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1.
Bone Marrow Transplant ; 56(1): 91-100, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32581286

RESUMO

Relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (r/r Ph+ ALL) has an extremely poor prognosis. Chimeric antigen receptor T-cell (CART) therapy has acquired unprecedented efficacy in B-cell malignancies, but its role in the long-term survival of r/r Ph+ ALL patients is unclear. We analyzed the effect of CART on 56 adults with r/r Ph+ ALL who accepted split doses of humanized CD19-targeted CART after lymphodepleting chemotherapy. 51/56 (91.1%) achieved complete remission (CR) or CR with inadequate count recovery (CRi), including 38 patients with negative minimal residual disease (MRD) tested by bone marrow BCR-ABL1 copies. Subsequently, 30/51 CR/CRi patients accepted consolidative allogeneic haematopoietic stem cell transplantation (alloHSCT). Their outcomes were compared with those of 21/51 contemporaneous patients without alloHSCT. The 2-year overall survival (OS) and leukemia-free survival (LFS) of CR/CRi patients with alloHSCT were significantly superior to those without alloHSCT (58.9%, CI 49.8-68.0% vs. 22.7%, CI 12.7-32.7%, p = 0.005; 53.2%, CI 43.6-62.8% vs. 18.8%, CI 9.2-28.4%, p = 0.000, respectively). Multivariate analysis revealed that alloHSCT and MRD-negative post-CART were the independent prognostic factors for OS and LFS. CART therapy is highly effective for r/r Ph+ ALL patients, and consolidative alloHSCT could prolong their OS and LFS.

2.
Bioengineered ; 12(1): 208-224, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33315534

RESUMO

The screening and treatment of laryngeal squamous cell carcinoma (LSCC) still perplexes clinicians, making it necessary to explore new markers. To this end, this research examined the underlying molecular mechanism of LSCC based on high-throughput datasets (n = 249) from multiple databases. It also identified transcription factors (TFs) independently associated with LSCC prognosis. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, differential expression genes of LSCC were deemed relevant to the extracellular matrix and its related structures or pathways, suggesting that the extracellular matrix plays an important role in LSCC. At the same time, several hub genes that may also have important roles in LSCC were identified via protein-protein interaction analysis, including CDC45, TPX2, AURKA, KIF2C, NUF, MUC1, MUC7, MUC4, MUC15, and MUC21. Eight unreported LSCC prognostic TFs - BCAT1, CHD4, FOXA2, GATA6, HNF1A, HOXB13, MAFF, and TCF4 - were screened via Kaplan-Meier curves. Cox analysis determined for the first time that HOXB13 expression and gender were independently associated with LSCC prognosis. Compared to control tissues, elevated expression of HOXB13 was found in LSCC tissues (standardized mean difference = 0.44, 95% confidence interval [0.13-0.76]). HOXB13 expression also makes it feasible to screen LSCC from non-LSCC (area under the curve = 0.77), and HOXB13 may play an essential role in LSCC by regulating HOXB7. In conclusion, HOXB13 may be a novel marker for LSCC clinical screening and treatment.

3.
Eur J Neurol ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33377242

RESUMO

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a clinical imaging syndrome with diverse etiology. Total homocysteine (HCY) level might increase the risk of myocardial and cerebral infarction by damaging the vascular endothelium. We aimed to explore the correlation between total HCY and CSVD imaging burden, based on Mendelian randomization methods. METHODS: A total of 1,023 participants of the Shunyi study, a population-based cohort study, were included. Vascular risk factors, total HCY levels and methylenetetrahydrofolate reductase (MTHFR) gene mutations (C677T and A1298C) were examined. CSVD imaging markers, including lacunes, cerebral microbleeds, white matter hyperintensity, enlarged perivascular space and brain parenchymal fraction (BPF) were also assessed. RESULTS: Mutations of C677T were significantly correlated with increased total HCY levels (CC→TT: ß = 0.28, p < 0.0001), while mutations of A1298C were correlated with decreased total HCY levels (AA→AC: ß = -0.13, p < 0.0001; AA→CC: ß = -0.25, p = 0.004). In the Mendelian randomization study, the C677T genotype was significantly associated with lacunes (CC→CT: odds ratio [OR] 2.76, p = 0.008; CC→TT: OR 2.50, p = 0.018), and the A1298C genotype was significantly correlated with BPF (AA→CC: ß = 1.32, p = 0.015). Similarly, in multivariate regression analysis, total HCY levels were significantly correlated with lacunes (OR 2.14, p < 0.0001) and negatively correlated with BPF (ß = -0.55, p = 0.004). Age, sex and vascular risk factors were adjusted for. CONCLUSIONS: Total HCY level was correlated with imaging burden of CSVD, especially with lacunes and brain volume loss. For individuals with risk genetic predisposition, enhanced homocysteine-lowering strategies might be necessary to reduce the risk and progress of CSVD.

