In the hematology department, the availability of biomarkers for early detection of infection is difficult to obtain. The present study aimed to compare the diagnostic values of neutrophil CD64 Index, procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) and to determine whether the combined analysis of these biomarkers offer stronger predictive power in the diagnosis for the infection of febrile patients.Neutrophil CD64 Index, PCT, IL-6 and CRP levels were determined in 356 febrile patients in the hematology ward from May 2013 to May 2015. Sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, receiver operating characteristic (ROC) areas under the curve (AUC), and logistic regression analysis were determined to evaluate the diagnostic values of these biomarkers.The levels of the four biomarkers were higher in the infection patients (p<0.001), and the PCT and IL-6 were higher in the patients with positive microbial blood culture (p<0.01). The neutrophil CD64 Index, PCT, IL-6, CRP had AUCs of 0.95, 0.83, 0.75 and 0.73, respectively. The best cut-off value of the neutrophil CD64 Index to detect infections was 5.06, with high specificity (87.5%) and sensitivity (88.4%). Furthermore, neutrophil CD64 Index, PCT and IL-6 offered the best combination of diagnosis with sensitivity of 93.9% and an AUC of 0.95. In addition, the neutrophil CD64 Index may have a special value to assist the physician to diagnose infection in the neutropenic patients with fever.The neutrophil CD64 Index is useful for early identification of infections in febrile patients in the hematology department. The combined analysis of the CD64 Index, PCT and IL-6 could further improve its sensitivity.
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.
KEGG annotation of DEGs in the developing seeds of N. caudatum. KEGG annotations of DEGs among three contrast groups were performed with KASS). (XLSX 133 kb)
Gastric cancer serves as the fifth leading cause of malignancies, whose main cause of death is distant metastasis. Methyltransferase-like 3 (METTL3), a major component of N6-methyladenosine (m6A) methyltransferase complex, has been suggested to function as an oncogene in several cancers. However, its clinical value and biological mechanism in gastric cancer remain unknown. Therefore, we attempted to investigate the expression profiles, prognostic value and possible downstream signal pathways of METTL3 in gastric cancer in this study.
Methods
By analyzing data from the cancer genome atlas (TCGA), we depicted METTL3 expression profile and its possible downstream signal pathways in gastric cancer. Then, we further explored METTL3 expression and its prognostic values in 196 gastric cancers in our hospital. We established stable knockdown or overexpression of METTL3 gastric cancer SGC7901 cell lines to conduct in vitro and in vivo experiments.
Results
METTL3 was significantly elevated in tumor tissues relative to normal gastric mucosa at both mRNA and protein levels. Moreover, the results from Kaplan-Meier survival curves analysis and multivariate Cox regression analysis demonstrated that METTL3 serves as an independent prognostic factor for gastric cancer patients. Furthermore, METTL3 can promote cell proliferation, colony formation, and cell migration and invasion. Additionally, the results of gene set enrichment analysis (GSEA) indicated that the potential downstream pathways of METTL3 were involved in cell cycle controlling. The top four pathways were as follows: the DNA repair pathway, the mitotic spindle pathway, the G2M checkpoint pathway and the E2F targets pathway.
Conclusions
METTL3 was upregulated in gastric cancer and served as a promising prognostic biomarker for patients suffered this deadly disease. Moreover, METTL3 might play an oncogenic role in gastric cancer by the promotion of proliferation and invasion. The possible downstream pathways of METTL3 may be related to cell cycle controlling.
Ubiquitin-specific protease 22 (USP22) expresses highly in lung adenocarcinoma (LUAD), which are associated with poor overall survival (OS).Microarray processing was performed to determine gene expression profiling, in which it was found that knocking down USP22 resulted in abnormal expression of a large number of genes.Differentially expressed genes (DEGs)-based protein-protein interaction (PPI) network was organized into 9 functional modules.These functional modules participated significantly in protein modification-related biological process and were involved in cancer-related pathways.The network was constructed to describe the global regulation of USP22-TF/pivot-module-pathway.It suggested that knocking down USP22 may up-regulate the expression of UBC to promote the pathways of cell cycle and ubiquitin-mediated proteolysis in the development of LUAD.More than that, knocking down USP22 can up-regulate STAT1 to activate JAK1-STAT1caspase pathway, and promote apoptosis of tumor cell.Receiver operating characteristic (ROC) curve analysis suggested that E2F3, H2AFX, TFAP2A, PITX1, IRF7, and FOXM1 may be the potential diagnosis biomarkers for LUAD.On the other hand, BRCA1, FOXM1 and TFAP2A may be prognostic biomarkers of LUAD.In conclusion, we constructed a global regulation network to show that USP22 may promote the development of LUAD through ubiquitination and immunosuppression.
