Phase Separation of Disease-Associated SHP2 Mutants Underlies MAPK Hyperactivation.

The non-receptor protein tyrosine phosphatase (PTP) SHP2, encoded by PTPN11, plays an essential role in RAS-mitogen-activated protein kinase (MAPK) signaling during normal development. It has been perplexing as to why both enzymatically activating and inactivating mutations in PTPN11 result in human developmental disorders with overlapping clinical manifestations. Here, we uncover a common liquid-liquid phase separation (LLPS) behavior shared by these disease-associated SHP2 mutants. SHP2 LLPS is mediated by the conserved well-folded PTP domain through multivalent electrostatic interactions and regulated by an intrinsic autoinhibitory mechanism through conformational changes. SHP2 allosteric inhibitors can attenuate LLPS of SHP2 mutants, which boosts SHP2 PTP activity. Moreover, disease-associated SHP2 mutants can recruit and activate wild-type (WT) SHP2 in LLPS to promote MAPK activation. These results not only suggest that LLPS serves as a gain-of-function mechanism involved in the pathogenesis of SHP2-associated human diseases but also provide evidence that PTP may be regulated by LLPS that can be therapeutically targeted.

Phase separation underlies signaling activation of oncogenic NTRK fusions.

NTRK (neurotrophic tyrosine receptor kinase) gene fusions that encode chimeric proteins exhibiting constitutive activity of tropomyosin receptor kinases (TRK), are oncogenic drivers in multiple cancer types. However, the underlying mechanisms in oncogenesis that involve various N-terminal fusion partners of NTRK fusions remain elusive. Here, we show that NTRK fusion proteins form liquid-like condensates driven by their N-terminal fusion partners. The kinase reactions are accelerated in these condensates where the complexes for downstream signaling activation are also concentrated. Our work demonstrates that the phase separation driven by NTRK fusions is not only critical for TRK activation, but the condensates formed through phase separation serve as organizational hubs for oncogenic signaling.

In Situ Construction of Inorganics-Rich Cathode-Electrolyte Interface toward Long-Life Prussian White Cathode.

Prussian white (PW) is one of the most promising candidates as a cathode for sodium-ion batteries (SIBs) because of its high theoretical capacity, excellent rate performance, and low production cost. However, PW materials suffer severe capacity decay during long-term cycling. In this work, a robust cathode electrolyte interface (CEI) is designed on the PW cathode by employing cresyl diphenyl phosphate (CDP) and adiponitrile (ADN) as electrolyte additives. CDP and ADN possess higher highest occupied molecular orbital energy levels (HOMO) than other solvents, leading to the preferential decomposition of CDP and ADN to construct an inorganics-rich CEI layer in situ on the PW cathode. Benefiting from this CEI layer, the degradation of PW is effectively inhibited during the long cycling. The Na||PW cell achieves an excellent cycling performance with a capacity retention of 85.62% after 1400 cycles. This work presented here provides a feasible strategy for improving the cycling performance of PW by electrolyte modification.

Targeting androgen receptor phase separation to overcome antiandrogen resistance.

Patients with castration-resistant prostate cancer inevitably acquire resistance to antiandrogen therapies in part because of androgen receptor (AR) mutations or splice variants enabling restored AR signaling. Here we show that ligand-activated AR can form transcriptionally active condensates. Both structured and unstructured regions of AR contribute to the effective phase separation of AR and disordered N-terminal domain plays a predominant role. AR liquid-liquid phase separation behaviors faithfully report transcriptional activity and antiandrogen efficacy. Antiandrogens can promote phase separation and transcriptional activity of AR-resistant mutants in a ligand-independent manner. We conducted a phase-separation-based phenotypic screen and identified ET516 that specifically disrupts AR condensates, effectively suppresses AR transcriptional activity and inhibits the proliferation and tumor growth of prostate cancer cells expressing AR-resistant mutants. Our results demonstrate liquid-liquid phase separation as an emerging mechanism underlying drug resistance and show that targeting phase separation may provide a feasible approach for drug discovery.

Analysis of mild and severe neonatal enterovirus infections in a Chinese neonatal tertiary center: a retrospective case-control study.

