N6-methyladenosine-associated genetic variants in NECTIN2 and HPCAL1 are risk factors for abdominal aortic aneurysm.

Although N6-methyladenosine (m6A) modification has been implicated in the pathogenesis of abdominal aortic aneurysm (AAA), the relationship between m6A-associated single nucleotide polymorphisms (m6A-SNPs) and AAA remains unknown. This study used integrative multi-omics analysis and clinical validation approaches to systematically identify potential m6A-SNPs connected with AAA risk. We found that rs6859 and rs10198139 could modulate the expression of local genes, NECTIN2 and HPCAL1, respectively, which exhibited upregulation in AAA tissues, and their risk variants were significantly correlated with an increased susceptibility to AAA. Incorporating rs6859 and rs10198139 improved the efficiency of AAA risk prediction compared to the model considering only conventional risk factors. Additionally, these two SNPs were predicted to be located within the regulatory sequences, and rs6859 showed a substantial impact on m6A modification levels. Our findings suggest that m6A-SNPs rs6859 and rs10198139 confer an elevated risk of AAA, possibly by promoting local gene expression through an m6A-mediated manner.

ATG4B as a novel biomarker for abdominal aortic aneurysm: integrated evaluation through experimental and bioinformatics analyses.

Autophagy related gene 4B (ATG4B) plays a central role in autophagy machinery, but its clinical relevance to AAA remains unknown. In this study, 205 AAA patients and 205 age- and sex-matched controls were included to detect the serum ATG4B levels. Meanwhile, abdominal aortic specimens from 24 AAA patients and 6 human organ donors were collected to evaluate the mRNA and in situ protein expression of ATG4B. We observed significantly higher ATG4B mRNA and protein expression levels in AAA group compared to those in control group, with a positive correlation between mRNA levels and serum/in situ protein levels (serum, r = 0.518, P = 0.010; in situ, r = 0.453, P = 0.026). Serum ATG4B exhibited the diagnostic potential for AAA (AUC = 0.702, sensitivity = 75.6%) and intraluminal thrombus recognition (AUC = 0.602, sensitivity = 67.9%). Logistic regression revealed a significant association between elevated serum ATG4B and an increased risk of AAA and intraluminal thrombus formation. Deceased patients displayed higher baseline serum ATG4B levels, which could predict postoperative mortality (HR = 1.028, 95%CI = 1.007-1.049, P = 0.009, AUC = 0.612, sensitivity = 84.6%). The bioinformatics analysis suggested that ATG4B may modulate cellular autophagy and influence pathways associated with inflammation, lipid metabolism, or apoptosis, thereby contributing to the occurrence and development of AAA. The drug-gene interaction network identified 13 potential therapeutic drugs targeting ATG4B. In conclusion, ATG4B may serve as a promising biomarker for the diagnosis and prognostic assessment of AAA patients and play a key role in the pathogenesis of AAA.

A novel PCDscore based on programmed cell death-related genes can effectively predict prognosis and therapy responses of colon adenocarcinoma.

Emerging evidence suggests a correlation between oncogenesis and programmed cell death (PCD). However, comprehensive studies that incorporate all identified PCD-related genes to guide colon adenocarcinoma (COAD) prognosis and precision treatment strategies are lacking. In this study, a series of bioinformatics analyses were comprehensively conducted using data from the TCGA-COAD, GSE17538, and GSE39582 cohorts. A total of 21 PCD-associated prognostic genes were identified through univariate Cox analysis. LASSO and multivariate Cox methods were employed to establish a prognostic gene signature (ALOX12, HSPA1A, IL13, MID2, RFFL, and SLC39A8) and the corresponding scoring system, termed PCDscore, which exhibited robust predictive ability. The ssGSEA and ESTIMATE algorithms were utilized to evaluate the tumor microenvironment of COAD. The high PCDscore group demonstrated a poorer prognosis, characterized by lower CD4+ T cell infiltration and a higher stromal score. In contrast, the low PCDscore group exhibited sensitivity to common chemotherapy drugs such as Cisplatin and 5-Fluorouracil. Single-cell sequencing analysis further revealed that the high-PCDscore group displayed a lower proportion of CD4+ T cells. Colorectal cancer samples from the years 2013-2017 were employed to validate the PCDscore, while those from 2018 to 2019 served as a temporal external validation set for the PCDscore. In vitro experimental results indicated that the overexpression of SLC39A8 inhibited the proliferation and invasion of colorectal cancer cells. The study developed a novel PCDscore system based on the analysis of genes related to all identified PCD types, providing valuable insights into clinical prognosis and drug sensitivity for patients with COAD.