4.
Med Sci Monit ; 26: e928185, 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33361747

RESUMO

BACKGROUND Immune-related genes (IRGs) are closely related to the incidence and progression of tumors, potentially indicating that IRGs play an important role in laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS An RNA sequencing dataset containing 123 samples was collected from The Cancer Genome Atlas. Based on immune-related differentially expressed genes (IRDEGs), a potential molecular mechanism of LSCC was explored through analysis of information in the Gene Ontology (GO) resource and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPIs). A regulatory network of transcriptional regulators and IRDEGs was constructed to explore the underlying molecular mechanism of LSCC at the upstream level. Candidates from IRDEGs for signature were screened via univariate Cox analysis and using the least absolute shrinkage and selection operator (LASSO) technique. The IRDEG signature of LSCC was constructed by using a multivariate Cox proportional hazards model. RESULTS GO and KEGG analysis showed that IRDEGs may participate in the progression of LSCC through immune-related reactions. PPI analysis demonstrated that, among the IRDEGs in LSCC, the Kininogen 1; C-X-X motif chemokine ligand 10; elastase, neutrophil expressed; and LYZ genes are hub genes in the development of LSCC. At the upstream level, SPI1, SP140, signal transducer and activator of transcription 4, zinc finger E-box binding homeobox, and Ikaros family zinc finger 2 are the hub transcriptional regulators of IRDEGs. The risk score based on the IRDEG signature was able to distinguish prognosis in patients with LSCC and represents an independent prognostic risk factor for LSCC. CONCLUSIONS From the perspective of IRGs, we first constructed an IRDEG signature related to the prognosis of LSCC, which can be used as a novel marker to predict prognosis in patients with LSCC.

5.
J Int Med Res ; 48(11): 300060520965791, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33203278

RESUMO

OBJECTIVE: To assess the prevalence, associated factors and cardiocerebral vascular prognosis of anaemia in patients undergoing haemodialysis. METHODS: This multicentre, retrospective, observational cohort study included patients on maintenance haemodialysis in South Guangdong, China. Anaemia in haemodialysis was defined as haemoglobin (Hb) <90 g/l. A proportion of patients were enrolled in a follow-up of the cardiocerebral vascular prognosis. RESULTS: A total of 1161 patients were enrolled and 938 were followed-up for cardiocerebral vascular events. Of 1161 patients, 250 (21.5%) had anaemia and 524 (45.1%) had an Hb level of 100-120 g/l. Adjusted multivariate logistic regression analysis demonstrated that frequency of dialysis ≤ twice weekly, hypoalbuminaemia and use of unfractionated heparin were independent factors associated with anaemia. Kaplan-Meier survival curve analysis for no myocardial infarction was 100%, 100%, 100% and 100% after 3, 6, 9 and 12 months, respectively, in patients with Hb < 90 g/l; compared with 97%, 95%, 93% and 93%, respectively, in patients with Hb ≥ 130 g/l. Adjusted Cox proportional hazards regression demonstrated that Hb ≥ 130 g/l was an independent risk factor for myocardial infarction. CONCLUSION: Anaemia is highly prevalent among patients undergoing haemodialysis in South Guangdong and requires careful management.