PURPOSE: To compare the clinical characteristics, virus serotype, and outcome in cases of mild and severe enteroviral infection at a tertiary neonatal intensive care unit in China. METHODS: A retrospective analysis of cases hospitalized between June and August 2019. Samples (stool or throat swabs) were examined using reverse transcription polymerase chain reaction. Positive cases were divided into two groups: mild infection and severe infection. RESULTS: A total of 149 cases were assigned to one of two groups: mild infection (n = 104) and severe infection (n = 45). There were no significant differences between the groups in terms of sex, gestational age, birth weight, mode of delivery, and onset within 7 days. Clinical symptoms in both groups mostly resembled sepsis (fever, rash, poor feeding, and lethargy); however, there were significant variations in concomitant symptoms such as hepatitis, thrombocytopenia, encephalitis, coagulopathy, and myocarditis. Severe cases were more likely to have abnormal complete blood counts, biochemical parameters, and cerebrospinal fluid markers. The predominant serotypes implicated in neonatal enterovirus infections were echoviruses and Coxsackievirus B. Invasive ventilation, intravenous immunoglobulin, vasoactive medications, and blood product transfusions were often required, with high mortality rates among severe cases. CONCLUSION: We found significant differences between mild and severe cases of neonatal enterovirus infection with respect to complications, laboratory findings, and enterovirus serotypes. It is crucial to exercise caution when newborns exhibit symptoms of sepsis, during an enterovirus outbreak. Anemia, thrombocytopenia, abnormal liver function, and coagulation dysfunction should be monitored closely as they could indicate the presence of a severe enteroviral infection.

LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration.

Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.

M6A RNA Methylation-Mediated Dysregulation of AGAP2-AS1 Promotes Trastuzumab Resistance of Breast Cancer.

INTRODUCTION: Trastuzumab is commonly used to treat human epidermal growth factor receptor-2-positive (HER2+) breast cancer, but its efficacy is often limited by chemotherapy resistance. Recent studies have indicated that long non-coding RNAs (lncRNAs) play important roles in tumor progression and response to therapy. However, the regulatory mechanisms associating lncRNAs and trastuzumab resistance remain unknown. METHODS: Quantitative polymerase chain reaction was performed to detect the expression of related genes. Western blot and immunofluorescence assays were used to evaluate protein expression levels. A series of gain- or loss-of-function assays confirmed the function of AGAP2-AS1 in trastuzumab resistance, both in vitro and in vivo. RNA immunoprecipitation and pull-down analyses were conducted to verify the interaction between METTL3/YTHDF2 and lncRNA AGAP2-AS1. RESULTS: AGAP2-AS1 was upregulated in trastuzumab-resistant cells and SKBR-3R-generated xenografts in nude mice. Silencing AGAP2-AS1 significantly decreased trastuzumab-induced cytotoxicity both in vitro and in vivo. Furthermore, m6A methylation of AGAP2-AS1 was reduced in trastuzumab-resistant cells compared to that in parental cells. In addition, METTL3 increased m6A methylation of AGAP2-AS1, which finally induced the suppressed AGAP2-AS1 expression. Moreover, YTHDF2 was essential for METTL3-mediated m6A methylation of AGAP2-AS1. Functionally, AGAP2-AS1 regulated trastuzumab resistance by inducing autophagy and increasing ATG5 expression. CONCLUSION: we demonstrated that METTL3/YTHDF2-mediated m6A methylation increased the expression of AGAP2-AS1, which could promote trastuzumab resistance in breast cancer. AGAP2-AS1 regulates trastuzumab resistance by inducing autophagy. Therefore, AGAP2-AS1 may be a promising predictive biomarker and therapeutic target in patients with breast cancer.

Genetic polymorphisms in ESR and FSHß genes and their association with litter traits in Large White pigs.

The estrogen receptor (ESR) gene and follicle-stimulating hormone ß (FSHß) gene are responsible for litter traits. The present study aimed to verify the polymorphisms of ESR and FSHß and assess their effects on the litter traits in 201 Large White pigs. Four SNPs (g.C669T, g.A1296G, g.C1665T and g.A1755G) were found in ESR. The TT genotype at g.C1665T locus and AA genotype at g.A1755G locus could significantly increase the total litter size of the first litter of American Large White pigs (p < 0.05). Eight SNPs were found in exon 3 of FSHß. The AA genotype at g.A511G locus, AA and AG genotypes at g.A617G locus, CC and CT genotypes at g.C630T locus, CT and TT genotypes at g.C652T locus, CT and TT genotypes at g.C735T locus, AA and AG genotypes at g.A746G, AA and AG genotypes at g.A921G and CT genotype at g.C678T could significantly increase the litter size of different strains of Large White pigs (p < 0.05). Our study revealed that the genetic variations of ESR and FSHß were closely related to the litter trait of Large White pigs. Therefore, ESR and FSHß genes could be used as molecular markers for the genetic selection of Large White pigs.