3D-Printed Carbon-Based Conformal Electromagnetic Interference Shielding Module for Integrated Electronics.

Electromagnetic interference shielding (EMI SE) modules are the core component of modern electronics. However, the traditional metal-based SE modules always take up indispensable three-dimensional space inside electronics, posing a major obstacle to the integration of electronics. The innovation of integrating 3D-printed conformal shielding (c-SE) modules with packaging materials onto core electronics offers infinite possibilities to satisfy ideal SE function without occupying additional space. Herein, the 3D printable carbon-based inks with various proportions of graphene and carbon nanotube nanoparticles are well-formulated by manipulating their rheological peculiarity. Accordingly, the free-constructed architectures with arbitrarily-customized structure and multifunctionality are created via 3D printing. In particular, the SE performance of 3D-printed frame is up to 61.4 dB, simultaneously accompanied with an ultralight architecture of 0.076 g cm-3 and a superhigh specific shielding of 802.4 dB cm3 g-1. Moreover, as a proof-of-concept, the 3D-printed c-SE module is in situ integrated into core electronics, successfully replacing the traditional metal-based module to afford multiple functions for electromagnetic compatibility and thermal dissipation. Thus, this scientific innovation completely makes up the blank for assembling carbon-based c-SE modules and sheds a brilliant light on developing the next generation of high-performance shielding materials with arbitrarily-customized structure for integrated electronics.

Alternative Splicing Factor Heterogeneous Nuclear Ribonucleoprotein U as a Promising Biomarker for Gastric Cancer Risk and Prognosis with Tumor-Promoting Properties.

Gastric cancer (GC) is a major global health concern with poor outcomes. Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a multifunctional protein that participates in pre-mRNA packaging, alternative splicing regulation, and chromatin remodeling. Its potential role in GC remains unclear. In this study, the expression characteristics of HNRNPU were analyzed by The Cancer Genome Atlas data, Gene Expression Omnibus data, and then further identified by real-time quantitative PCR and immunohistochemistry using tissue specimens. From superficial gastritis, atrophic gastritis, and hyperplasia to GC, the in situ expression of HNRNPU protein gradually increased, and the areas under the curve for diagnosis of GC and its precancerous lesions were 0.911 and 0.847, respectively. A nomogram integrating HNRNPU expression, lymph node metastasis, and other prognostic indicators exhibited an area under the curve of 0.785 for predicting survival risk. Knockdown of HNRNPU significantly inhibited GC cell proliferation, migration, and invasion and promoted apoptosis in vitro. In addition, RNA-sequencing analysis showed that HNRNPU could affect alternative splicing events in GC cells, with functional enrichment analysis revealing that HNRNPU may exert malignant biological function in GC progression through alternative splicing regulation. In summary, the increased expression of HNRNPU was significantly associated with the development of GC, with a good performance in diagnosing and predicting the prognostic risk of GC. Functionally, HNRNPU may play an oncogenic role in GC by regulating alternative splicing.

Clinical value of serum miR-1-3p as a potential circulating biomarker for abdominal aortic aneurysm.

