Development and validation of nomogram for predicting early recurrence after radical gastrectomy of gastric cancer.

BACKGROUND: After radical surgery, early detection of recurrence and metastasis is a crucial factor in enhancing the prognosis and survival of patients with gastric cancer (GC). Therefore, assessing the risk of recurrence in gastric cancer patients and determining the timing for postoperative recurrence is crucial. METHODS: The clinicopathological data of 521 patients with recurrent gastric cancer, who underwent radical gastrectomy at Zhejiang Cancer Hospital between January 2010 and January 2017, were retrospectively analyzed. These patients were randomly divided into two groups: a training group (n = 365) and a validation group (n = 156). In the training set, patients were further categorized into early recurrence (n = 263) and late recurrence (n = 102) groups based on a 2-year boundary. Comparative analyses of clinicopathological features and prognoses were conducted between these two groups. Subsequently, a nomogram for predicting early recurrence was developed and validated. RESULTS: In this study, the developed nomogram incorporated age, serous infiltration, lymph node metastasis, recurrence mode, and the tumour marker CA19-9. In the training cohort, the area under the curve (AUC value) was 0.739 (95% CI, 0.682-0.798), with a corresponding C-index of 0.739. This nomogram was subsequently validated in an independent validation cohort, yielding an AUC of 0.743 (95% CI, 0.652-0.833) and a C-index of 0.743. Furthermore, independent risk factors for prognosis were identified, including age, absence of postoperative chemotherapy, early recurrence, lymph node metastasis, abdominal metastasis, and vascular cancer embolus. CONCLUSION: Independent risk factors for gastric cancer recurrence following radical surgery were utilized to construct a nomogram for predicting early relapse. This nomogram effectively assesses the risk of recurrence, aids in treatment decision-making and follow-up planning in clinical settings, and demonstrated strong performance in the validation cohort.

Boarding Oncolytic Viruses onto Tumor-Homing Bacterium-Vessels for Augmented Cancer Immunotherapy.

Oncolytic viruses (OVs) have been widely used as anticancer therapeutics because of their systemic immune responses during viral replication. However, the low enrichment of OVs within tumors and limited immune activation have hindered their clinical application. Herein, we proposed the concept of bacteria-assisted targeting of OVs to tumors, with liposome-cloaked oncolytic adenoviruses (OAs) conjugated onto tumor-homing Escherichia coli BL21 (designated as E. coli-lipo-OAs) for enhanced cancer immunotherapy. Notably, the enrichment of OAs transported by self-propelled bacterial microbe vehicles in E. coli-lipo-OAs in a nonsmall cell lung tumor can be potentiated by more than 170-fold compared with that of intravenously injected bare OAs. In vivo studies further revealed that E. coli-lipo-OAs administered intravenously significantly enhanced antitumor immunity through bacterial-viral-augmented immune responses. Our findings suggest that the self-driving microbe vehicle as a systemic delivery system for OVs can be a potent platform for developing future anticancer biotherapeutics at the clinical level.

LMOD1, an oncogene associated with Lauren classification, regulates the metastasis of gastric cancer cells through the FAK-AKT/mTOR pathway.

BACKGROUND: The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. METHODS: We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data. RESULTS: The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 1016). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor. CONCLUSION: LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer.

A novel pN3 gastric cancer staging system with superior prognostic utility based upon the examination of over 31 lymph nodes: a propensity score-matching analysis.

BACKGROUND: Individuals with pN3 gastric cancer (GC) account for a large proportion of pN + GC, and exhibit poor survival outcomes. The pN3 stage is defined based upon the number of metastatic lymph nodes (mLNs), but the subclassification of pN3 patients based upon the number of examined LNs (eLNs) is rarely performed. METHODS: In total, 2894 pTxN3M0 GC patients in the Surveillance, Epidemiology, and End Results database that had undergone surgery from 2000 to 2016 were selected for analysis. The X-tile software was used to select the optimal cutoff values. Cox proportional regression analyses were used to evaluated hazard ratios corresponding to the risk of death. Selection bias was minimized via propensity score matching (PSM). RESULTS: As the number of eLNs rose, the risk of death for patients trended downwards. Survival analyses indicated that patients with ≤ 31 eLNs exhibited significantly poorer survival outcomes as compared to patients with > 31 eLNs (5-year OS: 18.4% vs. 24.7%), and this result remained significant when analyzing 857 pairs of patients following PSM analysis. Significant differences in prognosis were additionally observed when comparing pN3a and pN3b patients with ≤ 31 or > 31 eLNs under pT3/4a stage. For pT4b stage, pN3a patients with > 31 eLNs also exhibited a better prognosis than other patients. The novel TNM staging system designed exhibited excellent utility as a tool for the prognostic evaluation of this GC patient population. CONCLUSIONS: These results suggest that in pN3 GC, a minimum of 32 LNs should be examined. The novel TNM staging system for pN3 patients described herein, which was developed based upon the number of eLNs, may thus be of value in clinical settings.

