👤 Huili Jiang

The objective of this study was to examine the association between type 2 diabetes mellitus (T2DM) and genes identified in previous genome-wide association studies (GWASs) in rural Han Chinese adults. This prospective study included 1,832 adults aged ≥18 years in Deqing without diabetes at baseline. The subjects were followed up for 8.7 years on average. We selected 45 susceptible tag single-nucleotide polymorphisms (SNPs) for T2DM that have been identified in GWASs and genotyped. A Cox model was constructed to calculate the adjusted hazard ratios (aHRs) for the association between SNPs and incident T2DM. The incidence rate of T2DM was 12.0 per 1,000 person-years. After adjustment for covariates and a Bonferroni correction, rs17584499 of protein tyrosine phosphatase, receptor-type D (PTPRD), rs11257655 and rs10906115 of cell division cycle 123 gene (CDC123), and rs12970134 of melanocortin-4 receptor (MC4R) were significantly associated with incident T2DM. The aHRs for incident T2DM were 1.75 (95% confidence interval [CI]: 1.28-2.40) and 1.61 (95% CI: 1.27-2.04) in association with an increasing number of T alleles in rs17584499 and rs11257655 under an additive genetic model, and the aHR was 1.72 (95% CI: 1.33-2.22) with an increasing number of A alleles in rs10906115. The aHRs under the dominant model were 1.82 (95% CI: 1.25-2.66) for TT + CT versus CC of rs17584499 and 2.04 (95% CI: 1.47-2.86) for AA + AG versus GG of rs10966115. The aHRs under the recessive model were 2.99 (95% CI: 1.30-6.89) for TT versus CT + CC of rs17584499, 1.92 (95% CI: 1.39-2.70) for TT versus CT + CC of rs11257655, and 2.54 (95% CI:1.22-5.29) for AA versus AG + GG of rs12970134. In addition, an increased incidence of T2DM was significantly associated with the TA haplotype of rs11257655 and rs10906115 (aHR = 1.81, 95% CI: 1.12-2.92), while a decreased incidence was associated with the CG haplotype (aHR = 0.49, 95% CI: 0.35-0.68) and the CT haplotype of rs1111875 and rs5015480 (aHR = 0.61, 95% CI: 0.37-0.98). Variants of the PTPRD, CDC123, and MC4R genes were associated with the T2DM incidence in a rural Han Chinese population. Show less

This study aims to characterize the expression of ANGPTL4 in ovarian granulosa cells (GCs) and its association with polycystic ovary syndrome (PCOS). This study included 104 PCOS patients and 112 women in control group undergoing The RT-qPCR results showed that ANGPTL4 expression in the control group was significantly lower than that in the PCOS group ( Our study revealed higher ANGPTL4 expression in ovarian GCs with PCOS. Its association with glucose and lipid metabolism showed that ANGPTL4 might play an important role in PCOS metabolism and pathogenesis. Show less

Taxane-based reagents, such as Taxol, Taxotere, and Abraxane, are popular anti-cancer drugs that can differ in their clinical efficacy. This difference is generally attributed to their active pharmaceutical ingredients. Here, we report a serendipitous discovery that Taxol induces metabolic dysregulation and unfolded protein response. Surprisingly, these effects of Taxol are entirely dependent on its excipient, Cremophor EL (CrEL). We show that CrEL promotes aerobic glycolysis and in turn results in drastic upregulation of Show less

Several studies have indicated metabolic function disruption effects of bisphenol analogues through peroxisome proliferator-activated receptor (PPAR) alpha and gamma pathways. In the present study, we found for the first time that PPARβ/δ might be a novel cellular target of bisphenol analogues. By using the fluorescence competitive binding assay, we found seven bisphenol analogues could bind to PPARβ/δ directly, among which tetrabromobisphenol A (TBBPA, 18.38-fold) and tetrachlorobisphenol A (TCBPA, 12.06-fold) exhibited stronger binding affinity than bisphenol A (BPA). In PPARβ/δ-mediated luciferase reporter gene assay, the seven bisphenol analogues showed transcriptional activity toward PPARβ/δ. Bisphenol AF (BPAF), bisphenol F (BPF) and bisphenol B (BPB) even showed higher transcriptional activity than BPA, while TBBPA and TCBPA showed comparable activity with BPA. Moreover, in human liver HL-7702 cells, the bisphenol analogues promoted the expression of two PPARβ/δ target genes PDK4 and ANGPTL4. Molecular docking simulation indicated the binding potency of bisphenol analogues to PPARβ/δ might depend on halogenation and hydrophobicity and the transcriptional activity might depend on their binding affinity and hydrogen bond interactions. Overall, the PPARβ/δ pathway may provide a new mechanism for the metabolic function disruption of bisphenol analogues, and TBBPA and TCBPA might exert higher metabolic disruption effects than BPA via PPARβ/δ pathway. Show less

