Identification of immune-related biomarkers for intracerebral hemorrhage diagnosis based on RNA sequencing and machine learning.

Background: Intracerebral hemorrhage (ICH) is a severe stroke subtype with high morbidity, disability, and mortality rates. Currently, no biomarkers for ICH are available for use in clinical practice. We aimed to explore the roles of RNAs in ICH pathogenesis and identify potential diagnostic biomarkers. Methods: We collected 233 individual blood samples from two independent cohorts, including 64 patients with ICH, 59 patients with ischemic stroke (IS), 60 patients with hypertension (HTN) and 50 healthy controls (CTRL) for RNA sequencing. Differentially expressed genes (DEGs) analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were performed to identify ICH-specific modules. The immune cell composition was evaluated with ImmuneCellAI. Multiple machine learning algorithms to select potential biomarkers for ICH diagnosis, and further validated by quantitative real-time polymerase chain reaction (RT-PCR). Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value of the signature for ICH. Finally, we generated M1 and M2 macrophages to investigate the expression of candidate genes. Results: In both cohorts, 519 mRNAs and 131 lncRNAs were consistently significantly differentially expressed between ICH patients and HTN controls. Gene function analysis suggested that immune system processes may be involved in ICH pathology. ImmuneCellAI analysis revealed that the abundances of 11 immune cell types were altered after ICH in both cohorts. WGCNA and GSEA identified 18 immune-related DEGs. Multiple algorithms identified an RNA panel (CKAP4, BCL6, TLR8) with high diagnostic value for discriminating ICH patients from HTN controls, CTRLs and IS patients (AUCs: 0.93, 0.95 and 0.82; sensitivities: 81.3%, 84.4% and 75%; specificities: 100%, 96% and 79.7%, respectively). Additionally, CKAP4 and TLR8 mRNA and protein levels decreased in RAW264.7 M1 macrophages and increased in RAW264.7 M2 macrophages, while BCL6 expression increased in M1 macrophages but not in M2 macrophages, which may provide potential therapeutic targets for ICH. Conclusions: This study demonstrated that the expression levels of lncRNAs and mRNAs are associated with ICH, and an RNA panel (CKAP4, BCL6, TLR8) was developed as a potential diagnostic tool for distinguishing ICH from IS and controls, which could provide useful insight into ICH diagnosis and pathogenesis.

The treatment of Tofacitinib for rosacea through the inhibition of the JAK/STAT signaling pathway.

Rosacea is a chronic inflammatory skin disease characterized by facial erythema and telangiectasia. Despite ongoing research, the pathogenesis of rosacea remains incompletely understood, and current therapies are not entirely satisfactory. The JAK/STAT signaling pathway plays an essential role in immunoregulation, inflammation, and neurovascular regulation. Inhibition of the JAK/STAT pathway appears to hold promise as a potential therapy for rosacea. This study aimed to investigate the effects of the JAK inhibitor tofacitinib on rosacea and to preliminarily explore its therapeutic mechanism. To this end, a rosacea-like mouse model was induced using LL37 and treated with a 2% tofacitinib emulsion. The results demonstrated that topical application of tofacitinib significantly ameliorated rosacea-like phenotype, reduced the infiltration of CD4+ T cells and mast cells, and suppressed dermal angiogenesis. RT-qPCR analysis revealed a reduction in mRNA expression levels of STAT1, STAT4, and STAT5a in skin lesions following topical tofacitinib treatment. Additionally, three patients diagnosed with erythematotelangiectatic rosacea (ETR) were included in the study and treated with oral tofacitinib, leading to a significant improvement in erythema and flushing symptoms. These findings collectively suggest that tofacitinib alleviates LL37-induced rosacea-like skin inflammation in mice and rosacea skin lesions by inhibiting the JAK/STAT signaling pathway.

Enhancing the therapeutic impact of sublethal radiofrequency hyperthermia in malignant solid tumor treatment.

Radiofrequency ablation (RFA) is an effective alternative to surgery for managing some malignant solid tumors. However, for medium-to-large tumors (>3 cm), tumors adjacent to large blood vessels, and certain irregular tumors, sublethal radiofrequency hyperthermia (RFH) often produces a margin of ablated tumor owing to the "heat-sink" effect. This effect typically leaves behind viable residual tumors at the margin. Several studies have reported that a sublethal RFH can significantly enhance the efficacy of chemotherapy, radiotherapy, immunotherapy, and gene therapy for malignant solid tumors. The possible mechanisms by which RFH enhances these therapies include heat-induced tissue fracturing, increased permeability of the cytoplasmic membrane, exaggerated cellular metabolism, blockade of the repair pathways of radiation-damaged tumor cells, and activation of the heat shock protein pathways. Therefore, RFA in combination with chemotherapy, radiotherapy, immunotherapy, or gene therapy may help reduce the rates of residual and recurrent tumors after RFA of malignant solid tumors.