PPy-Coated Mo3S4/CoMo2S4 Nanotube-like Heterostructure for High-Performance Lithium Storage.

Heterostructured materials show great potential to enhance the specific capacity, rate performance and cycling lifespan of lithium-ion batteries owing to their unique interfaces, robust architectures, and synergistic effects. Herein, a polypyrrole (PPy)-coated nanotube-like Mo3S4/CoMo2S4 heterostructure is prepared by the hydrothermal and subsequent in situ polymerization methods. The well-designed nanotube-like structure is beneficial to relieve the serious volume changes and facilitate the infiltration of electrolytes during the charge/discharge process. The Mo3S4/CoMo2S4 heterostructure could effectively enhance the electrical conductivity and Li+ transport kinetics owing to the refined energy band structure and the internal electric field at the heterostructure interface. Moreover, the conductive PPy-coated layer could inhibit the obvious volume expansion like a firm armor and further avoid the pulverization of the active material and aggregation of generated products. Benefiting from the synergistic effects of the well-designed heterostructure and PPy-coated nanotube-like architecture, the prepared Mo3S4/CoMo2S4 heterostructure delivers high reversible capacity (1251.3 mAh g-1 at 300 mA g-1), superior rate performance (340.3 mAh g-1 at 5.0 A g-1) and excellent cycling lifespan (744.1 mAh g-1 after 600 cycles at a current density of 2.0 A g-1). Such a design concept provides a promising strategy towards heterostructure materials to enhance their lithium storage performances and boost their practical applications.

A novel partially open state of SHP2 points to a "multiple gear" regulation mechanism.

The protein tyrosine phosphatase SHP2 mediates multiple signal transductions in various cellular pathways, controlled by a variety of upstream inputs. SHP2 dysregulation is causative of different types of cancers and developmental disorders, making it a promising drug target. However, how SHP2 is modulated by its different regulators remains largely unknown. Here, we use single-molecule fluorescence resonance energy transfer and molecular dynamics simulations to investigate this question. We identify a partially open, semiactive conformation of SHP2 that is intermediate between the known open and closed states. We further demonstrate a "multiple gear" regulatory mechanism, in which different activators (e.g., insulin receptor substrate-1 and CagA), oncogenic mutations (e.g., E76A), and allosteric inhibitors (e.g., SHP099) can shift the equilibrium of the three conformational states and regulate SHP2 activity to different levels. Our work reveals the essential role of the intermediate state in fine-tuning the activity of SHP2, which may provide new opportunities for drug development for relevant cancers.

Dietary amylose:amylopectin ratio influences the expression of amino acid transporters and enzyme activities for amino acid metabolism in the gastrointestinal tract of goats.

This study was designed to investigate the effects of dietary starch structure on muscle protein synthesis and gastrointestinal amino acid (AA) transport and metabolism of goats. Twenty-seven Xiangdong black female goats (average body weight = 9·00 ± 1·12 kg) were randomly assigned to three treatments, i.e., fed a T1 (normal maize 100 %, high amylose maize 0 %), T2 (normal maize 50 %, high amylose maize 50 %) and T3 (normal maize 0 %, high amylose maize 100 %) diet for 35 d. All AA in the ileal mucosa were decreased linearly as amylose:amylopectin increased in diets (P < 0·05). The plasma valine (linear, P = 0·03), leucine (linear, P = 0·04) and total AA content (linear, P = 0·03) increased linearly with the increase in the ratio of amylose in the diet. The relative mRNA levels of solute carrier family 38 member 1 (linear, P = 0·01), solute carrier family 3 member 2 (linear, P = 0·02) and solute carrier family 38 member 9 (linear, P = 0·02) in the ileum increased linearly with the increase in the ratio of amylose in the diet. With the increase in the ratio of amylose:amylopectin in the diet, the mRNA levels of acetyl-CoA dehydrogenase B (linear, P = 0·04), branched-chain amino acid transferase 1 (linear, P = 0·02) and branched-chain α-keto acid dehydrogenase complex B (linear, P = 0·01) in the ileum decreased linearly. Our results revealed that the protein abundances of phosphorylated mammalian target of rapamycin (p-mTOR) (P < 0·001), phosphorylated 4E-binding protein 1 (P < 0·001) and phosphorylated ribosomal protein S6 kinases 1 (P < 0·001) of T2 and T3 were significantly higher than that of T1. In general, a diet with a high amylose ratio could reduce the consumption of AA in the intestine, allowing more AA to enter the blood to maintain higher muscle protein synthesis through the mTOR pathway.