Diabetic cardiomyopathy (DbCM) is characterized by initial impairment of left ventricular relaxation followed by contractile dysfunction. Despite intensive research, the exact mechanism remains so far unsolved. We constructed weighted gene co-expression network analysis (WGCNA) to screen gene modules that were closely related with DbCM based on the GSE5606 dataset, which contained expression data of the cardiac left ventricle in a rodent model of streptozotocin (STZ)-induced DbCM. Then, the most related hub gene, angiopoietin-like 4 (ANGPTL4), was selected for functional WGCNA analysis revealed the yellow and green modules were most correlated with DbCM, and identified ANGPTL4 as one of the most significantly upregulated hub genes ( We found Show less

Atherosclerosis, as a chronic inflammatory disease within the arterial wall, is a leading cause of morbidity and mortality worldwide due to its role in myocardial infarction, stroke and peripheral artery disease. Additional evidence is emerging that the angiopoietin-like (ANGPTL) family of proteins participate in the pathology of this disease process via endothelial dysfunction, inflammation, dyslipidemia, calcification, foam cell formation and platelet activation. This review summarizes current knowledge on the ANGPTL family of proteins in atherosclerosis related pathological processes. Moreover, the potential value of ANGPTL family proteins as predictive biomarkers in atherosclerosis is discussed. Given the attractive role of ANGPTL3, ANGPTL4, ANGPTL8 in atherosclerotic dyslipidemia via regulation of lipoprotein lipase (LPL), antisense oligonucleotide or/and monoclonal antibody-based inactivation of these proteins represent potential atherosclerotic therapies. Show less

Joint capsule fibrosis caused by excessive inflammation leading to post-traumatic joint contracture (PTJC). Fibroblasts trigger inflammation under the challenge of various proinflammatory cytokines. Macrophage migration inhibitory factor (MIF) is a prominent proinflammatory cytokine involved in inflammation- and fibrosis-associated pathophysiology, we investigated the role of MIF in PTJC. Using rat PTJC model and fibroblast inflammation model, we detected MIF expression in posterior joint capsule. Primary joint capsule fibroblasts (JFs) were used to investigate the effects of MIF on cell proliferation, migration and proinflammatory cytokines production. The mechanism of JF-mediated events was evaluated by qRT-PCR, western blot and immunoprecipitation. We screened the mRNA expression profile to identify gene candidates that mediate the effect of MIF on JFs. MIF increased in posterior joint capsule following PTJC and co-localized with fibroblasts. Injection of MIF inhibitor significantly suppressed joint capsule inflammation and fibrosis. MIF/CD74 axis elicited JF inflammation and may provide new therapeutic targets for joint capsule fibrosis in PTJC. Show less

The occurrence and development of hepatocellular carcinoma (HCC) remain unclear. This study aimed to investigate potential diagnostic or prognostic markers for early HCC by applying bioinformatic analysis. The gene expression profiles of early HCC and normal tissues from a TCGA dataset were used to identify differentially expressed genes (DEGs) and then analysed by weighted gene coexpression network analysis. The integrated genes were selected to construct the protein-protein interaction (PPI) network and determine the hub genes. The prognostic impact of the hub genes was then analysed. A total of 508 integrated genes were selected from the 615 DEGs and 8956 genes in the turquoise module. A PPI network was constructed, and the top 20 hub genes, including apolipoprotein A-IV (APOA4), fibrinogen gamma chain (FGG), vitamin K-dependent protein Z (PROZ), secreted phosphoprotein 24 (SPP2) and fetuin-B (FETUB), were identified. Only PROZ was significantly associated with the prognosis of early HCC. In this study, we demonstrated that the expression of PROZ was decreased in early HCC compared with normal liver controls, and low PROZ expression might result in poor overall survival of early HCC. Show less