BACKGROUND: Although abdominal aortic aneurysm (AAA) is associated with life-threatening complications, there are still limited reliable biomarkers for diagnostic purpose. MicroRNAs (miRNAs) have been proposed as the potential diagnostic and risk stratification markers of AAA patients, and we aim to evaluate the serum level of miR-1-3p and its diagnostic value in AAA. METHODS: This study included 200 AAA patients and 200 controls. Demographic data and clinical information were collected from the subjects' medical records. Individual image analyses of AAA morphology were determined based on computed tomography angiography (CTA). The levels of serum miRNA expression were detected by quantitative real-time PCR. Bioinformatics tools were used to identify the target genes of miR-1-3p and their potential biological functions were further enriched. RESULTS: Serum miR-1-3p levels in the AAA group were significantly lower when compared with those in the control group in overall and subgroup comparisons. It was negatively related to WBC, CRP, maximal aneurysm diameter, area, and volume in AAA patients. Circulating miR-1-3p levels could significantly discriminate between AAA patients and healthy individuals with an area under the curve (AUC) of 0.672 (95% CI = 0.619-0.724, p < 0.001), a sensitivity of 84.5% and a specificity of 45.5%. Serum miR-1-3p was associated with a reduced risk of AAA even after adjustment for possible risk factors (OR = 0.440 per unit increase, 95% CI = 0.301-0.643, p < 0.001). And low levels of serum miR-1-3p could significantly elevate the risk of AAA in both univariate and multivariate logistic regression analyses with ORs of 4.076 and 4.136, respectively (all p < 0.001). Further GO enrichment analysis revealed that miR-1-3p was mainly involved in negative regulation of apoptotic process, sprouting angiogenesis, angiogenesis, positive regulation of blood vessel endothelial cell migration, positive regulation of cell proliferation, regulation of cell shape, etc. CONCLUSIONS: MiR-1-3p can be used as a promising circulating biomarker in the development of AAA, and it may participate in multiple biological processes to play a crucial role in AAA pathogenesis.

Deep Learning-Based Stratification of Gastric Cancer Patients from Hematoxylin and Eosin-Stained Whole Slide Images by Predicting Molecular Features for Immunotherapy Response.

Determining the molecular characteristics of cancer patients is crucial for optimal immunotherapy decisions. The aim of this study was to screen immunotherapy beneficiaries by predicting key molecular features from hematoxylin and eosin-stained images based on deep learning models. An independent data set from Asian gastric cancer patients was included for external validation. In addition, a segmentation model (Horizontal-Vertical Network) was used to quantify the cellular composition of tumor stroma. The model performance was evaluated by measuring the area under the curve (AUC). The tumor extraction model achieved an AUC of 0.9386 and 0.9062 in the internal and external test sets, respectively. The stratification model could predict the immunotherapy-sensitive subtypes (AUC range, 0.8685 to 0.9461), the genetic mutations (AUC range, 0.8283 to 0.9225), and the pathway activity (AUC range, 0.7568 to 0.8612) fairly accurately. In external validation, the prediction performance of Epstein-Barr virus and programmed cell death ligand 1 expression status achieved AUCs of 0.7906 and 0.6384, respectively. The segmentation model identified a relatively high proportion of inflammatory cells and connective cells in some immunotherapy-sensitive subtypes. The deep learning-based models potentially may serve as a valuable tool to screen for the beneficiaries of immunotherapy in gastric cancer patients.

The SNP rs4591246 in pri-miR-1-3p is associated with abdominal aortic aneurysm risk by regulating cell phenotypic transformation via the miR-1-3p/TLR4 axis.

Emerging evidence reveals that single nucleotide polymorphism (SNP) within miRNAs can affect the risk of cardiovascular diseases. However, the role of miRNA SNPs in abdominal aortic aneurysm (AAA) is unclear. This study aimed to determine the association between SNPs in pri-miR-1-3p and AAA risk, as well as its underlying molecular mechanism. SNP genotyping was performed in 335 AAA patients and 335 controls using the KASP method and tissue miR-1-3p expression was measured by qRT-PCR. The biological effects of significant SNP were validated using in vitro studies. We found that the rs4591246 variant genotype was correlated with increased AAA risk and tissue miR-1-3p expression was reduced in AAA patients as compared with control subjects. An in silico approach predicted that the rs4591246 polymorphism altered the secondary structure and stability of pri-miR-1-3p, and in vitro evidence suggested that the rs4591246 polymorphism affected mature miR-1-3p expression. And luciferase assays verified TLR4 as a direct target gene of miR-1-3p. Further functional experiments demonstrated that the rs4591246 variant genotype could promote Ang II-induced cell phenotypic switching by suppressing mature miR-1-3p expression and in turn upregulating TLR4 expression, but this effect was rescued in the presence of TLR4 siRNA. In conclusion, as a promising genetic biomarker for AAA susceptibility, the SNP rs4591246 may exert its effects on AAA risk by regulating cell phenotypic transformation via the miR-1-3p/TLR4 axis.

Elevated triglyceride-glucose index predicts mortality following endovascular abdominal aortic aneurysm repair.

