Screening of a Prognostic Gene Signature for Relapsed/Refractory Acute Myeloid Leukemia Based on Altered Circulating CircRNA Profiles.

Background: Relapsed/refractory acute myeloid leukemia (R/R-AML) has dismal prognosis due to chemotherapy resistance. Circular RNAs (circRNAs) have shown emerging roles in chemotherapy resistance in various cancers including hematologic malignancies. However, the potential roles of circRNAs in AML progression and drug resistance remain largely undetermined. Methods: In this study, circulating circRNAs expression profiles were analyzed among R/R-AML, de novo AML and healthy controls (HC) using a human circRNA Array. Bioinformatic analysis was carried out to explore the differentially expressed circRNAs (DE-circRNAs). GO, KEGG pathway analysis, along with circRNA-miRNA-mRNA network analysis, were conducted to identify the potential biological pathways involved in R/R-AML. Finally, the UALCAN database was used to assess the prognosis of different target DE-circRNAs-related mRNAs. Results: Forty-eight DE-circRNAs were upregulated, whereas twenty-seven DE-circRNAs were downregulated in R/R-AML samples. Up-regulated DE-circRNAs in R/R-AML samples were mainly enrichment in the biological processes and pathways of cell migration, microRNAs in cancers, Rap1 and Ras signaling pathways. Six DE-circRNAs were randomly selected to further explore their relationships with R/R-AML. GO and KEGG pathway analyses of the six candidate DE-circRNAs-related target mRNAs were mainly involved in the regulation of signal transduction and Ras signaling pathway. By overlapping our RNA-sequencing results of differentially expressed genes (DEGs) in R/R-AML samples with the candidate DE-circRNAs-predicted target mRNAs, we identified sixty-eight overlapping targeted mRNAs. Using UALCAN database analysis, we identified that AML patients with six upregulated DE-circRNA-related genes (ECE1, PI4K2A, SLC9A6, CCND3, PPP1R16B, and TRIM32) and one downregulated gene DE-circRNA-related genes (ARHGAP10) might have a poor prognosis. Conclusion: This study revealed the overall alterations of circRNAs in R/R-AML. DE-circRNAs and their related genes might be used as potential early, sensitive and stable biomarkers for AML diagnosis, R/R-AML monitoring, and even as novel treatment targets for R/R-AML.

Primary pancreatic peripheral T-cell lymphoma: A case report.

BACKGROUND: Primary pancreatic lymphoma (PPL) is an exceedingly rare tumor with limited mention in scientific literature. The clinical manifestations of PPL are often nonspecific, making it challenging to distinguish this disease from other pancreatic-related diseases. Chemotherapy remains the primary treatment for these individuals. CASE SUMMARY: In this case study, we present the clinical details of a 62-year-old woman who initially presented with vomiting, abdominal pain, and dorsal pain. On further evaluation through positron emission tomography-computed tomography, the patient was considered to have a pancreatic head mass. However, subsequent endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) revealed that the patient had pancreatic peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin, decitabine, and oxaliplatin (brentuximab vedotin and Gemox). The patient had significant improvement in radiological findings at the end of the first cycle. CONCLUSION: Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma, in which the clinical manifestations are often nonspecific. It is difficult to diagnose, and the prognosis is poor. Imaging can only be used for auxiliary diagnosis of other diseases. With the help of immunostaining, EUS-FNA could be used to aid in the diagnosis of PPL. After a clear diagnosis, chemotherapy is still the first-line treatment for such patients, and surgical resection is not recommended. A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma. However, identifying new CD30-targeted therapies for different types of lymphoma is urgently needed. In the future, further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

Correlation between red blood cell distribution width/platelet count and prognosis of newly diagnosed diffuse large B-cell lymphoma.