To screen for obstructive sleep apnea (OSA) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-labeled quantitative proteomics assay was used to identify differentially expressed proteins (DEPs) during chronic intermittent hypoxia (CIH). The iTRAQ technique was applied to compare DEPs in the serum of a CIH rat model and control group. Biological analysis of DEPs was performed using Gene Ontology and Kyoto Encyclopedia to explore related biological functions and signaling pathways. Enzyme-linked immunosorbent assay (ELISA) was performed to validate their expression in sera from patients with OSA and CIH rats. Twenty-three DEPs (fold change ≥1.2 or ≤0.833, p<0.05) were identified, and two DEPs (unique peptides>3 and higher coverage) were further verified by ELISA in the CIH rat model and OSA subject: apolipoprotein A-IV (APOA4, p<0.05) and Tubulin alpha-1A chain (TUBA1A, p<0.05). Both groups showed significant differences in the expression levels of DEPs between the CIH and control groups and the severe OSA and non-OSA groups. APOA4 was found to be upregulated and TUBA1A downregulated in both the sera from OSA patients and CIH rats, on comparing proteomics results with clinical results. There were two pathways that involved three DEPs, the mitogen-activated protein kinase (MAPK) signaling pathway (p<0.05) and cytokine-cytokine receptor interaction (p<0.05). APOA4 and TUBA1A may be potential novel biomarkers for CIH and OSA, and may play an important role in the development of OSA complications. Show less

Recent evidence supports an association between lipid metabolism dysfunction and the pathology of schizophrenia which has led to the search for peripheral blood-based biomarkers. The purpose of this study was to investigate the proteins involved in lipid metabolism (especially apolipoprotein) and to explore their potential as biomarkers for schizophrenia. Using multiple reaction monitoring mass spectrometry (MRM-MS), we quantified 22 proteins in serum samples of 109 healthy controls (HCs) and 111 patients with schizophrenia (SCZ), who were divided into discovery and validation sets. We found serum apolipoprotein A4 (ApoA4) to be significantly decreased in SCZ patients compared to HCs (p=1.61E-05). Moreover, the serum ApoA4 level served as an effective diagnostic tool, achieving area under the receiver operating characteristic curves (AUROC) of 0.840 in the discovery set and 0.791 in the validation set. Additionally, apolipoprotein F (ApoF), angiotensinogen (AGT), and alpha1-antichymotrypsin (ACT) levels were significantly higher in patients with schizophrenia than in healthy controls. These proteins combined with ApoA4, provided higher diagnostic accuracy for schizophrenia in the discovery set (AUROC=0.901) and in the validation set (AUROC=0.879). Our results suggest that the serum level of ApoA4 is a novel potential biomarker for schizophrenia. The proteins identified in this study expand the pool of biomarker candidates for schizophrenia and may be linked to the underlying mechanism of the disease. Show less

Global knockout of the BK channel has been proven to affect bone formation; however, whether it directly affects osteoblast differentiation and the mechanism are elusive. In the current study, we further investigated the role of BK channels in bone development and explored whether BK channels impacted the differentiation and proliferation of osteoblasts via the canonical Wnt signaling pathway. Our findings demonstrated that knockout of Kcnma1 disrupted the osteogenesis of osteoblasts and inhibited the stabilization of β-catenin. Western blot analysis showed that the protein levels of Axin1 and USP7 increased when Kcnma1 was deficient. Together, this study confirmed that BK ablation decreased bone mass via the Wnt/β-catenin signaling pathway. Our findings also showed that USP7 might have the ability to stabilize the activity of Axin1, which would increase the degradation of β-catenin in osteoblasts. Show less

Irinotecan/5-fluorouracil (5-FU; FOLFIRI) or oxaliplatin/5-FU (FOLFOX), combined with bevacizumab or cetuximab, are approved, first-line treatments for metastatic colorectal cancer (mCRC). We aimed at identifying germline variants associated with survival in patients with mCRC treated with these regimens in Cancer and Leukemia Group B/SWOG 80405. Patients with mCRC receiving either FOLFOX or FOLFIRI were randomized to either cetuximab or bevacizumab. DNA from peripheral blood was genotyped for approximately 700,000 SNPs. The association between SNPs and overall survival (OS) was tested in 613 patients of genetically estimated European ancestry using Cox proportional hazards models. The four most significant SNPs associated with OS were three haplotypic SNPs between microsomal glutathione S-transferase 1 ( This is the first large genome-wide association study ever conducted in patients with mCRC treated with first-line standard treatment in a randomized phase III trial. A common SNP in Show less