A research of STEAP1 regulated gastric cancer cell proliferation, migration and invasion in vitro and in vivos.

Six-Transmembrane Epithelial Antigene of the Prostate 1 (STEAP1) is associated with the occurrence and development of cancer. This study aimed to clarify the role of STEAP1 in gastric cancer tumour growth and metastasis, as well as its molecular mechanism of action.Statistical methods were used for clinical data analysis. Protein expression was detected using immunohistochemistry(IHC). The mRNA and protein expression in the cell cultures were detected using reverse transcription-polymerase chain reaction(RT-PCR) and western blot analysis. Overexpression and silencing models were constructed using plasmid and lentivirus transfection. To detect cell proliferation in vitro, Cell Counting Kit-8(CCK-8), flow cytometry and colony formation assays were used; transwell and wound healing assays were used to detect cell migration and invasion;For in vivo experiments, nude BALB/c mice were used for detecting subcutaneous tumorigenesis and intraperitoneal implantation. In the results,we found STEAP1 was overexpressed in gastric cancer tissues and cell lines. Single-factor and Cox analyses showed that STEAP1 gene expression level correlated with poor prognosis. Up-regulation of STEAP1 increased cell proliferation, migration and invasion, which decreased after STEAP1 was knocked down. These changes were achieved via the activation of the AKT/FoxO1 pathway and epithelial-mesenchymal transformation (EMT). The in vivo animal experiments showed that STEAP1 knock down, resulted in a decrease in the subcutaneous tumour and peritoneal tumour formation.

Influences of In-Furnace Kaolin Addition on the Formation and Emission Characteristics of PM2.5 in a 1000 MW Coal-Fired Power Station.

The impacts of in-furnace kaolin addition on the formation and emission characteristics of PM2.5 from a 1000 MW coal-fired utility boiler equipped with electrostatic precipitators (ESPs) are investigated for the first time ever in this contribution. Detailed characterization of the chemical composition, micromorphology, melting characteristics of the fine PM, total fly ash, and/or bottom ash samples were carried out using the X-ray fluorescence probe, the field emission scanning electron microscope coupled with an energy dispersive X-ray detector, the ash fusion analyzer, and the dust specific resistivity analyzer. The results showed that the formation of fine PM was reduced when kaolin was added, and the mass concentrations of the particulate matter with the aerodynamic diameters of ≤0.3 and 2.5 µm (PM0.3 and PM2.5) were reduced by 55.97% and 5.48%, respectively. As expected, kaolin reacted with the volatile mineral vapors (e.g., Ca, Na) and inhibited their partitioning into ultrafine PM. It was interesting to find that the added kaolin modified the ash melting behavior, and promoted the capture of the ultrafine PM onto the coarse particles. What is more, the added kaolin reduced the specific resistivity of the fly ash and improved their capture efficiency in the ESPs. Finally, the above combined effects brought about the emission reductions of 41.27% and 36.72% for PM0.3 and PM2.5 after the ESPs. These results provided a direct confirmation on the feasibility of in-furnace kaolin addition on the PM reduction in the realistic combustion conditions.

Source Localization in Acoustic Sensor Networks via Constrained Least-Squares Optimization Using AOA and GROA Measurements.

A constrained least-squares (CLS) 3D source localization method is presented for acoustic sensor networks with sensor position errors. The proposed approach uses angles of arrivals (AOAs) and gain ratios of arrival (GROAs) measured simultaneously at each node to estimate the source position jointly. Compared to AOA-only localization methods, the GROAs can be used in conjunction with AOA measurements so as to get more accurate results by exploiting the geometrical relationship between these two measurements. Compared to time difference of arrival localization methods, the proposed algorithm does not require accurate time synchronization over different nodes. The theoretical mean-square error matrices of the proposed approach are derived and they are exactly equal to the Cramér-Rao bound for Gaussian noise under the small error condition. Simulations validate the performance of the proposed estimator.

Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation on Cerebral Hemodynamics in Patients with Disorders of Consciousness: A Sham-Controlled Study.

OBJECTIVE: This study aimed to determine the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) on cerebral hemodynamics in patients with disorders of consciousness (DOC). METHODS: In this sham-controlled study, 20-Hz and sham rTMS were applied over the left primary motor cortex (M1) of 5 patients in a vegetative state (VS) and 5 patients in a minimally conscious state (MCS). The clinical behavior and cerebral blood flow (CBF) velocity in the bilateral middle cerebral artery (MCA) of the patients were evaluated before and after rTMS. RESULTS: Compared with the VS group, the MCS group exhibited significant increases in peak systolic velocity (PSV; p = 0.024) and mean flow velocity (MFV) of the left MCA that were temporally related to the rTMS (p = 0.042). There were no significant effects on CBF velocity in the sham-stimulation group or the right MCA. CONCLUSIONS: High-frequency rTMS exerts different effects on CBF depending on the level of consciousness in patients with DOC such that it increased PSV and MFV in patients in a MCS. These effects may be related to the varying degrees of disrupted neurovascular coupling and the autonomic control of the cerebral hemodynamics in patients in a VS or MCS.

Modeling transient sound propagation over an absorbing plane by a half-space interpolated time-domain equivalent source method.

A half-space interpolated time-domain equivalent source method (ITDESM) is proposed to model the transient sound propagation over an absorbing plane. In this approach, a closed-form transient half-space Green's function (i.e., the impulse response function in three-dimensional space) for a pure absorbing infinite plane is introduced to develop the half-space ITDESM formulation. Instead of the free transient Green's function employed in the conventional ITDESM, such Green's function contains the reflection effect of the absorbing plane. As a numerical example, reconstructing the transient pressure fields from two monopole sources is depicted, where both monopoles are located in front of an infinite plane with absorbing impedance. Simulation results indicate that the half-space ITDESM can reconstruct the half-space transient sound fields in both the space and time domains very well. The proposed method is also investigated by taking into account the measurement noise in the reconstruction process. An experiment of an impacted steel plate above a glass wool board is presented to illustrate the validity of the proposed method under actual conditions.

Burdens of stomach and esophageal cancer from 1990 to 2019 and projection to 2030 in China: Findings from the 2019 Global Burden of Disease Study.

Background: Stomach and esophageal cancer exhibit high morbidity and mortality rate in China, resulting in substantial disease burdens. It is imperative to identify the temporal trends of stomach and esophageal cancer from 1990 to 2019 and project future trends until 2030, which can provide valuable information for planning effective management and prevention strategies. Methods: We collected and analysed data from the Global Burden of Disease (GBD) between 1990 and 2019, including incidence, mortality, disability-adjusted life years (DALYs), age-standardised incidence rate (ASIR), mortality rate (ASMR) and DALYs rate. We also calculated and reported the proportion of mortality and DALYs attributable to risk factors by sex in China and different regions. The Bayesian age-period-cohort model was applied to project future trends until 2030. Results: The new cases, deaths and DALYs of stomach and esophageal cancer increased from 1990 to 2019. However, the ASIR, ASMR and age-standardised DALYs rates for stomach and esophageal cancer all decreased during the same period. These changes may be related to risks, such as smoking and diet. Furthermore, we utilised the projection model to estimate that the ASIR and ASMR of stomach and esophageal cancer among females will likely follow steady downward trends, while the ASMR of stomach cancer among males is expected to exhibit a significant decline. However, the ASIR of stomach and esophageal cancer and the ASMR of esophageal cancer among males are projected to display slight upward trends until 2030. Conclusions: The analysis of stomach and esophageal cancer trends in China from 1990 to 2030 reveals a general decline. However, it is crucial to acknowledge the persistent high burden of both cancers in the country. Adopting healthy lifestyle practices, including the reduction of tobacco and alcohol intake, avoidance of moldy foods and increased consumption of fresh fruits and vegetables can contribute to mitigating the risk of stomach and esophageal cancer. Significantly, the formulation and implementation of well-founded and efficacious public health policies are imperative for alleviating the disease burden in China.

