Changes of serum P62 and Beclin 1 in patients with pulmonary embolism during treatment and their predictive value for efficacy.

OBJECTIVE: This study was designed to analyze the changes of serum P62 and Beclin 1 in patients with acute pulmonary embolism (APE) during treatment and their predictive value for efficacy. METHODS: In this retrospective study, 84 patients diagnosed as APE in Ningbo First Hospital from January 2020 to January 2022 were enrolled and assigned to a patient group, and 40 healthy individuals who underwent physical examination in Ningbo First Hospital during the same time period were assigned to a control group. Serum P62 and Beclin 1 expressions were compared between the two groups, and receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic value of serum P62 and Beclin 1. The changes of serum P62 and Beclin 1 before and after treatment were evaluated. The correlations of P62 and Beclin 1 levels with the efficacy in patients were analyzed, and corresponding ROC curves were drawn. Additionally, the expressions of serum P62 and Beclin 1 in patients with different disease degrees were determined, and their expressions in relapsed patients were compared before treatment. RESULTS: The patient group showed significantly lower level of serum P62 but higher level of Beclin 1 than the control group (P<0.05). The areas of under the curves (AUCs) of P62 and Beclin 1 in diagnosing APE were 0.888 and 0.795 respectively. After treatment, patients showed significantly increased P62 expression (P<0.05) and significantly decreased Beclin 1 expression (P<0.01). The P62 expression increased with the relief of patient's disease, with a positive correlation with the patient's disease condition, while the Beclin 1 expression decreased with the relief of patient's disease, with a negative correlation with the patient's disease condition (P<0.05). In addition, the improved group showed significantly higher serum P62 expression (P<0.05) and significantly lower serum Beclin 1 expression than the non-improved group (P<0.05), and the AUCs of P62 and Beclin 1 in predicting the efficacy in patients with APE were 0.801 and 0.675, respectively. The relapsed group showed significantly lower serum P62 expression (P<0.05) and significantly higher Beclin 1 expression than the non-relapsed group (P<0.05), and the AUCs of P62 and Beclin 1 in predicting the recurrence of APE were 0.815 and 0.769, respectively. CONCLUSION: In patients with APE, serum P62 decreased, but serum Beclin 1 increased. So, both indictors can be applied for diagnosis, efficacy prediction and recurrence prediction of APE.

Autophagy genes CCL2 and MYC are considered as potential biomarkers for pulmonary embolism.

OBJECTIVE: The pathogenesis of pulmonary embolism (PE) remains unclear. This study was designed to determine the differential genes associated with PE autophagy via the gene expression omnibus (GEO). METHODS: Microarray data sets GSE11851 and GSE13535 were downloaded from the GEO to determine the differentially expressed genes (DEGs) of PE, and the protein-protein interaction (PPI) and hub gene networks were constructed by string and Cytoscape software. Additionally, the two data sets were screened to find the autophagy-related genes with common differential expression. Then, autophagy-related hub genes (ARHGs) overlapping with autophagy-related genes and hub genes were identified. Next, the mRNA-miRNA network was constructed, and finally the expressions of hub genes were determined with GSE11851 and GSE13535. RESULTS: A total of 235 common DEGs were identified, and C-C motif chemokine ligand 2 (CCL2) and MYC proto-oncogene (MYC) were identified to be the ARHGs of PE. Additionally, a co-expression network of mRNAs and miRNAs, consisting of 94 nodes and 103 edges, was constructed by Cytoscape. PE samples showed significantly higher expressions of CCL2 and MYC than the control samples (P < 0.05). According to gene set enrichment analysis (GSEA), CCL2 was closely correlated with oxidative stress and inflammatory reaction, while MYC was closely correlated with inflammatory reaction. CONCLUSION: According to analysis, CCL2 and MYC, with high expression in PE samples, are promising potential markers of PE.

Downregulation of annexin A3 promotes ionizing radiation-induced EGFR activation and nuclear translocation and confers radioresistance in nasopharyngeal carcinoma.