Background: Red blood cell distribution width/platelet count ratio (RPR) is a reliable prognostic assessment indicator for numerous diseases. However, no studies to date have examined the relationship between RPR and the prognosis of diffuse large B-cell lymphoma (DLBCL). Therefore, this study aimed to investigate the correlation between RPR and the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma. Methods: We retrospectively studied 143 patients with newly diagnosed DLBCL and used the median value as the RPR threshold. We also investigated the correlation of pretreatment RPR level with clinical characteristics and its impact on DLBCL prognosis. Results: Using the median value as the cut-off, patients with DLBCL were divided into a low RPR group (＜0.0549) and a high RPR group (≥0.0549). Patients in the high RPR group were older, had a later Ann Arbor stage, were prone to bone marrow invasion, and had a higher National Comprehensive Cancer Network International Prognostic Index score (P＜0.05). A survival analysis showed that progression-free survival (PFS) (P=0.003) and overall survival (OS) (P＜0.0001) were significantly shorter in the high versus low RPR group. A multifactorial Cox analysis showed that bone marrow invasion and elevated lactate dehydrogenase (LDH) were separate risk factors for PFS (P＜0.05), while an RPR ≥0.0549 and elevated LDH were separate risk factors for OS (P＜0.05). Conclusion: A high RPR (≥0.0549) in patients with newly diagnosed DLBCL is an independent risk factor for a poor prognosis.

Microarray analysis reveals gene and microRNA signatures in diabetic kidney disease.

The current study aimed to identify therapeutic gene and microRNA (miRNA) biomarkers for diabetic kidney disease (DKD). The public expression profile GSE30122 was used. Following data preprocessing, the limma package was used to select differentially-expressed genes (DEGs) in DKD glomeruli samples and tubuli samples and they were compared with corresponding controls. Then overlapping DEGs in glomeruli and tubuli were identified and enriched analysis was performed. In addition, protein­protein interaction (PPI) network analysis as well as sub­network analysis was conducted. miRNAs of the overlapping DEGs were investigated using WebGestal. A total of 139 upregulated and 28 downregulated overlapping DEGs were selected, which were primarily associated with pathways involved in extracellular matrix (ECM)­receptor interactions and cytokine­cytokine receptor interactions. CD44, fibronectin 1, C­C motif chemokine ligand 5 and C­X­C motif chemokine receptor 4 were four primary nodes in the PPI network. miRNA (miR)­17­5p, miR­20a and miR­106a were important and nuclear receptor subfamily 4 group A member 3 (NR4A3), protein tyrosine phosphatase, receptor type O (PTPRO) and Kruppel like factor 9 (KLF9) were all predicted as target genes of the three miRNAs in the integrated miRNA­target network. Several genes were identified in DKD, which may be involved in pathways such as ECM­receptor interaction and cytokine­cytokine receptor interaction. Three miRNAs may also be used as biomarkers for therapy of DKD, including miR­17­5p, miR­20a and miR­106a, with the predicted targets of NR4A3, PTPRO and KLF9.

Lentivirus­mediated RIG­I knockdown relieves cell proliferation inhibition, cell cycle arrest and apoptosis in ATRA­induced NB4 cells via the AKT­FOXO3A signaling pathway in vitro.

Retinoic acid inducible gene I (RIG­I) is upregulated during all­trans retinoic acid (ATRA)­induced terminal granulocytic differentiation of NB4 acute promyelocytic leukemia (APL) cells. However, the function and mechanism of RIG­I in NB4 cells remains to be fully elucidated. In the present study, lentivirus­mediated RIG­I­knockdown was used to investigate the proliferation, cell cycle and apoptotic processes of ATRA­induced NB4 cells in vitro using an MTT assay and flow cytometry, respectively. The roles of RIG­I and the AKT­FOXO3A signaling pathway were investigated using western blot analysis. The results showed that the ATRA­induced expression of RIG­I was specifically and effectively knocked down at the mRNA and protein levels by lentivirus mediated RIG­I short hairpin RNA. In addition, silencing of RIG­I reduced the ATRA­induced inhibition of NB4 cell proliferation, cell cycle arrest and apoptosis. Further investigations indicated that with ATRA­induced expression of RIG­I, levels of phosphorylated (p)AKT­Thr308 and pForkhead Box (FOX) O3A­Thr32 were decreased, the expression levels of cell cycle arrest protein p27 and the apoptotic protein, tumor necrosis factor­related apoptosis­inducing ligand (TRAIL), directly transcribed by FOXO3A were increased. By contrast, following the knockdown of ATRA­induced expression of RIG­I, the levels of pAKT­Thr308 and pFOXO3A­Thr32 were increased, and the protein expression levels of p27 and TRAIL were decreased. Taken together, these results showed that the knockdown of RIG­I reduced the inhibition of cell proliferation, cell cycle arrest and apoptosis in the ATRA­induced NB4 cells via the AKT­FOXO3A signaling pathway.