6.
Cell Death Dis ; 11(11): 997, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219204

RESUMO

The potential mechanism of myelodysplastic syndromes (MDS) progressing to acute myeloid leukemia (AML) remains poorly elucidated. It has been proved that epigenetic alterations play crucial roles in the pathogenesis of cancer progression including MDS. However, fewer studies explored the whole-genome methylation alterations during MDS progression. Reduced representation bisulfite sequencing was conducted in four paired MDS/secondary AML (MDS/sAML) patients and intended to explore the underlying methylation-associated epigenetic drivers in MDS progression. In four paired MDS/sAML patients, cases at sAML stage exhibited significantly increased methylation level as compared with the matched MDS stage. A total of 1090 differentially methylated fragments (DMFs) (441 hypermethylated and 649 hypomethylated) were identified involving in MDS pathogenesis, whereas 103 DMFs (96 hypermethylated and 7 hypomethylated) were involved in MDS progression. Targeted bisulfite sequencing further identified that aberrant GFRA1, IRX1, NPY, and ZNF300 methylation were frequent events in an additional group of de novo MDS and AML patients, of which only ZNF300 methylation was associated with ZNF300 expression. Subsequently, ZNF300 hypermethylation in larger cohorts of de novo MDS and AML patients was confirmed by real-time quantitative methylation-specific PCR. It was illustrated that ZNF300 methylation could act as a potential biomarker for the diagnosis and prognosis in MDS and AML patients. Functional experiments demonstrated the anti-proliferative and pro-apoptotic role of ZNF300 overexpression in MDS-derived AML cell-line SKM-1. Collectively, genome-wide DNA hypermethylation were frequent events during MDS progression. Among these changes, ZNF300 methylation, a regulator of ZNF300 expression, acted as an epigenetic driver in MDS progression. These findings provided a theoretical basis for the usage of demethylation drugs in MDS patients against disease progression.

7.
Med Sci Monit ; 26: e926273, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33104528

RESUMO

BACKGROUND Bladder carcinoma (BLCA) is a leading cause of cancer-related deaths worldwide. The aim of this work was to develop an accurate stratification in predicting the prognosis and directing the treatment of BLCA patients based on small nucleolar RNAs (snoRNAs). MATERIAL AND METHODS Expression profiles of snoRNAs were downloaded from the SNORic database. The expression profiles and clinical outcomes of BLCA patients were analyzed. Survival-associated snoRNAs were identified and used to develop a novel risk score classifier. Genes in the whole genome that were significantly correlated with the included prognostic snoRNAs were used for functional enrichment analysis. RESULTS The results showed that age, American Joint Committee on Cancer (AJCC) stage, and tumor status were significantly correlated with overall survival (OS) of BLCA patients. We selected 12 survival-associated snoRNAs to build a prognostic signature. Patients were separated into high- and low-risk groups based on the median value of the risk score. Patients in the high-risk group and low-risk group have distinct clinical outcomes. The AJCC TNM stage showed moderate utility as a prognostic indicator for clinical outcome prediction. Then, clinical parameters and risk scores were entered in multivariate Cox analysis. Notably, the prognostic signature remained an independent significant prognostic risk factor. The pathway analysis suggested that these genes were enriched in several types of cancer and "Focal adhesion" pathways. CONCLUSIONS The prognostic signature defined by expression profiles of 12 survival-associated snoRNAs appears to be an excellent predictor of the clinical outcome of BLCA patients.

8.
Insect Sci ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089948

RESUMO

In insects, 20-hydroxyecdysone (20E) limits systemic growth by triggering developmental transitions. Previous studies have shown that 20E-induced let-7 exhibits crosstalk with the cell cycle. Here, we examined the underlying molecular mechanisms and physiological functions of 20E-induced let-7 in the fat body, an organ for energy storage and nutrient mobilization which plays a critical role in the larval growth. First, the overexpression of let-7 decreased the body size and led to the reduction of both nucleolus and cell sizes in the larval fat body. In contrast, the overexpression of let-7-Sponge increased the nucleolus and cell sizes. Moreover, we found that cdc7, encoding a conserved protein kinase that controls the endocycle, is a target of let-7. Notably, the mutation of cdc7 in the fat body resulted in growth defects. Overall, our findings revealed a novel role of let-7 in the control of endoreduplication-related growth during larval-prepupal transition in Drosophila.