PhenoModifier: a genetic modifier database for elucidating the genetic basis of human phenotypic variation.

From clinical observations to large-scale sequencing studies, the phenotypic impact of genetic modifiers is evident. To better understand the full spectrum of the genetic contribution to human disease, concerted efforts are needed to construct a useful modifier resource for interpreting the information from sequencing data. Here, we present the PhenoModifier (https://www.biosino.org/PhenoModifier), a manually curated database that provides a comprehensive overview of human genetic modifiers. By manually curating over ten thousand published articles, 3078 records of modifier information were entered into the current version of PhenoModifier, related to 288 different disorders, 2126 genetic modifier variants and 843 distinct modifier genes. To help users probe further into the mechanism of their interested modifier genes, we extended the yeast genetic interaction data and yeast quantitative trait loci to the human and we also integrated GWAS data into the PhenoModifier to assist users in evaluating all possible phenotypes associated with a modifier allele. As the first comprehensive resource of human genetic modifiers, PhenoModifier provides a more complete spectrum of genetic factors contributing to human phenotypic variation. The portal has a broad scientific and clinical scope, spanning activities relevant to variant interpretation for research purposes as well as clinical decision making.

Hsa_hsa_circ_0081069 promotes the progression of colorectal cancer through sponging miR-665 and regulating E2F3 expression.

BACKGROUND: Circular RNAs (circRNAs) have been implicated in the initiation and development of various cancers. This study explored the potential contribution of hsa_hsa_circ_0081069 in the progression of colorectal cancer (CRC). METHODS: The gene expression was analyzed by qRT-PCR. Functional roles of hsa_circ_0081069 were examined by shRNA-mediated silencing using CCK-8 proliferation assay, Transwell migration and invasion assay, tube formation assay. The tumorigenesis and metastasis of CRC cells were assess in a xenograft mouse model. RESULTS: Hsa_circ_0081069 was significantly upregulated in CRC tissues and cells. Hsa_circ_0081069 knockdown suppressed the proliferation, migration and invasion in CRC cells, as well as the angiogenesis. Silencing hsa_circ_0081069 also impaired the tumorigenesis of CRC cells in a xenograft mouse model. Furthermore, miR-665 was identified as an interacting partner of hsa_circ_0081069, which was negatively regulated by hsa_circ_0081069. miR-665 targeted the mRNA of E2F3 to suppress its expression. We further demonsatred that miR-665/E2F3 axis mediated the functional role of hsa_circ_0081069 in regulating the malignant phenotype of CRC cells. CONCLUSIONS: Collectively, our study suggests that hsa_circ_0081069 could serve as a prognostic marker in progression of CRC. Targeting hsa_circ_0081069 and miR-665/E2F3 axis could serve as potential therapeutic strategies for CRC treatment.

Effects of the presence of phosphate buffer solution on removal efficiency of Pb and Zn in soil by solid phase microbial fuel cells.

Simple, effective and environment-friendly ways for remediating toxic metal pollution are necessary. In this study, the effect of different concentrations phosphate buffer solution (PBS) on removal efficiency of Pb and Zn in soil by solid phase microbial fuel cell (SMFC) was investigated. During 100 days of operation, the SMFC with 150 mM PBS generated the highest power density of 21.7 mW m-2 and the lowest internal resistance of 161 Ω. The addition of PBS can also increase soil conductivity and maintain a suitable pH for microbial activity. Furthermore, the removal rate of Pb and Zn in the SMFC with 150 mM PBS can reach 14.7% and 22.3%, respectively. The microbial community analyses demonstrated that Anditalea as an exoelectrogen in alkaline-saline conditions was significantly enriched in the SMFC with 150 mM PBS. This study provides an effective strategy for strengthening SMFC to remove toxic metals in soil.