Downregulation of miR-337-3p in hypoxia/reoxygenation neuroblastoma cells increases KCTD11 expression.

Neurodegeneration is linked to the progressive loss of neural function and is associated with several diseases. Hypoxia is a hallmark in many of these diseases, and several therapies have been developed to treat this disease, including gene expression therapies that should be tightly controlled to avoid side effects. Cells experiencing hypoxia undergo a series of physiological responses that are induced by the activation of various transcription factors. Modulation of microRNA (miRNA) expression to alter transcriptional regulation has been demonstrated to be beneficial in treating multiple diseases, and in this study, we therefore explored potential miRNA candidates that could influence hypoxia-induced nerve cell death. Our data suggest that in mouse neuroblasts Neuro-2a cells with hypoxia/reoxygenation (H/R), miR-337-3p is downregulated to increase the expression of Potassium channel tetramerization domain containing 11 (KCTD11) and subsequently promote apoptosis. Here, we demonstrate for the first time that KCTD11 plays a role in the cellular response to hypoxia, and we also provide a possible regulatory mechanism by identifying the axis of miR-337-3p/KCTD11 as a promising candidate modulator of nerve cell survival after H/R exposure.

Radiofrequency hyperthermia enhances the effect of OK-432 for Hepatocellular carcinoma by activating of TLR4-cGAS-STING pathway.

Radiofrequency ablation (RFA) has been used as an alternative to surgical management of early-stage hepatocellular carcinoma (HCC). However, when large and irregular HCCs are subjected to RFA, a safety margin is usually difficult to obtain, thus causing a sublethal radiofrequency hyperthermia (RFH) at the ablated tumor margin. This study investigated the feasibility of using RFH to enhance the effect of OK-432 on HCC, with the aim to generate a tumor-free margin during RFA of HCC. Our results showed OK-432 could activate the cGAS-STING pathway, and RFH could further enhance the activation. Meanwhile, RFH could induce a high expression of TLR4, and TLR4 might be an upstream molecular of the cGAS-STING pathway. The combined therapy of RFH with OK-432 resulted in a better tumor response, and a prolonged survival compared to the other three treatments. In conclusion, RFH in combination with OK-432 might reduce the residual and recurrent tumor after RFA of large and irregular HCCs, and serve as a new option for other solid malignancies treated by RFA.

Influential factors on urine EV DNA methylation detection and its diagnostic potential in prostate cancer.

The value of Extracellular vesicles (EVs) diagnostic markers is widely recognized. However, current research on EV DNA remains limited. This study investigates the biological properties, preprocessing factors, and diagnostic potential of EV DNA. We found that DNA positive vesicles account for 23.3% ± 6.7% of the urine total EV, with a large amount of DNA attached to the outside. EV DNA fragments are large, there is no significant effect on uEV DNA when store urine less than 6 h at 4°C. In addition, the influence of different EV extraction methods on methylation detection is also minor. More importantly, RASSF1A methylation in urine total EV DNA can distinguish between PCa and BPH, with an AUC of 0.874. Our results suggest the potential of urine EV DNA as a novel marker for PCa diagnosis. This provides a new idea for the study of urinary tumor markers.

Injectable hydrogel loaded with lysed OK-432 and doxorubicin for residual liver cancer after incomplete radiofrequency ablation.

