Background: Non-receptor protein tyrosine phosphatases (PTPNs) are a set of enzymes involved in the tyrosyl phosphorylation. The present study intended to clarify the associations between the expression patterns of PTPN family members, and diagnosis as well as the prognosis of digestive tract cancers.Methods: Oncomine and Ualcan were used to analyze PTPN expressions. Data from The Cancer Genome Atlas (TCGA) were downloaded through UCSC Xena for validation and to explore the relationship of the PTPN expression with diagnosis, clinicopathological parameters and survival of digestive tract cancers. Gene ontology enrichment analysis was conducted using the DAVID database. The gene–gene interaction network was performed by GeneMANIA and the protein–protein interaction (PPI) network was built using STRING portal coupled with Cytoscape. The expression of differentially expressed PTPNs in cancer cell lines were explored using CCLE. Moreover, by histological verification, the expression of four PTPNs in digestive tract cancers were further analyzed.Results: Most PTPN family members were associated with digestive tract cancers according to Oncomine, Ualcan and TCGA data. Several PTPN members were differentially expressed in digestive tract cancers. For esophageal carcinoma (ESCA), PTPN1 and PTPN12 levels were correlated with incidence; PTPN20 was associated with poor prognosis. For stomach adenocarcinoma (STAD), PTPN2 and PTPN12 levels were correlated with incidence; PTPN3, PTPN5, PTPN7, PTPN11, PTPN13, PTPN14, PTPN18 and PTPN23 were correlated with pathological grade; PTPN20 expression was related with both TNM stage and N stage; PTPN22 was associated with T stage and pathological grade; decreased expression of PTPN5 and PTPN13 implied worse overall survival of STAD, while elevated PTPN6 expression indicated better prognosis. For colorectal cancer (CRC), PTPN2, PTPN21 and PTPN22 levels were correlated with incidence; expression of PTPN5, PTPN12, and PTPN14 was correlated with TNM stage and N stage; high PTPN5 or PTPN7 expression was associated with increased hazards of death. CCLE analyses showed that in esophagus cancer cell lines, PTPN1, PTPN4 and PTPN12 were highly expressed; in gastric cancer cell lines, PTPN2 and PTPN12 were highly expressed; in colorectal cancer cell lines, PTPN12 was highly expressed while PTPN22 was downregulated. Results of histological verification experiment showed differential expressions of PTPN22 in CRC, and PTPN12 in GC and CRC.Conclusions: Members of PTPN family were differentially expressed in digestive tract cancers. Correlations were found between PTPN genes and clinicopathological parameters of patients. Expression of PTPN12 was upregulated in both STAD and CRC, and thus could be used as a diagnostic biomarker. Differential expression of PTPN12 in GC and CRC, and PTPN22 in CRC were presented in our histological verification experiment.

Matrix metalloproteinase-9 (MMP9) has been reported to play a key role in the pathogenesis of aortic aneurysm. However, few studies have assessed serum MMP9 levels in both abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). In this study, we investigated the serum levels of MMP9 in aortic aneurysm to evaluate its predictive and diagnostic efficacy for AAA and TAA, and explored the association of MMP9 with circulating laboratory markers. A total of 296 subjects were enrolled, including 105 AAA patients, 79 TAA patients and 112 healthy controls. The levels of serum MMP9 were detected by enzyme-linked immunosorbent assay (ELISA). Compared to control group, both AAA and TAA patients had higher serum MMP9 levels in the overall comparison and subgroup analysis based on subjects aged<65 years, either male or female, hypertension, non-diabetes and non-hyperlipidemia (all P<0.05). Moreover, MMP9 levels were significantly higher in TAA group than those in AAA group in the total comparison, and this discrepancy was also found in the non-diabetes, non-hyperlipidemia and aortic diameter ≥ 5.5 cm subgroup analysis. Serum MMP9 levels were influenced by age and hypertension. There was a positive association of serum MMP9 with CRP (r = 0.33, P < 0.001) and Hcy (r = 0.199, P = 0.033). Multiple logistic analyses showed that serum MMP9 was an independent risk factor for AAA and TAA. Based on receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of MMP9 for predicting TAA was 0.83 with 70% sensitivity and 91% specificity, while the AUC of MMP9 to detect AAA was 0.69 and the sensitivity and specificity were 50% and 88%. Serum MMP9 was closely related to the existence of aortic aneurysms and could be a valuable marker for the discrimination of aortic aneurysm, especially for TAA.