Metabolic reprogramming is a major feature of many tumors including non-small cell lung cancer (NSCLC). Branched-chain α-keto acid dehydrogenase kinase (BCKDK) plays an important role in diabetes, obesity, and other diseases. However, the function of BCKDK in NSCLC is unclear. This study aimed to explore the function of BCKDK in NSCLC. Metabolites in the serum of patients with NSCLC and the supernatant of NSCLC cell cultures were detected using nuclear magnetic resonance (NMR) spectroscopy. Colony formation, cell proliferation, and cell apoptosis were assessed to investigate the function of BCKDK in the progression of NSCLC. Glucose uptake, lactate production, cellular oxygen consumption rate, extracellular acidification rate, and reactive oxygen species (ROS) were measured to examine the function of BCKDK in glucose metabolism. The expression of BCKDK was measured using reverse transcriptase-polymerase chain reaction, western blot, and immunohistochemical assay. Compared with healthy controls and postoperative NSCLC patients, increased branched-chain amino acid (BCAA) and decreased citrate were identified in the serum of preoperative NSCLC patients. Upregulation of BCKDK affected the metabolism of BCAAs and citrate in NSCLC cells. Knockout of BCKDK decreased the proliferation and exacerbated apoptosis of NSCLC cells ex vivo, while increased oxidative phosphorylation and, ROS levels, and inhibited glycolysis. BCKDK may influence glycolysis and oxidative phosphorylation by regulating the degradation of BCAA and citrate, thereby affecting the progression of NSCLC. Show less

Here, we investigate the role of SmERF73, a group VII ETHYLENE RESPONSE FACTOR stress response transcription factor, in the regulation of post-modification of the skeleton precursors of diterpene tanshinones in Salvia miltiorrhiza. Most genes found to be involved in tanshinone biosynthesis are located on chromosome 6, and five of these genes comprise a large gene cluster in S. miltiorrhiza. We found that SmERF73 overexpression in S. miltiorrhiza coordinately up-regulated the transcription of seven tanshinone biosynthetic genes, four of which were located in the tanshinone gene cluster, consequently increasing tanshinone accumulation, while SmERF73 silencing reduced corresponding gene transcription and tanshinone accumulation. SmERF73 recognizes GCC-box promoter elements of four tanshinone-associated genes (DXR1, CPS1, KSL1 and CYP76AH3) and activates their expression. Moreover, SmERF73 and its targets were up-regulated by stress elicitors; SmERF73 appears to be at least partly mediated by the jasmonic acid (JA) signaling pathway via interaction with SmJAZ3. SmERF73 coordinately regulates tanshinone biosynthetic gene expression, suggesting a potential link between tanshinone production and plant stress responses. Show less

Aspirin can prevent or inhibit inflammation-related cancers, such as colorectal cancer and hepatocellular carcinoma (HCC). However, the effectiveness of chemotherapy may be compromised by activating oncogenic pathways in cancer cells. Elucidation of such chemoresistance mechanisms is crucial to developing novel strategies to maximize the anti-cancer effects of aspirin. Here, we report that aspirin markedly induces CREB/ATF1 phosphorylation in HCC cells, which compromises aspirin's anti-HCC effect. Inhibition of AMP-activated protein kinase (AMPK) abrogates the induction of CREB/ATF1 phosphorylation by aspirin. Mechanistically, activation of AMPK by aspirin results in decreased expression of the urea cycle enzyme carbamoyl-phosphate synthase 1 (CPS1) in HCC cells and xenografts. Treatment with aspirin or CPS1 knockdown stimulates soluble adenylyl cyclase expression, thereby increasing cyclic AMP (cAMP) synthesis and stimulating PKA-CREB/ATF1 signaling. Importantly, abrogation of aspirin-induced CREB/ATF1 phosphorylation could sensitize HCC to aspirin. The bis-benzylisoquinoline alkaloid berbamine suppresses the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A), leading to protein phosphatase 2A-mediated downregulation of CREB/ATF1 phosphorylation. The combination of berbamine and aspirin significantly inhibits HCC in vitro and in vivo. These data demonstrate that the regulation of cAMP-PKA-CREB/ATF1 signaling represents a noncanonical function of CPS1. Targeting the PKA-CREB/ATF1 axis may be a strategy to improve the therapeutic effects of aspirin on HCC. Show less