Identification of anti-hepatic fibrosis components in Periplaneta americana based on spectrum-effect relationship and chemical component separation.

Periplaneta americana (PA) is used as a traditional medicine for hepatic diseases such as hepatic fibrosis in China. However, the relationship between the corresponding therapeutic effect and the chemical composition is still unclear. In this study, spectrum-effect relationship and chemical component separation were used to discover the potential of anti-hepatic fibrosis components of PA. The fingerprints of 10 batches of samples were established using HPLC, and the anti-hepatic fibrosis effect was determined using HSC-T6 cells. The spectrum-effect relationship between common peaks and efficacy values was established using partial least squares analysis. Partial peaks in the fingerprints were identified, including X4 (9,12-heptadecanedenoic acid glyceride), X5 (nonadecanoic acid methyl ester), X6 (glyceryl oleate), X7 (13,16,19-eicosatrienoic acid), X9 (linoleic acid), X10 (9,12,15-octadecatrienoic acid glyceride), X12 (hexadecanoic acid), X13 (oleic acid), and X14 (octadecanoic acid), and their anti-hepatic fibrosis activity was tested to verify the results of spectrum-effect relationships. The results showed that X4 , X6 , X7 , and X10 were the active ingredients of PA. This work successfully identified the partial anti-hepatic fibrosis components of PA, which can be used to explain the material basis for the PA anti-hepatic fibrosis effect.

Removal of petroleum hydrocarbon-contaminated soil using a solid-phase microbial fuel cell with a 3D corn stem carbon electrode modified with carbon nanotubes.

Solid-phase microbial fuel cell (SMFC) can accelerate the removal of organic pollutants through the electrons transfer between microorganisms and anodes in the process of generating electricity. Thus, the characteristics of the anode material will affect the performance of SMFCs. In this study, corn stem (CS) is first calcined into a 3D macroporous electrode, and then modified with carbon nanotubes (CNTs) through electrochemical deposition method. Scanning electron microscope analysis showed the CS/CNT anode could increase the contact area on the surface. Furthermore, electrochemical impedance spectroscopy and cyclic voltammetry analysis indicated the electrochemical double-layer capacitance of the CS/CNT anode increased while its internal resistance decreased significantly. These characteristics are crucial for increasing bacterial adhesion capability and electron transfer rate. The maximum output voltage of the SMFC with CS/CNT anode was 158.42 mV, and the removal rate of petroleum hydrocarbon (PH) reached 42.17%, 2.72 times that of unmodified CS. In conclusion, CNT-modified CS is conducive to improve electron transfer rate and microbial attachment, enhancing the removal efficiency of PH in soil.

A Model between Near-Surface Air Temperature Change and Dynamic Influencing Factors in the Eastern Tibetan Plateau, China.

Climate change, characterized by global warming, is profoundly affecting the global environment, politics, economy, and social security. Finding the main causes of climate change and determining their quantitative contributions are key points to making climate decisions on responses to climate change. The Tibetan Plateau (TP) is sensitive to global climate change. Taking the 100 km buffer zones of 45 meteorological stations in the eastern TP as research objects, we conducted an experimental study on temperature change and its influencing factors. Using the least squares multivariate statistical analysis method, a model between the annual and seasonal standardized temperature change and its dynamic influencing factors in the past 20 years was established. The results showed that, in the eastern TP, temperature change was affected by different factors in different periods. Vegetation cover and snow cover were the most correlated factors to temperature change. The influence of carbon dioxide, vegetation cover, and water cover was subject to seasonal changes. Urban cover and bare land cover did not pass the t-test. This research not only provides a theoretical basis for the analysis of temperature change over the TP, but also points out the direction for the analysis of temperature change causes in three polar regions.

New Catalytic Radical Process Involving 1,4-Hydrogen Atom Abstraction: Asymmetric Construction of Cyclobutanones.