9.
Sci Rep ; 10(1): 18369, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110225

RESUMO

Motor impairment is common in the elderly population. Disrupted white matter tracts and the resultant loss of connectivity between cortical regions play an essential role in motor control. Using diffusion tensor imaging (DTI), we investigated the effect of white matter microstructure on upper-extremity and lower-extremity motor function in a community-based sample. A total of 766 participants (57.3 ± 9.2 years) completed the assessment of motor performance, including 3-m walking speed, 5-repeat chair-stand time, 10-repeat hand pronation-supination time, and 10-repeat finger-tapping time. Fractional anisotropy (FA), mean diffusivity (MD), and structural network connectivity parameters were calculated based on DTI. Lower FA and higher MD were associated with poor performance in walking, chair-stand, hand pronation-supination, and finger-tapping tests, independent of the presence of lacunes, white matter hyperintensities volume, and brain atrophy. Reduced network density, network strength, and global efficiency related to slower hand pronation-supination and finger-tapping, but not related to walking speed and chair-stand time. Disrupted white matter integrity and reduced cerebral network connectivity were associated with poor motor performance. Diffusion-based methods provide a more in-depth insight into the neural basis of motor dysfunction.

10.
Comput Biol Chem ; 89: 107383, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33032037

RESUMO

RUNX family transcription factor 2 (RUNX2) overexpression has been found in various human malignancies. However, the expression levels of RUNX2 mRNA and protein in lung adenocarcinoma (LUAD) were not investigated. This study aims to thoroughly analysis the expression level and potential mechanisms of RUNX2 mRNA in LUAD. We applied in-house immunohistochemistry, high-throughput RNA-sequencing, and gene microarrays to comprehensively investigate the expression level of RUNX2 in LUAD. A pool standard mean difference (SMD) and summary receiver operating characteristic curves (SROC) were calculated to assess the integrated expression value of RUNX2 in LUAD. The hazard ratios (HRs) were integrated to evaluate the overall prognostic effect of RUNX2 on the LUAD patients. The differentially expressed genes (DEGs) of LUAD, the potential target genes of RUNX2, and its co-expressed genes were overlapped to obtain a set of specific genes for GO and KEGG enrichment analyses. RUNX2 overexpression in LUAD was validated using a large number of cases (2 418 LUAD and 1 574 non-tumor lung samples). The pooled SMD was 0.85 (95 % CI: 0.64-1.05) and the area under the curve (AUC) of the SROC was 0.86 (95 %CI: 0.83-0.89). The integrated HR was 1.20 [1.04-1.38], indicating that increased expression of RUNX2 was an independent risk factor for the poor survival of the LUAD patients. RUNX2 and its transcriptionally regulates potential target genes may promote cell proliferation and drug resistance of LUAD by modulating the cell cycle and MAPK signaling pathways. RUNX2 can provide new research directions for targeted drug therapy and drug resistance for LUAD treatment.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1283-1291, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798413

RESUMO

OBJECTIVE: To analyze the effect of clinical features, routine laboratory examination and related gene mutation on the OS of patients with myelodysplastic syndrome (MDS) after hematopoietic stem cell transplantation (HSCT). METHODS: 121 patients diagnosed as MDS and underwent hematopoietic stem cell transplantation in the First Affiliated Hospital of Soochow University from October 2013 to August 2018 were selected. Basic information of the patients was collected, and blood cells, bone marrow blasts at initial diagnosis, chromosomal karyotypes and gene mutations of the patients were detected.The effect of different factors on overall survival (OS) was analyzed by statistical method. RESULTS: Kaplan-Meier univariate analysis shows that OS was significanly different among different age groups. The 3-year OS rate of patients aged 0-29 years was (83.3±7.7) %, the 3-year OS rate in patients aged 30-49 years was (58.1±7.7 %), and the 3-year OS rate of patients aged 50-69 years was (31.0±22.6) %, which was statistically different (P<0.05) between different groups. There were also significant differences in OS among patients with different transplantation types. 3-year OS rate: HLA-matched sibling HSCT>unrelated HLA-matched HSCT>haploidentical HSCT>micro HSCT. The OS rate of patients with bone marrow blasts≥10% seems lower than blasts<10%, but there was no statistical difference.The 3-year OS rate of patients with chromosomal karyotype complex abnormality was (47.7±11.5) %, and that of patients without complex abnormality was (80±4.2) % which was statistical difference (P<0.05). Patients with DNMT3A, NRAS, TP53 and GATA2 mutations had shorter OS time compared with patients without mutation of these genes, which shows statistically significant (P<0.05). COX multivariate analysis showed that age, chromosome karyotype, DNMT3A, TET2, GATA2 and NRAS were the independent factors influencing OS of patients after HSCT, with statistically significant difference. CONCLUSION: age of patients, donor selection of HSCT, chromosome karyotype, DNMT3A, NRAS, TP53, GATA2 and TET2 gene mutations are all independent factors affecting the OS of patients after HSCT. Therefore, the assessment of the OS of MDS patients with transplantation requires comprehensive consideration.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Adulto Jovem
13.
Mol Med Rep ; 22(3): 1994-2002, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32705177

