ABSTRACT
BACKGROUND: The runt-related transcription factor family (RUNXs) including RUNX1, RUNX2, and RUNX3 are key transcriptional regulators in normal hematopoiesis. RUNXs dysregulations caused by aberrant expression or mutation are frequently seen in various human cancers especially in acute myeloid leukemia (AML). OBJECTIVE: We systemically analyzed the expression of RUNXs and their relationship with clinic-pathological features and prognosis in AML patients. METHODS: Expression of RUNXs was analyzed between AML patients and normal controls from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) projects. Correlations between RUNXs expression and clinical features together with survival were further analyzed. RESULTS: All RUNXs expression in AML patients was significantly increased as compared with controls. RUNXs expression was found to be significantly associated with genetic abnormalities such as RUNX1 mutation, t(8;21) and inv(16)/t(16;16). By Kaplan-Meier analysis, only RUNX3 overexpression was associated with shorter overall survival (OS) and disease-free survival (DFS) among non-M3 AML patients. Notably, in high RUNX3 expression groups, patients received hematopoietic stem cell transplantation (HSCT) had markedly better OS and DFS than patients without HSCT among both all AML and non-M3 AML. In low RUNX3 expression groups, there were no significant differences in OS and DFS between HSCT and non-HSCT groups among both all AML and non-M3 AML. In addition, a total of 835 differentially expressed genes and 69 differentially expressed microRNAs were identified to be correlated with RUNX3 expression in AML. CONCLUSION: RUNXs overexpression was a frequent event in AML, and was closely associated with diverse genetic alterations. Moreover, RUNX3 expression may be associated with clinical outcome, and helpful for guiding treatment choice between HSCT and chemotherapy in AML.
Subject(s)
Core Binding Factor Alpha 3 Subunit/metabolism , Gene Expression Regulation, Leukemic , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/genetics , Neoplasm Recurrence, Local/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Bone Marrow/pathology , Case-Control Studies , Chromosomes, Human, Pair 16/genetics , Chromosomes, Human, Pair 8/genetics , Core Binding Factor Alpha 2 Subunit/genetics , DNA Methylation , Datasets as Topic , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Mutation , Neoplasm Recurrence, Local/genetics , Prognosis , Translocation, Genetic , Young AdultABSTRACT
TET family members (TETs) encode proteins that represent crucial factors in the active DNA demethylation pathway. Evidence has proved that TET2 mutation is associated with leukemogenesis, drug response, and prognosis in acute myeloid leukemia (AML). However, few studies revealed the TETs expression and its clinical significance in AML. We conducted a detailed expression and prognosis analysis of TETs expression in human AML cell lines and patients by using public databases. We observed that TETs expression especially TET2 and TET3 was closely associated with AML among various human cancers. TET1 expression was significantly reduced in AML patients, whereas TET2 and TET3 expression was significantly increased. Kaplan-Meier analysis showed that only TET3 expression was associated with overall survival (OS) and disease-free survival (DFS) among both total AML as well as non-M3 AML, and was confirmed by another independent cohort. Moreover, Cox regression analysis revealed that TET3 expression may act as an independent prognostic factor for OS and DFS in total AML. Interestingly, patients that received hematopoietic stem cell transplantation (HSCT) did not show significantly longer OS and DFS than those who did not receive HSCT in TET3 high-expressed groups; whereas, in TET3 low-expressed groups, patients that accepted HSCT showed significantly longer OS and DFS than those who did not accept HSCT. By bioinformatics analysis, TET3 expression was found positively correlated with tumor suppressor gene including CDKN2B, ZIC2, miR-196a, and negatively correlated with oncogenes such as PAX2 and IL2RA. Our study demonstrated that TETs showed significant expression differences in AML, and TET3 expression acted as a potential prognostic biomarker in AML, which may guide treatment choice between chemotherapy and HSCT.
Subject(s)
DNA-Binding Proteins/genetics , Dioxygenases/genetics , Gene Expression Regulation, Neoplastic , Leukemia, Myeloid, Acute/genetics , Mixed Function Oxygenases/genetics , Proto-Oncogene Proteins/genetics , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/genetics , Cohort Studies , Disease-Free Survival , Female , Hematopoietic Stem Cell Transplantation , Humans , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Prognosis , RNA, Messenger/genetics , Young AdultABSTRACT
The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in water, suspended particulate matters (SPMs), and sediments in the Lanzhou reach of the Yellow River were investigated in this study. The total PAH concentrations ranged from 548 to 2598 ng/L in water, 1502 to 11,562 ng/g in SPMs, and 181 to 1583 ng/g in sediments. The compositions of PAHs showed that 2- to 3-ring PAHs were abundant in water, 2- to 4-ring PAHs were predominant in SPMs, and 2- to 5-ring PAHs were abundant in sediments. The spatial distribution of PAHs was site-specific and PAHs varied at different sampling locations. The diagnostic ratio analysis indicated that the PAHs mainly had a pyrolytic source. The ecological risk assessment showed that the ecosystem risk of PAHs was low in the Lanzhou reach of the Yellow River.