OBJECTIVE: To investigate the efficacy of an injectable hydrogel loaded with lysed OK-432 (lyOK-432) and doxorubicin (DOX) for residual liver cancer after incomplete radiofrequency ablation (iRFA) of hepatocellular carcinoma (HCC), and explore the underlying mechanism. MATERIALS AND METHODS: The effect of OK-432 and lyOK-432 was compared in activating dendritic cells (DCs). RADA16-I (R) peptide was dissolved in a mixture of lyOK-432 (O) and DOX (D) to develop an ROD hydrogel. The characteristics of ROD hydrogel were evaluated. Tumor response and mice survival were measured after different treatments. The number of immune cells and cytokine levels were measured, and the activation of cGAS/STING/IFN-I signaling pathway in DC was evaluated both in vitro and in vivo. RESULTS: LyOK-432 was more effective than OK-432 in promoting DC maturation and activating the IFN-I pathway. ROD was an injectable hydrogel for effectively loading lyOK-432 and DOX, and presented the controlled-release property. ROD treatment achieved the highest tumor necrosis rate (p < 0.001) and the longest survival time (p < 0.001) compared with the other therapies. The ROD group also displayed the highest percentages of DCs, CD4+ T cells and CD8+ T cells (p < 0.001), the lowest level of Treg cells (p < 0.001), and the highest expression levels of IFN-γ and TNF-α (p < 0.001) compared with the other groups. The expression levels of pSTING, pIRF3, and IFN-ß in DCs were obviously higher after treatment of lyOK-432 in combination with DOX than the other therapies. The surviving mice in the ROD group showed a growth inhibition of rechallenged subcutaneous tumor. CONCLUSION: The novel ROD peptide hydrogel induced an antitumor immunity by activating the STING pathway, which was effective for treating residual liver cancer after iRFA of HCC.

A 20-year bibliometric analysis of postoperative pulmonary complications: 2003-2022.

Background: Postoperative pulmonary complications (PPCs) are known to adversely affect surgical outcomes and patient prognoses, yet no published study provides a qualitative and quantitative analysis of the latest trends and developments in the field of PPCs. Therefore, we conducted a bibliometric analysis of 20 years of publications related to PPCs. Methods: We examined publications on PPCs published between 2003 and 2022 in the Web of Science Core Collection database to assess trends in the field in four dimensions: trends in publications, major research power, keywords, and co-cited publications. Results: A total of 1881 articles were analyzed using CiteSpace and VOSviewer. Overall, the number of publications on PPCs has increased in the last two decades, with 42.72% of the publications being produced in the last five years. The United States of America had the highest number of articles, accounting for 21.91% of the total. The institution with the highest number of publications was the University of Genoa, which published 54 articles and showed a general lack of inter-institutional collaboration. The most productive author was Paolo Pelosi, with no core group of authors identified in the field of PPCs. The keyword co-occurrence analysis indicated that the focus of research has shifted over the past 20 years in terms of risk factors, type of surgery, and so on, while "enhanced recovery", "prehabilitation", "driving pressure" and "sugammadex" have received the most recent attention. In the analysis of co-cited literature, the most recent clusters that received attention were driving pressure, lung cancer patient, enhanced recovery, and neuromuscular blockade. Conclusion: This bibliometric study suggests that pulmonary protective ventilation strategies, neuromuscular blockade reversal, and pulmonary prehabilitation strategy will be the focus of attention in the coming period. More large-scale studies and strengthened institutional collaboration are necessary to generate robust evidence for guiding individualized prevention of PPCs.

Jianpi Yangzheng Xiaozheng decoction alleviates gastric cancer progression via suppressing exosomal PD-L1.

Jianpi Yangzheng Xiaozheng decoction (JPYZXZ) is an empirical traditional Chinese medicine formula that has been reported to significantly prolong the survival of patients with advanced gastric cancer (GC). However, its underlying mechanism have not been fully elucidated. The present work aims to explore the possible mechanism of JPYZXZ on regulating GC progression. We firstly confirmed the inhibitory effect of JPYZXZ in GC MKN74 cells and 615-strain mice, which was possibly mediated with IL-6/JAK2/STAT3 pathway dependent PD-L1 expression. Moreover, we showed that JPYZXZ diminished the expression levels of GC-derived exosomal PD-L1 in MFC murine cells and xenograft GC model, as well as stage IIA-IIIB GC patients. We further found that in different types of tumor-infiltrating immune cells, PD-L1 expression was most positively correlated with myeloid-derived suppressor cells (MDSCs) in GC in the TISIDB database. We isolated exosomes derived from supernatants of MFC cells and co-cultured with bone marrow cells derived from C57BL/6 mice, and further revealed that the expansion of MDSCs was mediated by GC-derived exosomal PD-L1. Meanwhile, our results indicated that JPYZXZ inhibited the delivery of exosomal PD-L1 from GC cells to bone marrow cells, thereby alleviating exosomal PD-L1-induced differentiation and expansion of MDSCs in the tumor microenvironment. This led to a decrease in the levels of several immunosuppressive factors, including iNOS, Arg-1, TGF-ß, IL-10, and IL-6, in 615-strain mice. Moreover, clinical data also revealed a significant positive relationship between exosomal PD-L1 and polymorphonuclear MDSCs under the JPYZXZ treatment in stage IIA-IIIB GC patients. In conclusion, our study confirmed that exosomal PD-L1 could be a key factor in controlling MDSCs differentiation in GC. JPYZXZ alleviated GC progression via suppressing exosomal PD-L1 mediated expansion of MDSCs, thereby remodeling the immunosuppressive tumor microenvironment, which provided the experimental evidence for the clinical application of JPYZXZ in the treatment of GC via PD-L1.

