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Objective@#To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR).@*Methods@#The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring.@*Results@#There were 39 males (57.4%) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%; χ2 = 9.249, P = 0.002); the 2-year relapse-free survival (RFS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (13.2% vs. 48.7%; χ2 = 9.249, P = 0.002); the 2-year overall survival (OS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (58.0% vs. 100%; χ2 = 4.122, P = 0.042). Up to follow-up date, 3 patients with molecular MRD positive and 1 patient with molecular MRD negative who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still in disease-free survival. The results of monitoring MRD showed high consistency (76.7%, 33/43) in NGS and MFC. Compared with the other groups, the patients with both positive NGS and MFC had a higher relapse rate, and the difference was statistically significantly (P < 0.05).@*Conclusions@#Molecular MRD of AML patients is detected by using NGS technology, which could be used to predict the relapse and survival, suggesting that molecular MRD may guide post-remission treatment regimens and the determination of allo-HSCT indications.
ABSTRACT
Objective To investigate the value of next-generation sequencing (NGS) technology in the prognosis monitoring and treatment guidance for molecular minimal residual disease (MRD) in acute myeloid leukemia (AML) patients with complete remission (CR). Methods The clinical data of 68 AML (non-acute promyelocytic leukemia) patients who received gene mutation spectrum by using NGS technology at initial diagnosis and in CR phase in Tangdu Hospital of Air Force Military Medical University from January 2016 to July 2018 were retrospectively analyzed. The recurrence and survival of both molecular MRD positive group and negative group were analyzed and compared, and the value of NGS technology and multiparameter flow cytometry (MFC) were also analyzed in MRD monitoring. Results There were 39 males (57.4% ) and 29 females (42.6%) in 68 patients, and the median age was 52 years old (8-82 years old). Molecular MRD positive group included 38 patients, while negative group included 30 patients. Residual mutation gene type in CR phase was most frequently detected in epigenetic regulator gene mutations, such as ASXL1, TET2, DNMT3A and IDH1/IDH2. Statistical analysis showed that the 2-year cumulative recurrence rate (CIR) in the molecular MRD positive group was higher than that in the molecular MRD negative group (86.8% vs. 51.3%;χ 2＝ 9.249, P＝ 0.002); the 2-year relapse-free survival (RFS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (13.2% vs. 48.7%; χ2＝ 9.249, P＝ 0.002); the 2-year overall survival (OS) rate in the molecular MRD positive group was lower than that in the molecular MRD negative group (58.0% vs. 100%; χ 2 ＝ 4.122, P＝ 0.042). Up to follow-up date, 3 patients with molecular MRD positive and 1 patient with molecular MRD negative who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) were still in disease-free survival. The results of monitoring MRD showed high consistency (76.7%, 33/43) in NGS and MFC. Compared with the other groups, the patients with both positive NGS and MFC had a higher relapse rate, and the difference was statistically significantly (P < 0.05). Conclusions Molecular MRD of AML patients is detected by using NGS technology, which could be used to predict the relapse and survival, suggesting that molecular MRD may guide post-remission treatment regimens and the determination of allo-HSCT indications.
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Objective To investigate the expression of long-chain non-coding RNA gastric cancer high expression transcription factor 1 (GHET1) in hepatocellular carcinoma (HCC) and the correlation with prognosis,cell proliferation,migration and invasion.Methods 20 HCC patients who underwent surgery from Fuzhou General Hospital of Chinese People's Liberation Army from March to May 2016 were included.The HCC tissue and adjacent normal tissue of 182 patients from June 2012 to December 2013 were retrospectively collected.According to the median value of GHET1 expression,it was divided into GHET1 high expression group and low expression group,91 cases each.Huh7 and HepG2 cells were divided into:blank control group (Con) with serum-free medium,siRNA-GHET1 group transfected with siRNA-GHET1,and negative control group (siRNA-NC) transfected with negative control sequence.The expression of GHET1 was detected by real-time fluorescence quantitative polymerase chain reaction,and the effect of GHET1 on HCC cells was analyzed by CCK-8,Transwell assay and Western blot.Results Compared with adjacent normal tissue,the relative expression of GHET1 mRNA in HCC tissues was significantly increased.Compared with LO2 cells,the mRNA expression of GHET1 in Huh7 and HepG2 cells was higher (P＜0.05).The GHET1 high expression group had tumor＞5 cm,vascular invasion,AFP＞400 μg/L,Edmonson grade Ⅰ,and the tumor-free ratio was lower in the expression group (P＜0.05).Survival analysis showed that HCC patients with high GHET1 expression had a poorer prognosis than patients with low expression.Multivariate Cox regression analysis showed that high expressed GHET1,vascular invasion (HR=2.067,95％ CI:1.350 to 3.162),and without tumor capsule are independent predictors of recurrence in HCC patients.After transfection with Huh7 and HepG2 cells,the proliferation of siRNA-GHET1 group was significantly decreased comparing with Con and siRNA-NC groups.Compared with siRNA-NC group,the migration and invasion ability of siRNA-GHET1 group decreased,and E-cadherin expression increased.The expression of fibronectin and vimentin decreased,and the difference was statistically significant (P＜0.05).Conclusions The expression of GHET1 in HCC tissue is higher comparing with normal tissue,which increases the proliferation,migration and invasion of hepatoma cells.It is an independent predictor of prognosis in HCC patients and a potential target for clinical treatment.
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Objective To explore the effects of H 2 S on neuronal injuries induced by oxygen glucose deprivation /reoxygenation ( OGD/R) in cortical neurons .Methods For OGD, the primary cultured cortical neurons were incubated with glucose-free EBSS media for 4h in N2/CO2/O2 (93%/5%/2%) atmosphere.Thereafter, the media were replaced by Neurobasal/B27 culture media and the neurons were incubated for 12 h in a 5%CO2 incubator at 37℃.NaHS was used as a H2S donor and cell survival rate was determined by cell counting kit 8(CCk-8).[Ca2+]i was determined using fura-2/AM and fluorescence microscopic imaging systems .The release rate of lactate dehydrogenase ( LDH) was determined by lactate dehydrogenase assay kit , and cell damage was analyzed by staining of propidium iodide ( PI ) .Results After pretreated with 200, 300 and 600μmol/L sodium hydrosulfide ( NaHS) for 30min before OGD/R, the cell survival rate of neurons significantly increased (n=4).[Ca2+]I(n=5), LDH release rate (n=4) and cell damage percentage (n=6) in the neuron pretreated with 300 μM NaHS were significantly lower than those in ODG/R cells.Treatment with 10μmol/L calcium chelator BAPTA also reduced the LDH release rate and cell damage percentage induced by ODG /R in neurons . Conclusion The results indicate that H 2 S may inhibit the OGD/R induced damage in cortical neurons via reducing calcium overload of neurons .