RESUMO

Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines. Mutations in the TPMT gene can affect drug activity, which may have adverse effects in humans. Thus, genotyping can help elucidate genetic determinants of drug response to thiopurines and optimize the selection of drug therapies for individual patients, effectively avoiding palindromia during maintenance treatment caused by insufficient dosing and the serious side effects caused by excessive doses. The current available detection methods used for TPMT*3B and TPMT*3C are complex, costly and time­consuming. Therefore, innovative detection methods for TPMT genotyping are urgently required. The aim of the present study was to establish and optimize a simple, specific and timesaving TPMT genotyping method. Using the principles of Web­based Allele­Specific PCR and competitive real­time fluorescent allele­specific PCR (CRAS­PCR), two pairs of Scorpion primers were designed for the detection of TPMT*3B and *3C, respectively, and a mutation in TPMT*3A was inferred based on data from TPMT*3B and *3C. In total, 226 samples from volunteers living in Chongqing were used for CRAS­PCR to detect TPMT*3 mutations. Results showed that nine (3.98%) were mutant (MT) heterozygotes and none were MT homozygotes for TPMT*3C, and no TPMT*3A and TPMT*3B mutations were found. Three TPMT*3C MT heterozygotes were randomly selected for DNA sequencing, and CRAS­PCR results were consistent with the sequencing results. In conclusion, in order to improve simplicity, specificity and efficiency, the present study established and optimized CRAS­PCR assays for commonly found mutant alleles of TPMT*3A (G460A and A719G), TPMT*3B (G460A), and TPMT*3C (A719G).

14.
Biochemistry ; 59(30): 2788-2795, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32657577

RESUMO

Human neutrophil elastase (hNE) is a serine protease that plays a major role in defending the bacterial infection. However, elevated expression of hNE is reported in lung and breast cancer, among others. Moreover, hNE is a target for the treatment of cardiopulmonary diseases. Ecotin (ET) is a serine protease inhibitor present in many Gram-negative bacteria, and it plays a physiological role in inhibiting host proteases, including hNE. Despite this known interaction, the structure of the hNE-ET complex has not been reported, and the mechanism of ecotin inhibition is not available. We determined the structure of the hNE-ET complex by molecular replacement method. The structure of the hNE-ET complex revealed the presence of six interface regions comprising 50s, 60s, and 80s loops, between the ET dimer and two independent hNE monomers, which explains the high affinity of ecotin for hNE (12 pM). Notably, we observed a secondary binding site of hNE located 24 Å from the primary binding site. Comparison of the closely related trypsin-ecotin complex with our hNE-ET complex shows movement of the backbone atoms of the 80s and 50s loops by 4.6 Å, suggesting the flexibility of these loops in inhibiting a range of proteases. Through a detailed structural analysis, we demonstrate the flexibility of the hNE subsites to dock various side chains concomitant with inhibition, indicating the broad specificity of hNE against various inhibitors. These findings will aid in the design of chimeric inhibitors that target both sites of hNE and in the development of therapeutics for controlling hNE-mediated pathogenesis.