While alkyl radicals have been well demonstrated to undergo both 1,5- and 1,6-hydrogen atom abstraction (HAA) reactions, 1,4-HAA is typically a challenging process both entropically and enthalpically. Consequently, chemical transformations based on 1,4-HAA have been scarcely developed. Guided by the general mechanistic principles of metalloradical catalysis (MRC), 1,4-HAA has been successfully incorporated as a key step, followed by 4-exo-tet radical substitution (RS), for the development of a new catalytic radical process that enables asymmetric 1,4-C-H alkylation of diazoketones for stereoselective construction of cyclobutanone structures. The key to success is the optimization of the Co(II)-based metalloradical catalyst through judicious modulation of D2-symmetric chiral amidoporphyrin ligand to adopt proper steric, electronic, and chiral environments that can utilize a network of noncovalent attractive interactions for effective activation of the substrate and subsequent radical intermediates. Supported by an optimal chiral ligand, the Co(II)-based metalloradical system, which operates under mild conditions, is capable of 1,4-C-H alkylation of α-aryldiazoketones with varied electronic and steric properties to construct chiral α,ß-disubstituted cyclobutanones in good to high yields with high diastereoselectivities and enantioselectivities, generating dinitrogen as the only byproduct. Combined computational and experimental studies have shed light on the mechanistic details of the new catalytic radical process, including the revelation of facile 1,4-HAA and 4-exo-tet-RS steps. The resulting enantioenriched α,ß-disubstituted cyclobutanones, as showcased with several enantiospecific transformations to other types of cyclic structures, may find useful applications in stereoselective organic synthesis.

Initiation of febuxostat for acute gout flare does not prolong the current episode: a randomized clinical trial.

OBJECTIVE: Our objective was to determine whether initiation of febuxostat during an acute gout flare prolongs the current episode. METHODS: In this randomized, placebo-controlled, single-blinded, multicentre trial, patients with acute gout flares within 72 h were randomized (1:1) to the placebo and febuxostat (40 mg/day) groups. All patients were administered diclofenac (150 mg/day) for 7 days and then open-labelled on the eighth day. Febuxostat 40 mg daily and diclofenac 75 mg daily were administered from day 8 through 28 for the remission period. The dose of diclofenac was 150 mg/day before remission in both arms, and the original protocol was maintained until remission. The primary outcome was 'days to resolution'. RESULTS: We randomized 140 patients, 70 into each arm. The mean days to resolution was 5.98 days [median 7.00, interquartile range (IQR) 2.45 days] for the placebo and 6.50 days (median 7.00, IQR 3.67 days) for the febuxostat group (P = 0.578). The rate of resolution within 7 days was 84.38% for the placebo group and 76.92% for the febuxostat group (P = 0.284). There were no statistically significant differences in joint pain, swelling, tenderness and erythema scores at days 1, 3, 5 and 7. The mean serum uric acid levels were 507.54 and 362.62 µmol/l for the placebo and febuxostat group, respectively, on day 7 (P = 0.000). The rate of recurrent gout flares was 10.00% for the placebo group and 6.56% for the febuxostat group from day 8 through 28 (P = 0.492). CONCLUSION: Initiation of febuxostat administration during an acute gout flare did not prolong the duration of acute flares. TRIAL REGISTRATION: Chinese Clinical Trial Registry, http://www.chictr.org.cn/, ChiCTR1800015962.

Bioinformatics analysis of the prognosis and biological significance of HMGB1, HMGB2, and HMGB3 in gastric cancer.

High mobility group box (HMGB) consists primarily of HMGB1, HMGB2, and HMGB3 proteins. Although abnormal HMGB expression is associated with various tumors, the relationship with gastric cancer (GC) remains unclear. In this study, HMGB1, HMGB2, and HMGB3 expression was analyzed using the Oncomine and TCGA databases. Correlations between HMGB1, HMGB2, and HMGB3 and clinicopathological factors were analyzed. cBioPortal was used to analyze HMGB1, HMGB2, and HMGB3 genetic alterations and its gene regulation network in GC tissue. HMGB1, HMGB2, and HMGB3 expression was higher in tumor tissues than in normal tissues, especially in GC. High HMGB1, HMGB2, and HMGB3 expression may predict a poor prognosis among patients with GC (hazard ratios [HR] = 1.90; 95% confidence interval [CI]: [1.30-2.78]) and human digestive system neoplasm (HR = 1.85; 95% CI [1.64-2.10]). These findings suggest that HMGB1, HMGB2, and HMGB3 may be useful prognostic indicators for patients with GC.