Background: Aberrant expression of N6-methyladenosine (m6A) RNA modification regulators plays a critical role in a variety of human diseases. However, their implication in abdominal aortic aneurysm (AAA) remains largely unknown. Herein, we sought to explore the general expression pattern and potential functions of m6A regulators in AAA. Methods: We analyzed gene expression data of m6A regulators in human AAA and normal tissues from public GEO database. The R package and other tools such as m6A2Target database, Gene ontology (GO) functional and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses, gene set variation analysis (GSVA), Search Tool for the Retrieval of Interacting Genes (STRING), starBase, miRDB and Cytoscape software were applied for bioinformatics analysis to investigate the downstream molecular mechanisms and upstream regulatory mechanisms for distinctly expressed regulators. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to validate the expression of key m6A regulators in our collected human AAA specimens. Results: We found that METTL14 and HNRNPC were the downregulated m6A regulators, and RBM15B was the upregulated methylation transferase in human AAA. The modified genes were primarily enriched in RNA catabolic process, regulation of translation, focal adhesion, transcription coregulator activity, ribosome, RNA transport, cell cycle, et al. METTL14, HNRNPC and RBM15B levels were correlated with the immune infiltration degree of Tcm, macrophages, mast cells, Tgd and NK CD56bright cells. A total of 154 and 76 target genes of three regulators were separately involved in body metabolism and autophagy in AAA disease, and their interactive relationships and hub genes were identified. The lncRNA-miRNA-mRNA interaction regulatory networks were also constructed for METTL14, HNRNPC and RBM15B. Based on our clinical tissue and serum samples, METTL14 exhibited lower expression levels in AAA and its rupture type, and low METTL14 expression was associated with high levels of WBC and CRP (all P < 0.05). Conclusion: Our study presents an overview of the expression pattern and functional significance of m6A regulators in human AAA. Our findings will provide a valuable resource that may guide both mechanistic and therapeutic analyses about the role of key m6A regulators in AAA.

Aim: To explore the expression profiles of N6-methyladenosine (m6A) enzymes (writers, erasers and readers) and their associations with gastric cancer (GC) prognosis. Methods: Gene expression was an... Lay abstract RNA N6-methyladenosine (m6A) methylation is modulated by a series of epigenetic modulator enzymes termed ‘writers’, ‘erasers’ and ‘readers’. We aimed to explore the expression profiles...

Background: Ribosomal RNA N6-methyltransferase METTL5 was reported to catalyze m⁶A in 18S rRNA. We aimed to investigate the expression and prognostic features of METTL5 in gastric cancer (GC). Methods: In this study, 168 GC patients and their corresponding adjacent tissues were collected. Immunohistochemical staining was used to detect the expression of METTL5 protein. Univariate and multivariate Cox analysis were used to dertermine the prognostic role of METTL5 protein in GC, and a nomogram was constructed to evaluate GC patients’ prognosis based on METTL5 expression. Data from TCGA and GEO database were also used to validate the prognostic value of METTL5 in GC patients on mRNA level. We further performed GSEA enrichment analysis to explore the possible function and related pathways related to METTL5. Results: METTL5 protein in gastric cancer tissues (GCTs) was significantly decreased compared with adjacent normal tissues (ANTs) and adjacent intestinal metaplasia tissues (AIMTs) (P < 0.001, respectively). Meanwhile, METTL5 expression was negatively correlated with clinicopathologic stage. According to multivariate Cox proportional hazards model analysis, METTL5 protein expression was a good independent predictor of GC prognosis (p < 0.05). Patients with high METTL5 expression had better prognosis. The nomogram constructed based on METTL5 expression could predict the prognosis of GC patients well. GSEA analysis showed that genes of METTL5 low expression group were enriched in some oncogenic signaling pathways such as ERBB, MAPK, JAK-STAT, Wnt, and mTOR, as well as some immune pathways, including Fc-gamma R mediated phagocytosis, Fc-epsilon Ri, chemokine, T cell receptor and B cell receptor signaling pathway. While the high expression group of METTL5 was mainly related to oxidative phosphorylation, nucleotide excision repair and mismatch repair. Conclusions: METTL5 protein was decreased in GCTs compared with AIMTs and ANTs, and it may be a potential prognostic biomarker in GC.

Matrix metalloproteinase 9 (MMP9) and Toll-like receptor 4 (TLR4) play important roles in aortic pathophysiology. However, there is lacking research on serum TLR4 levels in acute aortic dissection (AAD) patients, and the performance of serum MMP9 and TLR4 for the diagnosis of AAD is still unknown. This study aimed to evaluate the serum levels of MMP9 and TLR4 in AAD patients, identify their associations with circulating C-reactive protein (CRP) and D-dimer, which are well-known classical biomarkers of AAD, and further explore the potential diagnostic role of MMP9 and TLR4 in AAD. Serum levels of MMP9 and TLR4 were measured by enzyme-linked immunosorbent assay (ELISA) in 88 AAD patients and 88 controls. The clinical test related information was collected from patients’ electronic medical records. Serum MMP9 and TLR4 levels were significantly higher in AAD patients than those in healthy controls in the general and stratified comparisons. Either serum MMP9 or TLR4 was independently associated with the risk of AAD (all p < 0.001). There was a positive significant association between serum MMP9 and TLR4 (r = 0.518, p < 0.001). Both MMP9 and TLR4 levels were statistically correlated with circulating CRP, but not D-dimer. Based on receiver-operating characteristic (ROC) analysis, the area under the curves (AUCs) of MMP9 and TLR4 alone for the diagnosis of AAD were 0.810 and 0.799 with optimal cut-off points of 379.47 ng/ml and 7.83 ng/ml, respectively. Moreover, a combination of serum MMP9 and TLR4 increased the AUC to 0.89 with a sensitivity of 60.2% and specificity of 94.3%. Serum MMP9 and TLR4 could be potential biomarkers for identifying AAD, while the combined diagnostic value was higher in safely ruling out AAD.