Characterization of RNA modifications in gastric cancer to identify prognosis-relevant gene signatures.

BACKGROUND: Most human genes have diverse transcript isoforms, which mainly arise from alternative cleavage and polyadenylation (APA) at 3' ends. N7-methylguanosine (m7 G) is also an essential epigenetic modification at the 5' end. However, the contribution of these two RNA modifications to the development, prognosis, regulation mechanisms, and drug sensitivity of gastric cancer (GC) is unclear. METHODS: The expression data of 2412 patients were extracted from 12 cohorts and the RNA modification patterns of 20 marker genes were systematically identified into phenotypic clusters using the unsupervised clustering approach. Following that, we developed an RNA modification model (RMscore) to quantify each GC patient's RNA modification index. Finally, we examined the correlation between RMscore and clinical features such as survival outcomes, molecular subtypes identified by the Asian Cancer Research Group (ACRG), posttranscriptional regulation, and chemotherapeutic sensitivity in GC. RESULTS: The samples were categorized into two groups on the basis of their RMscore: high and low. The group with a low RMscore had a bad prognosis. Moreover, the low RMscore was associated with KRAS, Hedgehog, EMT, and TGF-ß signaling, whereas a high RMscore was related to abnormal cell cycle signaling pathway activation. The findings also revealed that the RMscore contributes to the regulation of the miRNA-mRNA network. Drug sensitivity analysis revealed that RMscore is associated with the response to some anticancer drugs. CONCLUSIONS: The RMscore model has the potential to be a useful tool for prognosis prediction in patients with GC. A comprehensive investigation of APA-RNA and m7 G-RNA modifications may reveal novel insights into the epigenetics of GC and aid in the development of more effective treatment strategies.

A Novel Method for Dynamically Assessing the Prognosis of Patients with pT1 Gastric Cancer: A Large Population-Based Dynamic Prognostic Analysis.

Background: While early gastric cancer (EGC) patients are likely to experience relatively long postoperative survival, certain disease-related findings are associated with a poorer prognosis. This study sought to develop and validate a novel predictive model capable of estimating conditional disease-specific survival (CDSS) in EGC patients. Methods: A total of 3016 patients diagnosed with pT1NxM0 GC after gastrectomy between 1998 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database and were separated into training and validation cohorts. Kaplan‒Meier curves and log-rank tests were employed to evaluate DSS, after which univariate and multivariate Cox regression analyses were used to construct a predictive nomogram and to estimate CDSS at 1, 2, and 3 years postoperatively in these patients. Results: In the training cohort, the 3-year CDSS rose from 89.1% to 94.6% from 0 to 5 years postoperatively, while the 5-year CDSS rose from 84.5% to 92.0%. Cox regression analyses led to the construction of a nomogram that was able to reliably predict 3- and 5-year CDSS at 1, 2, and 3 years postoperatively (all P < 0.05) based upon patient age, tumor size, pT stage, pN stage, and the number of retrieved lymph nodes. This model exhibited good discriminative power in the training and validation cohorts (concordance index: 0.791 and 0.813, respectively), and nomogram calibration curves confirmed that actual and predicted survival outcomes were close to one another. Conclusions: We herein developed a nomogram capable of accurately predicting the CDSS of EGC patients that had survived for multiple years after undergoing surgery.

Design and Synthesis of Low Surface Energy Coating with Functionalized Al2O3 Nanoparticles.

In a high-moisture environment where dust and coastal saltwater are prevalent, the stability of power equipment can be adversely affected. This issue can result in equipment downtime, particularly for transformers, severely disrupting the continuous operation of DC transmission systems. To address this challenge, a superhydrophobic modified fluorosilicone coating was developed, incorporating anti-stain properties. To tackle this issue comprehensively, an orthogonal experiment was conducted, involving six factors and three levels. The study focused particularly on assessing the impact of water-repellent recovery agents, nanofillers, antistatic agents, anti-mold agents, leveling agents, as well as wetting and dispersing agents on the coating's surface tension. The results demonstrate that selecting an appropriate base resin and incorporating well-matched functional additives played a central role in effectively reducing the surface tension of the coating. Consequently, optimized coatings exhibited exceptional resistance to stains and displayed strong corrosion resistance.