Background: Triglyceride-glucose (TyG) index has been increasingly studied as a simple and reliable predictor of adverse events of some cardiovascular disorders. However, its prognostic effect on postoperative outcomes in patients with abdominal aortic aneurysm (AAA) is still unknown. The current study aimed to explore the potential role of TyG index in predicting mortality of AAA patients following endovascular aneurysm repair (EVAR). Materials and methods: This retrospective cohort study analyzed the preoperative TyG index in a total of 188 AAA patients who underwent EVAR with the follow-up of 5 years. Data were analyzed with SPSS software Version 23.0. Association between the TyG index and all-cause mortality was evaluated using Cox regression models and Kaplan-Meier method. Results: Cox regression analyses showed that per 1-unit increment of TyG index was significantly associated with an increased risk of postoperative 30-day, 1-year, 3-year, and 5-year mortality, even after adjustment for potential confounders (all P<0.05). Kaplan-Meier analysis suggested that patients with high TyG index (≥8.68) had a worse overall survival (P = 0.007). Conclusion: The elevated TyG index could be a promising predictive factor of postoperative mortality in AAA patients after EVAR.

Comparative transcriptomic analysis-based identification of the regulation of foreign proteins with different stabilities expressed in Pichia pastoris.

Introduction: The industrial yeast Pichia pastoris is widely used as a cell factory to produce proteins, chemicals and advanced biofuels. We have previously constructed P. pastoris strains that overexpress protein disulfide isomerase (PDI), which is a kind of molecular chaperone that can improve the expression of an exogenous protein when they are co-expressed. Chicken cystatin (cC) is a highly thermostable cysteine protease inhibitor and a homologous protein of human cystatin C (HCC). Wild-type cC and the two mutants, I66Q and ΔW (a truncated cC lacking the á-helix 2) represent proteins with different degrees of stability. Methods: Wild-type cC, I66Q and ΔW were each overexpressed in P. pastoris without and with the coexpression of PDI and their extracellular levels were determined and compared. Transcriptomic profiling was performed to compare the changes in the main signaling pathways and cell components (other than endoplasmic reticulum quality control system represented by molecular chaperones) in P. pastoris in response to intracellular folding stress caused by the expression of exogenous proteins with different stabilities. Finally, hub genes hunting was also performed. Results and discussion: The coexpression of PDI was able to increase the extracellular levels of both wild-type cC and the two mutants, indicating that overexpression of PDI could prevent the misfolding of unstable proteins or promote the degradation of the misfolded proteins to some extent. For P. pastoris cells that expressed the I66Q or ΔW mutant, GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses of the common DEGs in these cells revealed a significant upregulation of the genes involved in protein processing, but a significant downregulation of the genes enriched in the Ribosome, TCA and Glycolysis/Gluconeogenesis pathways. Hub genes hunting indicated that the most downregulated ribosome protein, C4QXU7 in this case, might be an important target protein that could be manipulated to increase the expression of foreign proteins, especially proteins with a certain degree of instability. Conclusion: These findings should shed new light on our understanding of the regulatory mechanism in yeast cells that responds to intracellular folding stress, providing valuable information for the development of a convenient platform that could improve the efficiency of heterologous protein expression in P. pastoris.

Identifying Diagnostic and Prognostic Biomarkers and Candidate Therapeutic Drugs of Gastric Cancer Based on Transcriptomics and Single-Cell Sequencing.

Background and Objective: Gastric cancer (GC) is an important health burden and the prognosis of GC is poor. We aimed to explore new diagnostic and prognostic indicators as well as potential therapeutic targets for GC in the current study. Methods: We screened the overlapped differentially expressed genes (DEGs) from GSE54129 and TCGA STAD datasets. Protein-protein interaction network analysis recognized the hub genes among the DEGs. The roles of these genes in diagnosis, prognosis, and their relationship with immune infiltrates and drug sensitivity of GC were analyzed using R studio. Finally, the clinically significant hub genes were verified using single-cell RNA sequencing (scRNA-seq) data. Results: A total of 222 overlapping genes were screened, which were enriched in extracellular matrix-related pathways. Further, 17 hub genes were identified, and our findings demonstrated that BGN, COMP, COL5A2, and SPARC might be important diagnostic and prognostic indicators of GC, which were also correlated with immune cell infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and sensitivity of therapeutic drugs. The scRNA-seq results further confirmed that all four hub genes were highly expressed in GC. Conclusion: Based on transcriptomics and single-cell sequencing, we identified four diagnostic and prognostic biomarkers of GC, including BGN, COMP, COL5A2, and SPARC, which can help predict drug sensitivity for GC as well.

