Background. Over the past ten years, the incidence rate of papillary thyroid carcinoma (PTC) worldwide has been increasing rapidly year by year, with the incidence rate increasing 6% annually. PTC has become the malignant tumor with the highest growth rate in the world that fourteen PTC-related mutant genes have been identified. Whether the BRAFV600E mutation related to more aggressive clinicopathologic features and worse outcome in PTC remains variable and controversial. We aim to investigate the risk factors that may predict the BRAFV600E mutation potential of these lesions and new prevention strategies in PTC patients. Methods. A total of 9,908 papillary thyroid carcinoma patients with average 74.6% BRAFV600E mutations were analyzed (RevMan 5.3 software) in this study. The PubMed, Embase, and ISI Web of Science databases were systematically searched for works published through December 15, 2021. Results. The following variables were associated with an increased risk of BRAFV600E mutation in PTC patients: age ≥ 45 years ( OR = 1.39 , 95 % CI = 1.21 – 1.60 , p < 0.00001 ), male gender ( OR = 1.13 , 95 % CI = 0.99 – 1.28 , p = 0.06 ), multifocality ( OR = 1.22 , 95 % CI = 1.07 – 1.40 , p = 0.004 ), lymph node metastasis ( OR = 1.33 , 95 % CI = 0.79 – 2.23 , p = 0.28 ), extrathyroidal extension + ( OR = 1.61 , 95 % CI = 1.06 – 2.44 , p = 0.03 ), vascular invasion + ( OR = 2.04 , 95 % CI = 1.32 – 3.15 , p = 0.001 ), and tumor node metastasis stage ( OR = 1.61 , 95 % CI = 1.38 – 1.88 , p < 0.00001 ). In addition, tumor size (>1 cm) ( OR = 0.51 , 95 % CI = 0.32 – 0.81 , p = 0.005 ) and distant metastasis ( OR = 0.69 , 95 % CI = 0.22 – 2.21 , p = 0.54 ) had no association or risk with BRAFV600E mutation in PTC patients. Conclusion. Our systematic review identified the following significant risk factors of BRAFV600E mutation in PTC patients: age (≥45 years), gender (male), multifocality, lymph node metastasis, vascular invasion, extrathyroidal extension, and advanced tumor node metastasis stage (stages III and IV). Tumor size (>1 cm) and distant metastasis do not appear to be correlated with BRAFV600E mutation in PTC patients.

Focal segmental glomerulosclerosis (FSGS) is a chronic glomerular disease associated with podocyte injury which is named after the pathologic features of the kidney. The aim of this study is to decode the key changes in gene expression and regulatory network involved in the formation of FSGS. Integrated network analysis included Gene Expression Omnibus (GEO) datasets to identify differentially expressed genes (DEGs) between FSGS patients and healthy donors. Bioinformatics analysis was used to identify the roles of the DEGs and included the development of protein-protein interaction (PPI) networks, Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and the key modules were assured. The expression levels of DEGs were validated using the additional dataset. Eventually, transcription factors and ceRNA networks were established to illuminate the regulatory relationships in the formation of FSGS. 1130 DEGs including 475 upregulated genes and 655 downregulated genes with functional enrichment analysis were determined. Further analysis uncovered that the validated hub genes were defined as candidate genes, including Complement C3a Receptor 1 (C3AR1), C-C Motif Chemokine Receptor 1(CCR1), C-X3-C Motif Chemokine Ligand 1 (CX3CL1), Melatonin Receptor 1A (MTNR1A), and Purinergic Receptor P2Y13 (P2RY13). More importantly, we identified transcription factors and mRNA-miRNA-lncRNA regulatory networks associated with the candidate genes. The candidate genes and regulatory networks discovered in this study can help to comprehend the molecular mechanism of FSGS and supply potential targets for the diagnosis and therapy of FSGS.