Fabrication of a Fluorocarbon Low Surface Energy Coating for Anti-Stain Applications.

In the long-term working state, stains such as dust, oil, and charged particles in the environment are prone to deposit on the surface of the power equipment, which has great security risks. To achieve anti-stain performance, fluorocarbon composite coating with a low surface energy was prepared and studied. In this paper, SiO2 nanoparticles were used as inorganic fillers and fluorocarbon resin was used as the substrate to form anti-stain coatings. By adjusting and optimizing the ratio of fillers and organic resins, coatings with different static contact angles were constructed. The optimum composite coating has a contact angle of 151 ± 2° and a surface energy of 9.6 mJ/m2. After high-temperature treatment (up to 200 °C), immersion in corrosive solutions (pH 3-11), and sandpaper abrasion (after 5 abrasion cycles), the coating has been proven to show good thermal, chemical and mechanical stability. Our study provides significant research and market opportunities for the anti-stain application of the fluorocarbon composite coating on power equipment.

Engineered bacterial outer membrane vesicles encapsulating oncolytic adenoviruses enhance the efficacy of cancer virotherapy by augmenting tumor cell autophagy.

Oncolytic adenovirus (Ad) infection promotes intracellular autophagy in tumors. This could kill cancer cells and contribute to Ads-mediated anticancer immunity. However, the low intratumoral content of intravenously delivered Ads could be insufficient to efficiently activate tumor over-autophagy. Herein, we report bacterial outer membrane vesicles (OMVs)-encapsulating Ads as microbial nanocomposites that are engineered for autophagy-cascade-augmented immunotherapy. Biomineral shells cover the surface antigens of OMVs to slow their clearance during in vivo circulation, enhancing intratumoral accumulation. After entering tumor cells, there is excessive H2O2 accumulation through the catalytic effect of overexpressed pyranose oxidase (P2O) from microbial nanocomposite. This increases oxidative stress levels and triggers tumor autophagy. The autophagy-induced autophagosomes further promote Ads replication in infected tumor cells, leading to Ads-overactivated autophagy. Moreover, OMVs are powerful immunostimulants for remolding the immunosuppressive tumor microenvironment, facilitating antitumor immune response in preclinical cancer models in female mice. Therefore, the present autophagy-cascade-boosted immunotherapeutic method can expand OVs-based immunotherapy.

Virus-Protein Corona Replacement Strategy to Improve the Antitumor Efficacy of Intravenously Injected Oncolytic Adenovirus.

Intravenous administration of oncolytic adenoviruses (OVs) is a hopeful tumor therapeutic modality. However, the sharp clearance of OVs by the immune system dampens its effectiveness. Many studies have attempted to extend the circulation of intravenously administered OVs, almost all by preventing OVs from binding to neutralizing antibodies and complements in the blood, but the results have not been satisfactory. In contrast to previous conclusions, we found that the key to improving the circulation of OVs is to prevent the formation of the virus-protein corona rather than simply preventing the binding of neutralizing antibodies or complements to OVs. After identifying the key protein components of the virus-protein corona, we proposed a virus-protein corona replacement strategy, where an artificial virus-protein corona was formed on OVs to completely prevent the interaction of OVs with key virus-protein corona components in the plasma. It was found that this strategy dramatically prolonged the circulation time of OVs by over 30 fold and increased the distribution of OVs in tumors by over 10-fold, resulting in superior antitumor efficacy in primary and metastatic tumor models. Our finding provides a perspective on intravenous delivery of OVs, shifting the focus of future studies from preventing OV binding with neutralization antibodies and complements to preventing OVs from interacting with key virus-protein corona components in the plasma.

FN1 mRNA 3'-UTR supersedes traditional fibronectin 1 in facilitating the invasion and metastasis of gastric cancer through the FN1 3'-UTR-let-7i-5p-THBS1 axis.