15.
J Clin Psychopharmacol ; 40(4): 359-365, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32639288

RESUMO

PURPOSE/BACKGROUND: The increased risk of type 2 diabetes mellitus (T2DM) among users of antidepressants (ADs) might be mediated by depression. We investigated whether ADs are associated with increased risk of T2DM in patients with depression. Moreover, the relationship between binding affinities of serotonin transporter (SERT) of ADs and the risk of T2DM is examined. METHODS/PROCEDURES: We conducted a retrospective nested case-control study using data from Taiwan's National Health Insurance Research Database between 2000 and 2013. A total of 3038 patients with depression, 1519 cases of T2DM, and 1519 controls matched for age, sex, and index date, were included. Exposure to ADs was categorized by type and SERT. The association between AD exposure and T2DM development was assessed using conditional logistic regression analysis. FINDINGS/RESULTS: No association between T2DM development and selective serotonin reuptake inhibitors (adjusted odds ratio [AOR], 1.01; 95% confidence interval [CI], 0.87-1.19; P = 0.962), serotonin-norepinephrine reuptake inhibitors (AOR, 1.13; 95% CI, 0.94-1.37; P = 1.196), tricyclic antidepressants (AOR, 1.01; 95% CI, 0.85-1.21; P = 0.906), or others (AOR, 0.88; 95% CI, 0.75-1.03; P = 0.104) was found. Alternatively, no association between individual ADs and potency of affinity to SERT and the risk of T2DM was found. IMPLICATIONS/CONCLUSIONS: No association between ADs and increase risk of T2DM was found in patients with depression. However, regular metabolic evaluations are recommended for patients with depression regularly taking ADs.

16.
Cancer Biomark ; 29(1): 111-124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32623386

RESUMO

Interleukin 24 (IL24) has been documented to be highly expressed in several cancers, but its role in laryngeal squamous cell carcinoma (LSCC) remains unclarified. In this study, to reveal the function and its clinical significance of IL24 in LSCC, multiple detecting methods were used comprehensively. IL24 protein expression was remarkably higher in LSCC (n= 49) than non-cancerous laryngeal controls (n= 26) as detected by in-house immunohistochemistry. Meanwhile, the IL24 mRNA expression was also evaluated based on high throughput data from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress and Oncomine databases. Consistently with the protein level, IL24 mRNA expression level was also predominantly upregulated in LSCC (n= 172) compared to non-cancerous laryngeal tissues (n= 81) with the standard mean difference (SMD) being 1.25 and the area under the curve (AUC) of the summary receiver operating characteristic (sROC) being 0.89 (95% CI = 0.86-0.92). Furthermore, the related genes of IL24 and the differentially expressed genes (DEGs) of LSCC were intersected and sent for Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) analyses. In the GO annotation, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) were extracellular matrix organization, extracellular matrix, cytokine activity, respectively. The top pathway of KEGG was ECM-receptor interaction. The PPI networks indicated the top hub genes of IL24-related genes in LSCC were SERPINE1, TGFB1, MMP1, MMP3, CSF2, and ITGA5. In conclusion, upregulating expression of IL24 may enhance the occurrence of LSCC, which owns prospect diagnostic ability and therapeutic significance in LSCC.

17.
Med Sci Monit ; 26: e922854, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32529991

RESUMO

BACKGROUND Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer worldwide, with low 5-year survival rate. To identify novel prognostic markers for OSCC and determine the immune and stromal landscape of OSCC, a risk signature for OSCC patients was constructed in this study. MATERIAL AND METHODS Immune and stromal scores for OSCC samples from the Genomic Data Commons Data Portal were computed to delineate the tumor microenvironment landscape of oral cancer based on the Estimation of STromal and Immune cells in MAlignant Tumours using Expression data algorithm. An immune score-based risk signature was constructed by combining random forest and support vector machine methods. Correlation analysis of risk signature gene expression and immune cell infiltration was conducted, and the distinguishing power of individual signature genes was evaluated by analyzing receiver operating characteristics (ROC) curves. Differentially enriched pathways between high and low risk groups were investigated via gene set variation analysis. ROC curves were plotted for signature genes to examine their ability to distinguish the recurrence and survival status of OSCC patients from GSE84846. RESULTS An immune score-related risk signature composed of ARMH1, F2RL2, AC004687.1, COL6A5, AC008750.1, RAB19, CRLF2, GRIP2, and FAM162B performed well in the prognostic stratification of OSCC patients and could effectively distinguish their survival status. Lists of pathways, including cytokine-cytokine receptor interaction and cell adhesion molecules displayed remarkable differential enrichment between high and low risk OSCC patients. CONCLUSIONS An immune score-based risk signature constructed presently may be useful to decide appropriate treatment options for individual OSCC patients.