Expression and prognostic potential of ribosome 18S RNA m6A methyltransferase METTL5 in gastric cancer.

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.

Expression Pattern and Clinical Value of Key m6A RNA Modification Regulators in Abdominal Aortic Aneurysm.

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.

Associations of individual and joint expressions of ERCC6 and ERCC8 with clinicopathological parameters and prognosis of gastric cancer.

BACKGROUND: Excision repair cross-complementing group 6 and 8 (ERCC6 and ERCC8) have been implicated in ailments such as genetic diseases and cancers. However, the relationship between individual and joint expressions of ERCC6/ERCC8 and clinicopathological parameters as well as prognosis of gastric cancer (GC) still remains unclear. METHODS: In this study, protein expressions of ERCC6, ERCC8 and ERCC6-ERCC8 were detected by immunohistochemistry (IHC) in 109 paired GC and para-cancerous normal tissue samples. The mRNA expression was detected in 36 pairs of tissue samples. IHC results and RNA-seq data extracted from The Cancer Genome Atlas (TCGA) were used to explore the clinical value of ERCC6 and ERCC8 expression in GC. We further conducted protein-protein interaction analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and gene-gene interaction analysis to explore the function and regulation networks of ERCC6 and ERCC8 in GC. RESULTS: Individual and joint ERCC6/ERCC8 expression were significantly higher in adjacent normal mucosa compared with GC tissues. ERCC6 mRNA expression showed no difference in GC and paired tissues, while ERCC8 mRNA was significantly decreased in GC tissues. Protein expression of ERCC6, ERCC8, double negative ERCC6-ERCC8 and double positive ERCC6-ERCC8 and overexpressed ERCC6 mRNA were related to better clinicopathologic parameters, while overexpressed ERCC8 mRNA suggested worse parameters. Univariate survival analysis indicated that the OS was longer when ERCC6 protein expression and ERCC8 mRNA expression increased, and double negative ERCC6-ERCC8 expression was associated with a short OS. Bioinformatics analyses showed ERCC6 and ERCC8 were associated with nucleotide excision repair (NER) pathway, and six and ten gene sets were figured out to be related with ERCC6 and ERCC8, respectively. KEGG pathway showed that ERCC6/ERCC8 related gene sets were mainly involved in the regulation of PI3K/AKT/mTOR pathway. Direct physical interactions were found between ERCC6 and ERCC8. CONCLUSIONS: Individual and joint expressions of ERCC6/ERCC8 were associated with clinical features of GC. Protein expression of ERCC6, ERCC6-ERCC8, and mRNA expression of ERCC8 were related to prognosis of GC. ERCC6 and ERCC8 primarily function in the NER pathway, and may regulate GC progression through the regulation of PI3K/AKT/mTOR pathway.

Granzyme K - A novel marker to identify the presence and rupture of abdominal aortic aneurysm.

BACKGROUND: Immune inflammatory dysfunction is a hallmark of abdominal aortic aneurysm (AAA). Granzyme K (GZMK) is involved in the regulation of inflammation. However, the correlation between GZMK expression and AAA risk remains unknown. METHODS: This case-control study included 112 AAA patients and 112 controls. Serum GZMK levels were determined by enzyme-linked immunosorbent assay and immunohistochemistry was utilized to determine GZMK expression in aortic tissues. RESULTS: Compared with controls, AAA patients had higher levels of serum GZMK, and GZMK expression in AAA tissues was increased and positively associated with its serum levels (r = 0.688, P = 0.019). A positive association of serum GZMK levels with CRP or AAA diameter was confirmed, while there was a relationship between tissue GZMK expression and AAA diameter. The AUC of serum GZMK for AAA diagnosis was 0.78 with the sensitivity and specificity of 62.5% and 81.2%, whereas AUC for rupture detection was 0.76 with a sensitivity of 90.0% and specificity of 51.3%. A combination of clinically used inflammatory parameters with serum GZMK could enhance the accuracy of WBC or CRP alone in detecting AAA or rupture type. Multiple logistic analyses revealed an association of per unit increase of serum GZMK with AAA presence (OR = 1.046, P < 0.001) and its rupture risk (OR = 1.015, P = 0.048) after adjusting for confounding factors. CONCLUSIONS: Our study provides proof that elevated GZMK expression both in serum and tissues is correlated with the presence of AAA, and serum GZMK may be a useful non-invasive marker that helps to identify AAA and its rupture risk in clinical practice.