Synergistic effect of OK-432 in combination with an anti-PD-1 antibody for residual tumors after radiofrequency ablation of hepatocellular carcinoma.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) often results in incomplete ablation for medium-to-large and irregular tumors. To solve this clinical problem, we proposed a new treatment strategy of OK-432 in combination with an anti-programmed cell death protein 1 (αPD-1) antibody for residual tumors after incomplete RFA (iRFA) of hepatocellular carcinoma (HCC). APPROACH AND RESULTS: The effect of OK-432 on immature dendritic cells (iDCs) was evaluated in vitro. A CCK-8 kit and ELISPOT were used to assess the killing effect of OK-432-induced CD8+ T cells in combination with an αPD-1 antibody on Hepa1-6 cells. We found that OK-432 significantly increased the maturation level of DCs, and OK-432-induced CD8+ T cells in combination with αPD-1 antibody significantly enhanced the function of CD8+ T cells. In the in vivo experiment, HCC model mice were treated with (1) pseudo iRFA + phosphate-buffered saline (PBS); (2) iRFA + PBS; (3) iRFA + OK-432; (4) iRFA + αPD-1; or (5) iRFA + OK-432 + αPD-1. We found that the combined therapy of OK-432 with αPD-1 antibody significantly increased the infiltration and function of CD8+ T cells and significantly decreased the number of FoxP3+ regulatory T cells in residual tumors after iRFA of HCC. Moreover, the smallest tumor volumes and the longest survival were observed in the triple combination treatment (iRFA+OK-432 +αPD-1 antibody) group compared with the other four groups. CONCLUSIONS: The combined therapy of OK-432 with αPD-1 antibody induced a strong antitumor immune response, which significantly inhibited the residual tumors after iRFA of HCC. This concept may provide a new treatment strategy to increase the curative efficacy of RFA for medium-to-large and irregular HCCs. AVAILABILITY OF DATA AND MATERIAL: The data of this study are available from the corresponding author on reasonable request.

Tumor-derived extracellular vesicle nucleic acids as promising diagnostic biomarkers for prostate cancer.

Liquid biopsy as a non-invasive method has a bright future in cancer diagnosis. Tumor-related extracellular vesicles (EVs) and their components (nucleic acids, proteins, and lipids) in biofluids may exert multiple functions in tumor growth, metastasis, immune escape, and angiogenesis. Among all the components, nucleic acids have attracted the most interest due to their simplicity of extraction and detection. In this review, the biological functions of EVs in prostate cancer (PCa) genesis and progression were summarized. Moreover, the diagnostic value of EV RNA markers found in clinical body fluid samples was reviewed, including their trends, challenging isolation methods, and diagnostic efficacy. Lastly, because relatively much progress has been made in PCa, studies on EV DNA markers are also discussed.

miR-92a-1-5p enriched prostate cancer extracellular vesicles regulate osteoclast function via MAPK1 and FoxO1.