Background: Current clinical treatments for gastric cancer (GC), particularly advanced GC, lack infallible therapeutic targets. The 3'-untranslated region (3'-UTR) has attracted increasing attention as a drug target. Methods: In vitro and in vivo experiments were conducted to determine the function of FN1 3'-UTR and FN1 protein in invasion and metastasis. RNA pull-down assay and high-throughput sequencing were used to screen the factors regulated by FN1 3'-UTR and construct the regulatory network. Western blotting and polymerase chain reaction were used to examine the correlation of intermolecular expression levels. RNA-binding protein immunoprecipitation was used to verify the correlation between FN1 3'-UTR and target mRNAs. Results: The FN1 3'-UTR may have stronger prognostic implications than the FN1 protein in GC patients. Upregulation of FN1 3'-UTR significantly promoted the invasive and metastatic abilities of GC cells to a greater extent than FN1 protein in vitro and in vivo. A novel regulatory network was constructed based on the FN1 3'-UTR-let-7i-5p-THBS1 axis, wherein FN1 3'-UTR displayed stronger oncogenic effects than the FN1 protein. Conclusions: FN1 3'-UTR may be a better therapeutic target for constructing targeted drugs in GC than the FN1 protein.

The role of macrophages in gastric cancer.

As one of the deadliest cancers of the gastrointestinal tract, there has been limited improvement in long-term survival rates for gastric cancer (GC) in recent decades. The poor prognosis is attributed to difficulties in early detection, minimal opportunity for radical resection and resistance to chemotherapy and radiation. Macrophages are among the most abundant infiltrating immune cells in the GC stroma. These cells engage in crosstalk with cancer cells, adipocytes and other stromal cells to regulate metabolic, inflammatory and immune status, generating an immunosuppressive tumour microenvironment (TME) and ultimately promoting tumour initiation and progression. In this review, we summarise recent advances in our understanding of the origin of macrophages and their types and polarisation in cancer and provide an overview of the role of macrophages in GC carcinogenesis and development and their interaction with the GC immune microenvironment and flora. In addition, we explore the role of macrophages in preclinical and clinical trials on drug resistance and in treatment of GC to assess their potential therapeutic value in this disease.

RBPMS2, as a novel biomarker for predicting lymph node metastasis, guides therapeutic regimens in gastric cancer.

RNA-binding protein with multiple splicing 2 (RBPMS2) is a critical gene that encodes a member of the RNA-recognition-motif-containing protein family and is involved in the development and dedifferentiation of digestive smooth muscle cells. However, whether RBPMS2 has an effect on the prognosis of gastric cancer (GC) and its possible mechanism during GC progression remain unknown. Here, we collected 596 GC patients who underwent curative surgical resection to evaluate expression of RBPMS2. RBPMS2 was upregulated in GC tissues, and was associated with lymph node metastasis. We analysis the KEGG pathway and GO biological processes, cellular component and molecular function of RBPMS2 interactive genes, as well as RBPMS2-binding partner ESRP1 interactive genes. We also focus on the correlation analysis between EMT-related genes and RBPMS2/ESRP1. Finally, we analysed the correlation between RBPMS2 expression and chemotherapeutic drugs which may assist in GC therapy and demonstrated that RBPMS2 expression was associated with tumour mutation burden (TMB) and Microsatellite Instability (MSI), as well as immune infiltration level in GC.

The SKA3-DUSP2 Axis Promotes Gastric Cancer Tumorigenesis and Epithelial-Mesenchymal Transition by Activating the MAPK/ERK Pathway.

Background: Spindle and kinetochore-related complex subunit 3 (SKA3), a member of the SKA family of proteins, is associated with the progression of multiple cancers. However, the role of SKA3 in gastric cancer has not been studied. Methods: The expression levels of SKA3 and dual-specificity phosphatase 2 (DUSP2) proteins were detected by immunohistochemistry. The effects of SKA3 and DUSP2 on the proliferation, migration, invasion, adhesion, and epithelial-mesenchymal transition of gastric cancer were studied in vitro and in vivo. Results: Immunohistochemical analysis of 164 cases of gastric cancer revealed that high expression of SKA3 was negatively correlated with DUSP2 expression and related to N stage, peritoneal metastasis, and poor prognosis. In vitro studies showed that silencing SKA3 expression inhibited the proliferation, migration, invasion, adhesion and epithelial-mesenchymal transition of gastric cancer. In vivo experiments showed that silencing SKA3 inhibited tumor growth and peritoneal metastasis. Mechanistically, SKA3 negative regulates the tumor suppressor DUSP2 and activates the MAPK/ERK pathway to promote gastric cancer. Conclusion: Our results indicate that the SKA3-DUSP2-ERK1/2 axis is involved in the regulation of gastric cancer progression, and SKA3 is a potential therapeutic target for gastric cancer.