Expression profiles and prognostic roles of m6A writers, erasers and readers in gastric cancer.

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 analyzed using the UALCAN and Oncomine web resources. The prognostic roles of these genes in GC were analyzed using data from The Cancer Genome Atlas. Results: Thirteen m6A enzymes were found to be upregulated in GC tissues. The expression of m6A writers METTL3, RBM15 and WTAP was associated with pathological stage. The m6A eraser FTO was related to tumor stage and ALKBH5 expression was related to GC prognosis. The m6A reader YTHDF3 expression was associated with tumor stage. YTHDC2 was associated with survival of GC patients. Conclusion: Abnormal changes of key genes involved in m6A RNA methylation may have an important impact on GC development and prognosis.

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 of these m6A enzymes and their associations with gastric cancer (GC) development and prognosis. Gene expression was analyzed using the UALCAN and Oncomine web resources. Clinical data were downloaded from The Cancer Genome Atlas. Gene­gene networks and protein­protein interaction networks were built using the softwares STRING and GeneMANIA. Thirteen m6A enzymes were found to be upregulated in GC tissues. The expression of m6A writers METTL3, RBM15 and WTAP was associated with pathological stage. The m6A eraser FTO was related to tumor stage and ALKBH5 expression was related to GC prognosis. The m6A reader YTHDF3 expression was associated with tumor stage, and YTHDC2 was associated with survival of GC patients. In summary, these results suggest that abnormal changes of key genes involved in regulation and function of m6A RNA methylation may have an important impact on GC development and its clinical prognosis.

Single nucleotide polymorphisms of whole genes and atrophic gastritis susceptibility:a systematic review and meta-analysis.

BACKGROUND: Atrophic gastritis (AG) is one of the important precancerous lesions of gastric cancer. Single nucleotide polymorphisms (SNPs) are closely related to AG susceptibility. However, the research conclusions on the predictive potential of SNPs are inconsistent. The study aims to retrospect the association between SNPs of whole genes and AG risk by meta-analysis. MATERIALS AND METHODS: Up to April 29, 2020, a systematic literature search for the relationship of SNPs with AG susceptibility was performed utilizing PubMed, Web of Science and Chinese National Knowledge Infrastructure. The overall and stratified meta-analyses on extracted data were conducted by Stata11.2. RESULTS: 33 case-control studies were enrolled containing 9951 AG patients and 17,252 healthy controls, and 17 SNPs in 12 different genes were systematically reviewed. The results indicated that 12 genes could be categorized based on their functions, including immune response, cell proliferation and apoptosis, and DNA damage repair. For the SNPs in immune response-related genes, the C allele of TLR1 rs4833095 T/C increased AG risk to 1.21-fold and the recessive model of TLR4 rs11536878 in the TLR gene family decreased AG susceptibility to 0.48-fold. The variant alleles of IL-10 rs1800871 (OR = 1.21) and IL-8 rs4073 (OR = 1.22) in the IL gene family were positively associated with AG risk. PSCA rs2294008 enhanced AG risk in all genetic models. SNPs associated with AG susceptibility were mainly focused on immune response-related genes. CONCLUSION: These SNPs related to immune response could influence on AG risk and have potential to be AG predictive biomarkers. It is worth noting that the number of studies for each SNPs were insufficient due to the limited published researches and updated meta-analysis needs to be performed based on extensive relevant studies for more reliable results.

The expression characteristics and prognostic roles of autophagy-related genes in gastric cancer.