BACKGROUND: We have previously reported that extracellular vesicles (EVs) derived from osteoblastic, osteoclastic and mixed prostate cancer cells promote osteoclast differentiation and inhibit osteoblast differentiation via transferring miR-92a-1-5p. In the present study, we focused on engineering miR-92a-1-5p into EVs and determining any therapeutic roles and mechanisms of the engineered EVs. METHODS: A stable prostate cancer cell line (MDA PCa 2b) overexpressing miR-92a-1-5p was constructed by lentivirus, and EVs were isolated by ultracentrifugation. The overexpression of miR-92a-1-5p in both cells and EVs was tested using qPCR. Osteoclast function was evaluated by Trap staining, mRNA expression of osteoclastic markers ctsk and trap, immunolabeling of CTSK and TRAP and microCT using either in vitro and in vivo assays. Target gene of miR-92a-1-5p was proved by a dual-luciferase reporter assay system. siRNAs were designed and used for transient expression in order to determine the role of downstream genes on osteoclast differentiation. RESULTS: Stable overexpression cells of miRNA-92a-5p was associated with EVs upregulating this microRNA, as confirmed by qPCR. Further, miR-92a-1-5p enriched EVs promote osteoclast differentiation in vitro by reducing MAPK1 and FoxO1 expression, associated with increased osteoclast function as shown by TRAP staining and mRNA expression of osteoclast functional genes. siRNA targeting MAPK1 or FoxO1 resulted in similar increase in osteoclast function. In vivo, the miR-92a-1-5p enriched EVs given via i.v. injection promote osteolysis, which was associated with reduction of MAPK1 and FoxO1 expression in bone marrow. CONCLUSION: These experiments suggest that miR-92a-1-5p enriched EVs regulate osteoclast function via reduction of MAPK1 and FoxO1.

A novel metabolism-related prognostic gene development and validation in gastric cancer.

BACKGROUND: The importance of metabolism-related alterations in the development of gastric cancer (GC) is increasingly recognized. The present study aimed to identify metabolism-related genes to facilitate prognosis of GC patients. METHODS: Gene expression datasets and clinical information of GC patients were downloaded from TCGA and GEO databases. We scored the enrichment of human metabolism-related pathways (n = 86) in GC samples by GSV, constructed prognostic risk models using LASSO algorithm and multivariate Cox regression analysis, combined with clinical information to construct a nomogram, and finally cis score algorithm to analyze the abundance of immune-related cells in different subtypes. We used Weka software to screen for prognosis-related marker genes and finally validated the expression of the selected genes in clinical cancer patient tissues. RESULTS: We identified that two GC metabolism-related signatures were strongly associated with OS and the levels of immune cell infiltration. Moreover, a survival prediction model for GC was established based on six GC metabolism-related genes. Time-dependent ROC analysis showed good stability of the risk prediction scoring model. The model was successfully validated in an independent ACRG cohort, and the expression trends of key genes were also verified in the GC tissues of patients. DLX1, LTBP2, FGFR1 and MMP2 were highly expressed in the cluster with poorer prognosis while SLC13A2 and SLCO1B3 were highly expressed in the cluster with better prognosis. CONCLUSIONS: We identified a risk predictive score model based on six metabolism-related genes related to survival, which may serve as prognostic indicators and potential therapeutic targets for GC.

CircRPPH1 promotes the stemness of gastric cancer cells by targeting miR-375/SLC7A11 axis.

This study mainly focuses on revealing the role of circRPPH1 in gastric cancer cell stemness. In vitro and in vivo experiments were performed to evaluate the effects of circRPPH1 on gastric cancer cell stemness. Luciferase reporter and RIP assays were implemented to reveal the underlying mechanisms. MiR-375 directly bound to circRPPH1 in gastric cancer cells. And circRPPH1 acted as an miR-375 sponge to positively regulate SLC7A11 expression, which has been confirmed to be the direct target of miR-375 in gastric cancer, and thus regulated ferroptosis. Moreover, circRPPH1 promoted the stemness of gastric cancer cells dependent on the miR-375/SLC7A11. This study provides a potential target for gastric cancer progression based on the circRPPH1/miR-375/SLC7A11 regulatory axis.

Electro-enhanced sulfamethoxazole degradation efficiency via carbon embedding iron growing on nickel foam cathode activating peroxymonosulfate: Mechanism and degradation pathway.

The combination of peroxymonosulfate (PMS) activation by hetero-catalysis and electrolysis (EC) attracted incremental concerns as an efficient antibiotics degradation method. In this work, carbon embedding iron (C@Fe) catalysts growing on nickel foam (NF) composite cathode (C@Fe/NF) was prepared via in-situsolvothermal growth and carbonization method and used to activate PMS toward sulfamethoxazole (SMX) degradation. The EC-[C@Fe/NF(II)]-PMS system exhibited an excellent PMS activation, with 100% SMX removal efficiency achieving within 30 min. Reactive oxygen species (ROS) generation and their roles in SMX degradation were confirmed by quenching experiments and electron paramagnetic resonance. It was found that singlet oxygen (1O2) and surface-bound radicals were responsible for SMX degradation, and 1O2 contributed the most. Furthermore, the possible SMX degradation pathways were proposed on the base of the detected degradation intermediates and density functional theory (DFT) calculation. Toxicity changes were also assessed by the Ecological Structure Activity Relationships (ESAR). This work provides a practicable strategy for synergistically enhancing PMS activation efficiency and promoting antibiotics removal.