Radioresistance currently poses a significant challenge to successful disease control of nasopharyngeal carcinoma (NPC). We previously uncovered that annexin A3 (ANXA3), a calcium-dependent phospholipid binding protein, is underexpressed in radioresistant NPC cells and mouse xenografts. This study aims to further unravel the mechanistic basis underlying ANXA3-mediated radioresistance in NPC. We show that either innate ANXA3 downregulation or short hairpin RNA(shRNA)-based knockdown of ANXA3 confers resistance to ionizing radiation (IR) in NPC both in vitro and in mouse xenograft models in vivo, whereas radiosensitization was observed when ANXA3 was ectopically expressed. Mechanistically, ANXA3 knockdown dramatically enhances IR-induced epidermal growth factor receptor (EGFR) phosphorylation and nuclear translocation, leading to increased post-IR phosphorylation of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) concomitant with markedly accelerated DNA DSB repair. In addition, pretreatment with cetuximab efficiently abrogated the radioresistant phenotype of ANXA3-low cells as well as the ANXA3 knockdown-induced post-IR EGFR nuclear accumulation, suggesting that EGFR is an essential mediator for ANXA3 depletion-mediated radioprotection in NPC. Collectively, this work reveals for the first time a critical role of ANXA3 in radiation survival and DNA repair mechanism of NPC and provides mechanistic evidence to support ANXA3 as a potential therapeutic target to improve radiocurability for NPC.

Excavating novel diagnostic and prognostic long non-coding RNAs (lncRNAs) for head and neck squamous cell carcinoma: an integrated bioinformatics analysis of competing endogenous RNAs (ceRNAs) and gene co-expression networks.

Long non-coding RNAs (lncRNAs) have been demonstrated to fine-tune gene regulations that govern a broad spectrum of oncogenic processes. Nonetheless, our understanding of the roles of lncRNAs and their interactions with miRNAs and mRNAs in HNSCC is still highly rudimentary. Here, we present a comprehensive bioinformatics analysis in which competing endogenous RNA (ceRNA) network construction and weighted gene co-expression network analysis (WGCNA) were combined to explore novel diagnostic and prognostic lncRNAs for HNSCC. Differentially expressed mRNAs (DEGs), miRNAs (DEMs) and lncRNAs (DELs) were identified based on the RNA sequencing data and clinical data retrieved from TCGA database. LncRNA-regulated ceRNA networks were constructed based on the interactive RNA pairs predicted by miRDB, miRcode and TargetScan. WGCNA was conducted to identify lncRNAs that were significantly correlated with patient overall survival (OS) and HNSCC tumor. RT-qPCR was employed to validate the expression of lncRNAs in HNSCC cell lines and patient sera. A ceRNA network consisting of 90 DEGs, 7 DEMs and 67 DELs associated with clinical traits was established. WGCNA and Kaplan-Meier survival analysis revealed that 5 DELs (MIR4435-2 HG, CASC9, LINC01980, STARD4-AS1 and MIR99AHG) were significantly correlated with OS of HNSCC patients, whereas DEL PART1 was most significantly correlated with the HNSCC tumor. The in silico predicted expression patterns of PART1, LINC01980 and MIR4435-2 HG were further validated in HNSCC cell lines and patient sera. Collectively, the present study provided novel insights into the lncRNA-regulated ceRNA networks in HNSCC and identified novel lncRNAs that harbor diagnostic and prognostic potentials for HNSCC.Abbreviations BP, biological process. CC, cellular component. ceRNA, competing endogenous RNA. DEG, differential expressions of mRNA. DEL, differentially expressed lncRNA. DEM, differentially expressed miRNA. ESCC, esophageal squamous cell carcinoma. FPKM, Fragments Per Kilobase Million. GO, Gene Ontology. GS, gene significance. HNSCC, head and neck squamous cell carcinoma. KEGG, Kyoto Encyclopedia of Genes and Genomes. LncRNA, long non-coding RNA. MCC, Maximal Clique Centrality. ME, module eigengenes. MF, molecular functions. MM, module membership. MRE, miRNA-binding site. MYO5A, Myosin-Va. PART1, prostate androgen-regulated transcript 1. RBM3, RNA­binding motif protein 3. TCGA, The Cancer Genome Atlas. TOM, topological overlap measure. TSCC, tongue squamous cell carcinoma. WGCNA, weighted gene co-expression network analysis.