Background: Lymphocytes were reported to play a significant part in host anticancer immune responses and influence tumour prognosis.Few studies have focused on the prognostic values of aspartate aminotransferase (AST) to lymphocyte ratio (ALRI), aspartate aminotransferase to platelet count ratio index (APRI) and systemic immune-inflammation index (SII) in hepatocellular carcinoma (HCC) treated with palliative treatments.Methods: Five hundred and ninety-eight HCC patients treated with palliative therapies were retrospectively analysed.We randomly assigned patients into the training cohort (429 patients) and the validation cohort I (169 patients).Receiver operating characteristic (ROC) curves were used to identify the best cut-off values for the ALRI, APRI and SII in the training cohort and the values were further validated in the validation cohort I. Correlations between ALRI and other clinicopathological factors were also analysed.A prognostic nomogram including ALRI was established.We validated the prognostic value of the ALRI, SII and APRI with two independent cohorts, the validation cohort II of 82 HCC patients treated with TACE and the validation cohort III of 150 HCC patients treated with curative resection.In the training cohort and all the validation cohorts, univariate analyses by the method of Kaplan-Meier and multivariate analysis by Cox proportional hazards regression model were carried out to identify the independent prognostic factors. Results:The threshold values of ALRI, APRI and SII were 86.3, 1.37 and 376.4 respectively identified by ROC curve analysis in the training cohort.Correlation analysis showed that ALRI>86.3 was greatly associated with higher rates of Child-Pugh B&C, portal vein tumor thrombosis (PVTT) and ascites (P < 0.05).Correspondingly, ALRI level of HCC patients with Child-Pugh B&C, PVTT and ascites was evidently higher than that of HCC patients with Child-Pugh A, without PVTT and without ascites (P < 0.001).In the training cohort and the validation cohort I, II, III, the OS of patients with ALRI >86.3 was obviously shorter than patients with ALRI ≤86.3 (P <0.001).We identified ALRI as an independent prognostic factor by univariate and multivariate analyses both in training Cohort (HR=1.481,P=0.004), validation cohort I (HR=1.511,P=0.032), validation cohort II (HR=3.166,P=0.005) and validation cohort Ivyspring International Publisher III (HR=3.921,P=0.010).The SII was identified as an independent prognostic factor in training cohort (HR=1.356,P=0.020) and the validation cohort II (HR=2.678,P=0.002).The prognostic nomogram including ALRI was the best in predicting 3-month, 6-month, 1-year, 2-year survival And OS among TNM, ALRI, ALRI-TNM and nomogram.Conclusions: The ALRI was a novel independent prognostic index for the HCC patients treated with palliative treatments.
Neocinnamomum caudatum (Nees) Merr., a biodiesel tree species in the subtropical areas of South China, India and Burma, is distinctive from other species in Lauraceae family and its seed oil is rich in linoleic acid (18:2) and stearic acid (18:0). However, there is little genetic information about this species so far. In this study, a transcriptomic analysis on developing seeds of N. caudatum was conducted in an attempt to discern the molecular mechanisms involving the control of the fatty acid (FA) and triacylglycerol (TAG) biosynthesis.Transcriptome analysis revealed 239,703 unigenes with an average length of 436 bp and 137 putative biomarkers that are related to FA formation and TAG biosynthesis. The expression patterns of genes encoding β-ketoacyl-acyl carrier protein synthase I (KASI), β- ketoacyl-acyl carrier protein synthase II (KASII), stearoyl-ACP desaturase (SAD), fatty acid desaturase 2 (FAD2), fatty acid desaturase 8 (FAD8) and acyl-ACP thioesterase A/B (FATA/B) were further validated by qRT-PCR. These genes displayed a very similar expression pattern in two distinct assays. Moreover, sequence analysis of different FATBs from diverse plant species revealed that NcFATB is structurally different from its counterpart in other species in producing medium-chain saturated FAs. Concertedly, heterologous expression of NcFATB in E. coli BL21 (DE3) strain showed that this corresponding expressed protein, NcFATB, prefers long-chain saturated fatty acyl-ACP over medium-chain fatty acyl-ACP as substrate.Transcriptome analysis of developing N. caudatum seeds revealed a composite molecular map linked to the FA formation and oil biosynthesis in this biodiesel tree species. The substrate preference of NcFATB for long-chain saturated FAs is likely to contribute to its unique seed oil profile rich in stearic acid. Our findings demonstrate that in the tree species of Lauraceae family, the FATB enzymes producing long-chain FAs are structurally distinct from those producing medium-chain FAs, thereby suggesting that the FATB genes may serve as a biomarker for the classification of tree species of Lauraceae family.
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