Background. The treatment of platinum-resistant recurrent ovarian cancer (PROC) is a clinical challenge and a hot topic. Tumor microenvironment (TME) as a key factor promoting ovarian cancer progression. Macrophage is a component of TME, and it has been reported that macrophage phenotype is related to the development of PROC. However, the mechanism underlying macrophage polarization and whether macrophage phenotype can be used as a prognostic indicator of PROC remains unclear. Methods. We used ESTIMATE to calculate the number of immune and stromal components in high-grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas database. The differential expression genes (DEGs) were analyzed via protein–protein interaction network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) analysis to reveal major pathways of DEGs. CD80 was selected for survival analysis. IL-6 was selected for gene set enrichment analysis (GSEA). A subsequent cohort study was performed to confirm the correlation of IL-6 expression with macrophage phenotype in peripheral blood and to explore the clinical utility of macrophage phenotype for the prognosis of PROC patients. Results. A total of 993 intersecting genes were identified as candidates for further survival analysis. Further analysis revealed that CD80 expression was positively correlated with the survival of HGSOC patients. The results of GO and KEGG analysis suggested that macrophage polarization could be regulated via chemokine pathway and cytokine–cytokine receptor interaction. GSEA showed that the genes were mainly enriched in IL-6-STAT-3. Correlation analysis for the proportion of tumor infiltration macrophages revealed that M2 was correlated with IL-6. The results of a cohort study demonstrated that the regulation of macrophage phenotype by IL-6 is bidirectional. The high M1% was a protective factor for progression-free survival. Conclusion. Thus, the macrophage phenotype is a prognostic indicator in PROC patients, possibly via a hyperactive IL-6-related pathway, providing an additional clue for the therapeutic intervention of PROC.

Whether TERT promoter mutation is related to more aggressive clinicopathologic features and worse outcomes in papillary thyroid carcinoma patients (PTCs) is still variable and controversial. Our intention was to investigate the risk or prognostic factors that may additionally predict the TERT promoter mutation doable of these lesions and new prevention techniques in PTCs. A total of 2,539 PTC patients with 11.50% TERT mutation have been analyzed using Revman 5.3 software in this study. The PubMed and Embase databases were systematically searched for works published until November 9, 2021. The following variables had been associated with an extended chance of TERT promoter mutation in PTC patients: age < 45 years ( MD = 10.93 , 95 % CI = 7.25 – 14.61 ); gender = male ( pooled   OR = 1.63 , 95 % CI = 1.17 – 2.28 ); tumor   size > 1   cm ( MD = 0.56 , 95 % CI = 0.34 – 0.77 ); lymph node metastasis ( pooled   OR = 1.29 , 95 % CI = 0.93 – 1.79 ); vascular invasion ( pooled   OR = 1.78 , 95 % CI = 0.83 – 3.84 ); extrathyroidal extension ( pooled   OR = 2.00 , 95 % CI = 1.32 – 3.02 ); distant metastasis ( pooled   OR = 1.46 , 95 % CI = 1.04 – 2.04 ); advanced TNM stage ( pooled   OR = 3.19 , 95 % CI = 2.28 – 4.45 ). In addition, multifocality ( pooled   OR = 0.67 , 95 % CI = 0.14 – 3.24 ) had no affiliation with TERT promoter mutation in PTC patients. Our finding showed that age < 45 years, male, tumor   size > 1   cm , lymph node metastasis, vascular invasion, and superior/advanced TNM stage were dangerous elements for TERT promoter mutation of worse effect in PTCs while that multifocality was once negatively correlated. TERT promoter mutation is drastically associated with recurrence and PTC-related mortality.

Background. Histone deacetylase 3 (HDAC3) plays an important role in the development and progression of a variety of cancers, but its regulatory mechanism in acute myeloid leukemia (LAML) is not entirely understood. Methods. We analyzed the expression of HDAC3 in normal and cancerous tissues using Oncomine, UALCAN, and GEO databases. Changes of the HDAC3 gene were analyzed by cBioPortal. The genes coexpressed with HDAC3 were analyzed by WebGestalt, and the predicted signaling pathways in KEGG were discussed. Results. We discovered that the expression of HDAC3 was elevated in some types of acute myeloid leukemia. The HDAC3 gene has a strong positive correlation with SLC25A5, NDUFA2, Cox4I1, and EIF3K, which regulate cell growth and development. HDAC3 transcription is higher in patients with FLT3 mutation than in healthy people. HDAC3 can be directly involved in regulating the thyroid hormone signaling pathway. MEF2D is directly involved in the cGMP-PKG signaling pathway, and the HDAC3 gene has a strong synergistic relationship with MEF2D. HDAC3 is indirectly involved in the cGMP-PKG signaling pathway, thereby indirectly regulating the expression levels of p53 and p21 genes in patients with LAML. Genomics of Drug Sensitivity in Cancer (GDSC) database analysis revealed that the application of the HDAC3 inhibitor can inhibit the proliferation of leukemia cells. Conclusions. Therefore, our data suggest that HDAC3 may be a possible therapeutic target for acute myeloid leukemia.