G-quadruplex (G4) DNA is a type of quadruple helix structure formed by a continuous guanine-rich DNA sequence. Emerging evidence in recent years authenticated that G4 DNA structures exist both in cell-free and cellular systems, and function in different diseases, especially in various cancers, aging, neurological diseases, and have been considered novel promising targets for drug design. In this review, we summarize the detection method and the structure of G4, highlighting some non-canonical G4 DNA structures, such as G4 with a bulge, a vacancy, or a hairpin. Subsequently, the functions of G4 DNA in physiological processes are discussed, especially their regulation of DNA replication, transcription of disease-related genes (c-MYC, BCL-2, KRAS, c-KIT et al.), telomere maintenance, and epigenetic regulation. Typical G4 ligands that target promoters and telomeres for drug design are also reviewed, including ellipticine derivatives, quinoxaline analogs, telomestatin analogs, berberine derivatives, and CX-5461, which is currently in advanced phase I/II clinical trials for patients with hematologic cancer and BRCA1/2-deficient tumors. Furthermore, since the long-term stable existence of G4 DNA structures could result in genomic instability, we summarized the G4 unfolding mechanisms emerged recently by multiple G4-specific DNA helicases, such as Pif1, RecQ family helicases, FANCJ, and DHX36. This review aims to present a general overview of the field of G-quadruplex DNA that has progressed in recent years and provides potential strategies for drug design and disease treatment. Show less

Lung cancer is one of the most prevalent cancers in both men and women worldwide. The nucleic acid G4 structures have been implicated in the transcriptional programmes of cancer-related genes in some cancers such as lung cancer. However, the role of the dominant G4 resolvase DHX36 in the progression of lung cancer remains unknown. In this study, by bioinformatic analysis of public datasets (TCGA and GEO), we find DHX36 is an independent prognosis indicator in non-small-cell lung carcinoma (NSCLC) with subtype dependence. The stable lentiviral knockdown of the DHX36 results in accelerated migration and aggregation of the S-phase subpopulation in lung cancer cells. The reduction of DHX36 level de-sensitises the proliferation response of lung cancer cells to chemotherapeutic drugs such as paclitaxel with cell dependence. The knockdown of this helicase leads to promoted tumour growth, demonstrated by a 3D fluorescence spheroid lung cancer model, and the stimulation of cell colony formation as shown by single-cell cultivation. High throughput proteomic array indicates that DHX36 functions in lung cancer cells through regulating multiple signalling pathways including activation of protein activity, protein autophosphorylation, Fc-receptor signalling pathway, response to peptide hormone and stress-activated protein kinase signalling cascade. A causal transcriptomic analysis suggests that DHX36 is significantly associated with mRNA surveillance, RNA degradation, DNA replication and Myc targets. Therefore, we unveil that DHX36 presents clinical significance and plays a role in tumour suppression in lung cancer, and propose a potentially new concept for an anti-cancer therapy based on helicase-specific targeting. Show less

Post-transcriptional regulation of mRNA translation and stability is primarily achieved by RNA-binding proteins, which are of increasing importance for heart function. Furthermore, G-quadruplex (G4) and G4 resolvase activity are involved in a variety of biological processes. However, the role of G4 resolvase activity in heart function remains unknown. The present study aims to investigate the role of RNA helicase associated with adenylate- and uridylate-rich element (RHAU), an RNA-binding protein with G4 resolvase activity in postnatal heart function through deletion of Rhau in the cardiomyocytes of postnatal mice. RHAU-deficient mice displayed progressive pathological remodeling leading to heart failure and mortality and impaired neonatal heart regeneration. RHAU ablation reduced the protein levels but enhanced mRNA levels of Yap1 and Hexim1 that are important regulators for heart development and postnatal heart function. Furthermore, RHAU was found to associate with both the 5' and 3' UTRs of these genes to destabilize mRNA and enhance translation. Thus, we have demonstrated the important functions of RHAU in the dual regulation of mRNA translation and stability, which is vital for heart physiology. Show less