Plasmid-encoding vasostatin inhibited the growth and metastasis of human hepatocellular carcinoma cells.

The growth and metastasis of solid tumors depends on angiogenesis. Anti-angiogenesis therapy may represent a promising therapeutic option. Vasostatin, the N-terminal domain of calreticulin, is a very potent endogenous inhibitor of angiogenesis and tumor growth. In this study, we attempted to investigate whether plasmid-encoding vasostatin complexed with cationic liposome could suppress the growth and metastasis of hepatocellular carcinoma in vivo and discover its possible mechanism of action. Apoptosis induction of pSecTag2B-vasostatin plasmid on murine endothelial cells (MS1) was examined by flow cytometric analysis in vitro. Nude mice bearing HCCLM3 tumor received pSecTag2B-vasostatin, pSecTag2B-Null, and 0.9 % NaCl solution, respectively. Tumor net weight was measured and survival time was observed. Microvessel density within tumor tissues was determined by CD31 immunohistochemistry. H&E staining of lungs and TUNEL assay of primary tumor tissues were also conducted. The results displayed that pSecTag2B-vasostatin could inhibit the growth and metastasis of hepatocellular carcinoma xenografts and prolong survival time compared with the controls in vivo. Moreover, histologic analysis revealed that pSecTag2B-vasostatin treatment increased apoptosis and inhibited angiogenesis. The present data may be of importance to the further exploration of this new anti-angiogenesis approach in the treatment of hepatocellular cancer.

[Correlation between FDG PET /CT and the expression of glutl and ki-67 antigen in esophageal cancer].

OBJECTIVE: To evaluate the correlation between standardized uptake valus (SUV) of 18F-fluorodeoxyglucose (18 F-FDG) of tumor at PET/CT examination and the expression of glucose transporter-1 (Glutl) and Ki-67 in esophageal cancer. METHODS: 56 patients with esophageal cancer were evaluated with 18 F-FDG PET/CT examination before operation. The expression of Glut1 and Ki-67 antigen in the tumor tissues was detected by immunohistochemistry after operation. RESULTS: (1) Positive rate of Glutl and Ki-67 expression in esophageal cancer tissues was 100% , respectively. There was a positive correlation between the expression of Glutl and Ki-67 and the clinical stages and differentiation of the tumor. The more the tumor and the clinical stages were advanced and the lower was the tumor differentiation, the more Glutl and Ki-67 were expressed. (2) There were abnormal radioactive high uptake regions on PET/CT imaging of esophagus in the 56 patients, which were confirmed by pathology as the primary carcinoma. The SUV was higher than 2. 5. There was a gradually increasing tendency in SUV along with the lowering of the tumor differentiation and the advance of clinical stages. (3)There was a correlation between the expression of Glutl, Ki-67 and the SUV, the more Glutl and Ki-67 were expressed, the higher the SUV of tumor 18F-FDG at PET/CT examination was in esophageal tumor tissues. CONCLUSION: There is a widespread expression of Glutl in esophageal cancer tissues, and the SUV may be used to indirectly evaluate the proliferative capacity of esophageal cancer.

[The effects of vascular endothelial growth factor on dendritic cells in esophageal tumor tissue].

AIM: To investigate the relationship between vascular endothelial growth factor (VEGF) and S100 protein positive dendritic cell (DC) in esophagelal tumor tissue. METHODS: VEGF and S100 protein in 94 patients with esophageal carcinoma were detected by HRP Labelled streptavidin biotin(LSAB) immunohistochemical method. RESULTS: Postive rate of VEGF in esophageal tumor tissues was 74.46%(70/94); and the later the clinical stage and the lower the differentiation level was the more VEGF was(r=0.864, 0.803, respectively; P<0.05); while the later the clinical stage and the lower the differentiation level was, the less number of S100(+) DCs existed (r=-0.763, -0.908, respectively; P<0.05). Furthermore, there was a reverse correlation between the expression of VEGF and S100(+) DC (r=-0.817, P<0.05). CONCLUSION: There may be a reverse relationship between the expression of VEGF and S100(+) DC in esophageal tumor tissue, VEGF could decrease the number of S100(+) DC and impair the immunological function of the body.