Loading of "cocktail siRNAs" into extracellular vesicles via TAT-DRBD peptide for the treatment of castration-resistant prostate cancer.

Extracellular vesicles (EVs) are cell-derived, membranous nanoparticles that mediate intercellular communication by transferring biomolecules between cells. As natural vehicles, EVs may exhibit higher delivery efficiency, lower immunogenicity, and better compatibility than existing RNA carriers. A major limitation of their therapeutic use is the shortage of efficient, robust, and scalable methods to load siRNA of interest. Here, we report a novel strategy using polycationic membrane-penetrating peptide TAT to encapsulate siRNAs into EVs. Three TAT peptides were co-expressed with DRBD as 3TD fusion protein. The sequence-independent binding of DRBD facilitates multiplex genes targeting of mixed siRNAs. Functional assays for siRNA-mediated gene silencing of CRPC were performed after engineered EVs treatment. EVs were isolated using differential centrifugation from WPMY-1 cell culture medium. The increase of merged yellow fluorescence in the engineered EVs showed by TIRFM and the decrease in zeta potential absolute values certified the co-localization of siRNA with EVs, which indicated that siRNA had been successfully delivered into WPMY-1 EVs. qRT-PCR analysis revealed that the mRNA level of FLOH1, NKX3, and DHRS7 was dramatically decreased when cells were treated with engineered EVs loaded with siRNAs mixtures relative to the level of untreated cells. Western and flow cytometry results indicate that delivery of siRNA mixtures by engineered EVs can effectively downregulate AR expression and induce LNCaP-AI cell apoptosis. The uptake efficiency of the EVs and the significantly downregulated expression of three genes suggested the potential of TAT as efficient siRNA carriers by keeping the function of the cargoes.

Characterization of fragment sizes, copy number aberrations and 4-mer end motifs in cell-free DNA of hepatocellular carcinoma for enhanced liquid biopsy-based cancer detection.

Circulating cell-free DNA (cfDNA) fragmentomics, which encompasses the measurement of cfDNA length and short nucleotide motifs at the ends of cfDNA molecules, is an emerging field for cancer diagnosis. The utilization of cfDNA fragmentomics for the diagnosis of patients with hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) is currently limited. In this study, we utilized whole-genome sequencing data of cfDNA in samples from patients with HCC (n = 197) and HBV (n = 187) to analyze the association of fragment size selection (< 150 bp) with tumor fraction (TF), copy number variation (CNV) alterations and the change in the proportion of 4-mer end motifs in HCC and HBV samples. Our analyses identified five typical CNV markers (i.e. loss in chr1p, chr4q and chr8p, and gain in chr1q and chr8q) in cfDNA with a cumulatively positive rate of ˜ 95% in HCC samples. Size selection (< 150 bp) significantly enhanced TF and CNV signals in HCC samples. Additionally, three 4-mer end motifs (CCCA, CCTG and CCAG) were identified as preferred end motifs in HCC samples. We identified 139 end motifs significantly associated with fragment size that showed similar patterns of associations between patients with HCC and HBV, suggesting that end motifs might be inherently coupled with fragment size by a ubiquitous mechanism. Here we conclude that CNV markers, fragment size selection and end-motif pattern in cfDNA have potential for effective detection of patients with HCC.

ARF3 inhibits proliferation and promotes apoptosis in gastric cancer by regulating AKT and ERK pathway.

ADP-ribosylation factor 3 (ARF3) has confirmed participate in diverse biological processes in many cancers. However, the expression patterns and roles of ARF3 in gastric cancer (GC) remains largely unknown. In our study, by using qRT-PCR and western blot, we found that, in In GC tissues and cells, the expression of ARF3 was significantly down-regulated. Functional experiments demonstrated that ARF3 inhibited proliferation, induced cycle arrest and enhanced apoptosis of GC cells. Moreover, by performing western blot, we found that ARF3 could regulate the protein expression of key factors of AKT and ERK pathway. Using orthotopic xenograft mouse models, it is showed that ARF3 could inhibit GC tumorigenesis in vivo. To sum up, ARF3 may suppress proliferation, induced cycle arrest and promotes apoptosis of GC by modulating AKT and ERK pathway. It might act as a potential biomarker for GC prognosis.