months and 13 months (p = 0.005), respectively. Metastatic overall survival was 27 months and 18 months (p = 0.05) in patients with high and low VEGF-A expression levels, respectively, 31 months and 21 months (p = 0.16) in patients with high and low PDGF-BB expression levels, respectively, and 21 months and 26 months (p = 0.11) in patients with high and low c-Met expression levels, respectively. Conclusion The results of this research revealed a high c-Met expression relationship with worse PFS and low VEGF-A expression associated with poor metastatic overall survival in patients with metastatic colorectal cancer receiving bevacizumab therapies.

scholarly journals Expression and Prognostic Impact of FZDs in Pancreatic Adenocarcinoma

2020 ◽  
Author(s):  
Yang Li ◽  
Zirong Liu ◽  
Yamin Zhang
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathway ◽  
Pancreatic Adenocarcinoma ◽  
Critical Role ◽  
Wnt Signaling Pathway ◽  
High Expression ◽  
Prognostic Impact ◽  
Expression Levels ◽  
Significant Difference ◽  
Low Expression

Abstract Background: Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. we aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management.Methods: PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), Human Protein Atlas (HPA), Kaplan-Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (x64 3.6.2) were used to comprehensively analyze the roles of FZDs. p-value below to 0.05 was considered as significant difference.Results: In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. PAAD patients with high expression of FZD6 had shorter overall survival (OS) than those with low expression, indicating that FZD6 could be a potential prognostic and predictive marker in PAAD. PAAD patients with high expression of FZD8 had shorter recurrence free survival (RFS) than those with low expression, indicating that FZD8 could be a potential therapeutic target in PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. Conclusions: Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3, 4, 5, 6, and 9 could be potential prognostic and predictive markers, and FZD4 and 8 might function as potential therapeutic targets in PAAD.

scholarly journals Low expression of NSD1, NSD2, and NSD3 define a subset of human papillomavirus-positive oral squamous carcinomas with unfavorable prognosis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Steven F. Gameiro ◽  
Farhad Ghasemi ◽  
Peter Y. F. Zeng ◽  
Neil Mundi ◽  
Christopher J. Howlett ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Relative Level ◽  
Expression Levels ◽  
T Cell Infiltration ◽  
Molecular Features ◽  
Platinum Based Chemotherapy ◽  
Low Expression

Abstract Background Frequent mutations in the nuclear receptor binding SET domain protein 1 (NSD1) gene have been observed in head and neck squamous cell carcinomas (HNSCC). NSD1 encodes a histone 3 lysine-36 methyltransferase. NSD1 mutations are correlated with improved clinical outcomes and increased sensitivity to platinum-based chemotherapy agents in human papillomavirus-negative (HPV-) tumors, despite weak T-cell infiltration. However, the role of NSD1 and related family members NSD2 and NSD3 in human papillomavirus-positive (HPV+) HNSCC is unclear. Methods Using data from over 500 HNSCC patients from The Cancer Genome Atlas (TCGA), we compared the relative level of mRNA expression of NSD1, NSD2, and NSD3 in HPV+ and HPV- HNSCC. Correlation analyses were performed between T-cell infiltration and the relative level of expression of NSD1, NSD2, and NSD3 mRNA in HPV+ and HPV- HNSCC. In addition, overall survival outcomes were compared for both the HPV+ and HPV- subsets of patients based on stratification by NSD1, NSD2, and NSD3 expression levels. Results Expression levels of NSD1, NSD2 or NSD3 were not correlated with altered lymphocyte infiltration in HPV+ HNSCC. More importantly, low expression of NSD1, NSD2, or NSD3 correlated with significantly reduced overall patient survival in HPV+, but not HPV- HNSCC. Conclusion These results starkly illustrate the contrast in molecular features between HPV+ and HPV- HNSCC tumors and suggest that NSD1, NSD2, and NSD3 expression levels should be further investigated as novel clinical metrics for improved prognostication and patient stratification in HPV+ HNSCC.

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