To explore the long-term influence of methamphetamine abuse on metabolomics character, with gas chromatography-mass spectrometry (GS-MS) technology, and the potential regulatory network using the bioinformatics method. Forty withdrawal methamphetamine abusers (WMA) were recruited from Shanghai Gaojing Forced Isolation Detoxification Institute. Forty healthy controls (HC) were recruited from society. GS-MS technology was used to detect metabolic products in serum. A bioinformatics method was used to build a regulatory network. Q-PCR was used to detect the candidate gene expressions, and ELISA was used to detect the regulatory enzyme expressions. Four pathways were significantly changed in the MA compared to the HC: (1) the arginine synthesis pathway, (2) alanine, aspartic acid and glutamate metabolic pathway, (3) cysteine and methionine metabolic pathway, and (4) the ascorbate and aldarate pathway (enrichment analysis Methamphetamine abuse influences the metabolic process in the long term, and Show less

The complications caused by diabetes mellitus (DM) are the focus of clinical treatment. However, little is known about diabetic enteropathy (DE) and its potential underlying mechanism. Intestinal epithelial cells (IECs) and intestinal epithelial stem cells (IESCs) were harvested from BKS.Cg-Dock7 Abnormal differentiation of IECs was observed in the mice with DM. The expression of Rspo3 was upregulated in the IECs from the mice with DM. This phenomenon was associated with Rspo3 overexpression. Additionally, Rspo3 is a major determinant of Lgr5+ stem cell identity in the diabetic state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays revealed that microRNA (miR)-380-5p directly targeted Rspo3. Moreover, miR-380-5p upregulation was observed to attenuate the abnormal differentiation of IECs by regulating Rspo3 expression. Together, our results provide definitive evidence of the essential role of Rspo3 in the differentiation of IECs in DM. Show less

FBXO31 is the substrate receptor of one of many CUL1-RING ubiquitin ligase (CRL1) complexes. Here, we show that low FBXO31 mRNA levels are associated with high pre-operative prostate-specific antigen (PSA) levels and Gleason grade in human prostate cancer. Mechanistically, the ubiquitin ligase CRL1 Show less

FGF8-FGFR1 signalling is involved in multiple biological processes, while impairment of this signalling is one of the main reasons for isolated hypogonadotropic hypogonadism (IHH). Recently, several negative modulators of FGF8-FGFR1 signalling were also found to be involved in IHH, including A total of 196 patients with IHH were enrolled in this study. Whole-exome sequencing was performed to identify variants, which was verified by PCR and Sanger sequencing. Four heterozygous Our study greatly enriched the genotypic and phenotypic spectra of Show less

Lung cancer is the leading cause of death worldwide. Especially, non-small cell lung cancer (NSCLC) has higher mortality rate than the other cancers. The high mortality rate is partially due to lack of efficient biomarkers for detection, diagnosis and prognosis. To find high efficient biomarkers for clinical diagnosis of NSCLC patients, we used gene differential expression and gene ontology (GO) to define a set of 26 tumor suppressor (TS) genes. The 26 TS genes were down-expressed in tumor samples in cohorts GSE18842, GSE40419, and GSE21933 and at stages 2 and 3 in GSE19804, and 15 TS genes were significantly down-expressed in tumor samples of stage 1. We used S-scores and N-scores defined in correlation networks to evaluate positive and negative influences of these 26 TS genes on expression of other functional genes in the four independent cohorts and found that SASH1, STARD13, CBFA2T3 and RECK were strong TS genes that have strong accordant/discordant effects and network effects globally impacting the other genes in expression and hence can be used as specific biomarkers for diagnosis of NSCLC cancer. Weak TS genes EXT1, PTCH1, KLK10 and APC that are associated with a few genes in function or work in a special pathway were not detected to be differentially expressed and had very small S-scores and N-scores in all collected datasets and can be used as sensitive biomarkers for diagnosis of early cancer. Our findings are well consistent with functions of these TS genes. GSEA analysis found that these 26 TS genes as a gene set had high enrichment scores at stages 1, 2, 3 and all stages. Show less