BACKGROUND: Autophagy is an evolutionally highly conserved process, accompanied by the dynamic changes of various molecules, which is necessary for the orderly degradation and recycling of cellular components. The aim of the study was to identify the role of autophagy-related (ATG) genes in the occurrence and development of gastric cancer (GC). METHODS: Data from Oncomine dataset was used for the differential expression analysis between cancer and normal tissues. The association of ATG genes expression with clinicopathologic indicators was evaluated by The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Moreover, using the TCGA datasets, the prognostic role of ATG genes was assessed. A nomogram was further built to assess the independent prognostic factors. RESULTS: The expression of autophagy-related genes AMBRA1, ATG4B, ATG7, ATG10, ATG12, ATG16L2, GABARAPL2, GABARAPL1, ULK4 and WIPI2 showed differences between cancer and normal tissues. After verification, ATG14 and ATG4D were significantly associated with TNM stage. ATG9A, ATG2A, and ATG4D were associated with T stage. VMP1 and ATG4A were low-expressed in patients without lymph node metastasis. No gene in autophagy pathway was associated with M stage. Further multivariate analysis suggested that ATG4D and MAP1LC3C were independent prognostic factors for GC. The C-index of nomogram was 0.676 and the 95% CI was 0.628 to 0.724. CONCLUSION: Our study provided a comprehensive illustration of ATG genes expression characteristics in GC. Abnormal expressions of the ubiquitin-like conjugated system in ATG genes plays a key role in the occurrence of GC. ATG8/LC3 sub-system may play an important role in development and clinical outcome of GC. In the future, it is necessary to further elucidate the alterations of specific ATG8/LC3 forms in order to provide insights for the discovery, diagnosis, or targeting for GC.

Potential diagnostic and prognostic value and regulatory relationship of long noncoding RNA CCAT1 and miR-130a-3p in clear cell renal cell carcinoma.

BACKGROUND: MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) could interact with each other to play a vital role in the pathogenesis of cancers. We aimed to examine the expression profile, clinical significance and regulatory relationship of miR-130a-3p and its predicted interactive lncRNA in clear cell renal cell carcinoma (ccRCC). METHODS: Bioinformatics analysis was used to predict lncRNAs binding with miR-130a-3p. qRT-PCR was employed to detect the expression levels of miR-130a-3p and the miRNA-targeted lncRNA, and their clinical values in ccRCC were clarified. The lncRNA sponge potential of miR-130a-3p was assessed through dual-luciferase reporter assay and the biological effects of them were observed. RESULTS: Colon cancer associated transcript 1 (CCAT1) directly interacted with miR-130a-3p and negatively regulated miR-130a-3p expression. CCAT1 was upregulated and miR-130a-3p was downregulated in ccRCC cell line and tissues (all P < 0.05). High CCAT1 and low miR-130a-3p expression was correlated with larger tumor size and advanced TNM stage in ccRCC patients. High CCAT1 level suggested a poor survival prognosis. There was a negative association between CCAT1 and miR-130a-3p expression (r = - 0.373, P = 0.010). MiR-130a-3p mimic and si-CCAT1 inhibited ccRCC cell proliferation and invasion, and induced apoptosis. CONCLUSIONS: CCAT1/miR-130a-3p axis may have potential to serve as a novel diagnostic and prognostic target of ccRCC patients.

XPF expression and its relationship with the risk and prognosis of colorectal cancer.

BACKGROUND: XPF (xeroderma pigmentosum complementation group F) is a key factor contributing to DNA damage excision of nucleotide excision repair pathway. The relationship between XPF expression and the risk and prognosis of colorectal cancer (CRC) is unclear. METHODS: In this experiment, a total of 824 cases of colorectal tissue were collected. XPF protein expression was detected by immunohistochemical staining. We conducted a Mann-Whitney U test in order to explore the differential expression of XPF between CRC and non-cancer controls, and the correlation between XPF expression and CRC clinicopathological parameters. Univariate and multivariate Cox regression analyses were conducted to investigate the relationship between XPF expression and CRC prognosis. The Java based software GSEA as well as STRING, David, GO, KEGG were used to explore the function and regulation network of XPF. RESULTS: The results demonstrated that the XPF expression in CRC was significantly up-regulated compared with non-tumor controls (P < 0.001) and adenoma tissue (P < 0.001). XPF protein was increased in the dynamic sequence of anal diseases to adenoma tissue to CRC. Expression of XPF was related to tumor location (P = 0.005) and tumor growth pattern (P = 0.009). The results of prognosis analysis suggested that in patients with stage T1-T2, XPF low expression may be significantly associated with better overall survival (HR = 7.978, 95% CI 1.208-52.673, P = 0.031). XPF and its interacting genes played a vital role in different processes of nucleotide excision repair pathway. XPF expression was related with Ubiquitin like protein specific protease activity. CONCLUSIONS: XPF might be a promising biomarker for CRC risk, and also showed potential as a prognostic predictor in CRC patients.