18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(3): 717-723, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32552926

RESUMO

OBJECTIVE: To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients. METHODS: 53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing. RESULTS: 21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy. CONCLUSION: A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.


Assuntos
Leucemia Mieloide Aguda , Mutação , Cromossomos Humanos Par 11 , Transplante de Células-Tronco Hematopoéticas , Humanos , Hibridização in Situ Fluorescente , Prognóstico , Tirosina Quinase 3 Semelhante a fms
19.
PLoS One ; 15(6): e0234062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32497093

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal and malignant tumours worldwide. New therapeutic targets for HCC are urgently needed. CYCLOPS (copy number alterations yielding cancer liabilities owing to partial loss) genes have been noted to be associated with cancer-targeted therapies. Therefore, we intended to explore the effects of the CYCLOPS gene RBM17 on HCC oncogenesis to determine if it could be further used for targeted therapy. METHODS: We collected data on 12 types of cancer from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) queries for comparison with adjacent non-tumour tissues. RBM17 expression levels, clinicopathological factors and survival times were analysed. RNAseq data were downloaded from the Encyclopaedia of DNA Elements database for molecular mechanism exploration. Two representative HCC cell models were built to observe the proliferation capacity of HCC cells when RBM17 expression was inhibited by shRBM17. Cell cycle progression and apoptosis were also examined to investigate the pathogenesis of RBM17. RESULTS: Based on 6,136 clinical samples, RBM17 was markedly overexpressed in most cancers, especially HCC. Moreover, data from 442 patients revealed that high RBM17 expression levels were related to a worse prognosis. Overexpression of RBM17 was related to the iCluster1 molecular subgroup, TNM stage, and histologic grade. Pathway analysis of RNAseq data suggested that RBM17 was involved in mitosis. Further investigation revealed that the proliferation rates of HepG2 (P = 0.003) and SMMC-7721 (P = 0.030) cells were significantly reduced when RBM17 was knocked down. In addition, RBM17 knockdown also arrested the progression of the cell cycle, causing cells to halt at the G2/M phase. Increased apoptosis rates were also found in vitro. CONCLUSION: These results suggest that RBM17 is a potential therapeutic target for HCC treatment.


Assuntos
Carcinoma Hepatocelular/genética , Variações do Número de Cópias de DNA , Neoplasias Hepáticas/genética , Fatores de Processamento de RNA/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Pontos de Checagem do Ciclo Celular/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Prognóstico , Fatores de Processamento de RNA/deficiência
20.
Comput Biol Chem ; 86: 107258, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32304977

RESUMO

BACKGROUND: Thyroid carcinoma (THCA) is one of the most frequent endocrine cancers and has increasing morbidity. Annexin A2 (ANXA2) has been found to be highly expressed in various cancers; however, its expression level and potential mechanism in THCA remain unknown. This study investigated the clinicopathological value and primary molecular machinery of ANXA2 in THCA. MATERIAL AND METHODS: Public RNA-sequencing and microarray data were obtained and analyzed with ANXA2 expression in THCA and corresponding non-cancerous thyroid tissue. A Pearson correlation coefficient calculation was used for the acquisition of ANXA2 coexpressed genes, while edgR, limma, and Robust Rank Aggregation were employed for differentially expressed gene (DEG) in THCA. The probable mechanism of ANXA2 in THCA was predicted by gene ontology and pathway enrichment. A dual-luciferase reporter assay was employed to confirm the targeting relationships between ANXA2 and its predicted microRNA (miRNA). RESULTS: Expression of ANXA2 was significantly upregulated in THCA tissues with a summarized standardized mean difference of 1.09 (P < 0.0001) based on 992 THCA cases and 589 cases of normal thyroid tissue. Expression of ANXA2 was related to pathologic stage. Subsequently, 1442 genes were obtained when overlapping 4542 ANXA2 coexpressed genes with 2248 DEGs in THCA; these genes were mostly enriched in pathways of extracellular matrix-receptor interaction, cell adhesion molecules, and complement and coagulation cascades. MiR-23b-3p was confirmed to target ANXA2 by dual-luciferase reporter assay. CONCLUSIONS: Upregulated expression of ANXA2 may promote the malignant biological behavior of THCA by affecting the involving pathways or being targeted by miR-23b-3p.

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