The exostosin (EXT) protein family is involved in diverse human diseases. However, the expression and prognostic value of EXT genes in human lung squamous cell carcinoma (LUSC) is not well understood. In this study, we analyzed the association between expression of EXT1 and EXT2 genes and survival in patients with LUSC using bioinformatics resources such as Oncomine and The Cancer Genome Atlas (TCGA) databases, the Gene Expression Profiling Interactive Analysis (GEPIA) server and Kaplan-Meier plotter. Furthermore, regulatory microRNAs (miRNAs) were predicted for EXT1 and used to establish a potential miRNA-messenger RNA (mRNA) regulation network for LUSC using the ENCORI platform. We observed that EXT1 and EXT2 expression levels were higher in LUSC than those in normal tissues. However, only EXT1 expression was significantly associated with poor overall survival (OS) in LUSC patients. Functional annotation enrichment analysis showed that genes co-expressed with the EXT1 gene were enriched in biological processes such as cell adhesion and migration, and KEGG pathways such as extracellular matrix receptor interactions, complement and coagulation cascades, and cell death. Furthermore, three miRNAs, hsa-mir-190a-5p, hsa-mir-195-5p, and hsa-mir-490-3p, were identified to be potentially involved in the regulation of EXT1. In summary, we identified EXT1 expression as a novel potential prognostic marker for human LUSC and the regulatory miRNAs that could possibly contribute to the prognosis of the disease. Show less

Fatty acid desaturase 1 (FADS1) has been reported to be a potential biomarker in various cancers. However, no study has explored the relationship between FADS1 expression and bladder cancer. Our study aimed to investigate the role of FADS1 in bladder cancer prognosis via The Cancer Genome Atlas (TCGA). RNA-Seq expression of 414 tumor tissues and 19 paired normal tissues, as well as corresponding clinical data, were downloaded from the TCGA database. Two cancer cases were excluded due to a lack of clinical information. The association between FADS1 and the clinicopathological features of bladder cancer was analyzed. This study was conducted in October 2019 in China. The high expression of FADS1 in bladder cancer was significantly related to histological grade (OR = 0.155 for low vs. high), clinical stage (OR=2.074 for III or IV vs. I or II), T classification (OR=2.326 for T3 or T4 vs. T1 or T2), lymphatic metastasis (OR=1.923 for N1 or N2 or N3 vs. N0) and distant metastasis (OR=4.883 for yes vs. no) (all p-values <0.05). Bladder cancer with high FADS1 levels was related to a worse prognosis than bladder cancer with low FADS1 levels (p= 1.626*10-5), according to median expression value 3.622. FADS1 was an independent factor of overall survival in bladder cancer, with a hazard ratio of 1.048 (95%CI: 1.020-1.077, p = 0.001). Increased FADS1 expression in bladder cancer is associated with advanced clinicopathological features and may be a potential biomarker for poor prognosis. Show less

The overall survival of metastatic colon adenocarcinoma (COAD) remains poor, so it is important to explore the mechanisms of metastasis and invasion. This study aimed to identify invasion-related genetic markers for prognosis prediction in patients with COAD. Three molecular subtypes (C1, C2, and C3) were obtained based on 97 metastasis-related genes in 365 COAD samples from The Cancer Genome Atlas (TCGA). A total of 983 differentially expressed genes (DEGs) were identified among the different subtypes by using the limma package. A 6-gene signature (ITLN1, HOXD9, TSPAN11, GPRC5B, TIMP1, and CXCL13) was constructed via Lasso-Cox analysis. The signature showed strong robustness and could be used in the training, testing, and external validation (GSE17537) cohorts with stable predictive efficiency. Compared with other published signatures, our model showed better performance in predicting outcomes. Pan-cancer expression analysis results showed that ITLN1, TSPAN11, CXCL13, and GPRC5B were downregulated and TIMP1 was upregulated in most tumor samples, including COAD, which was consistent with the results of the TCGA and GEO cohorts. Western blot analysis and immunohistochemistry were performed to validate protein expression. Tumor immune infiltration analysis results showed that TSPAN11, GPRC5B, TIMP1, and CXCL13 protein levels were significantly positively correlated with CD4+ T cells, macrophages, neutrophils, and dendritic cells. Further, the TIMP1 and CXCL13 proteins were significantly related to the tumor immune infiltration of CD8+ T cells. We recommend using our signature as a molecular prognostic classifier to assess the prognostic risk of patients with COAD. Show less

The relationship between cancer and autoimmunity is complex. However, the incidence of solid tumors such as melanoma has increased significantly among patients with previous or newly diagnosed systemic autoimmune disease (AID). At the same time, immune checkpoint blockade (ICB) therapy of cancer induces Show less

Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m Show less

The pathogenesis of ankylosing spondylitis (AS) remains unclear but appears to be associated with heredity and the environment. The mouth links the external environment to the gut and lungs. In the present study, compared to that observed in healthy controls (HCs), AS saliva was depleted of Bacilli such as Streptococcus, enriched with Clostridia such as Show less