An atlas on risk factors for gastrointestinal cancers: A systematic review of Mendelian randomization studies.

OBJECTIVE: Gastrointestinal cancers are one of the most frequent cancer types and seriously threaten human life and health. Recent studies attribute the occurrence of gastrointestinal cancers to both genetic and environmental factors, yet the intrinsic etiology remains unclear. Mendelian randomization is a powerful well-established statistical method that is based on genome-wide association study (GWAS) to evaluate the causal relationship between exposures and outcomes. In the present study, we aimed to conduct a systematic review of Mendelian randomization studies investigating any causal risk factors for gastrointestinal cancers. METHODS: We systematically searched Mendelian randomization studies that addressed the associations of genetically predicted exposures with five main gastrointestinal cancers from September 2014 to March 2024, as well as testing the research quality and validity. RESULTS: Our findings suggested robust and consistent causal effects of body mass index (BMI), basal metabolic rate, fatty acids, total cholesterol, total bilirubin, insulin like growth factor-1, eosinophil counts, interleukin 2, alcohol consumption, coffee consumption, apolipoprotein B on colorectal cancer risks, BMI, waist circumference, low-density lipoprotein (LDL), total testosterone, smoking on gastric cancer risks, BMI, fasting insulin, LDL, waist circumference, visceral adipose tissue (VAT), immune cells, type 2 diabetes mellitus (T2DM) on pancreatic cancer risks, waist circumference, smoking, T2DM on esophageal adenocarcinoma risks, and VAT, ferritin, transferrin, alcohol consumption, hepatitis B virus infection, rheumatoid arthritis on liver cancer risks, respectively. CONCLUSION: Larger, well-designed Mendelian randomization studies are practical in determining the causal status of risk factors for diseases.

Shared genetic basis and causality between schizophrenia and inflammatory bowel disease: evidence from a comprehensive genetic analysis.

BACKGROUND: The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders. RESULTS: SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07­1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06­1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04­1.18, p = 1.84 × 10−3). CONCLUSIONS: We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

Diagnosis of colorectal cancer based on folate receptor-positive circulating tumor cell analysis: a retrospective cohort study.

BACKGROUND: Early diagnosis and treatment are crucial to improve the prognosis of colorectal cancer (CRC). At present, there is a lack of an accurate CRC screening factor. We conducted folate receptor-positive circulating tumor cell analysis (FR + CTC analysis) in distinguishing CRC from benign colorectal diseases to evaluate the diagnostic efficiency. METHODS: Clinical data of patients admitted to The First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were retrospectively collected. Levels of FR + CTC and other indicators were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of these molecular biomarkers. RESULTS: Data of 103 patients with CRC and 54 patients with benign colorectal diseases were collected. FR + CTC levels were observed significantly higher in CRC patients than in patients with benign colorectal diseases (P < 0.001). FR + CTC level was correlated with tumor diameter, differentiation, T-stage, pathological stage, clinical stage, and intravascular tumor thrombus in patients with CRC (P < 0.05). The optimal cutoff value of FR + CTC level for diagnosing CRC patients was 7.66 FU/3 ml, with a sensitivity of 85.4%, a specificity of 74.1%, and an Area Under Curve (AUC) of 0.855 (95% CI 0.77-0.923). In < 50-years old patients with CRC, the diagnostic efficiency of FR + CTC was excellent, with an AUC of 0.936 (95% CI 0.877-0.995). CONCLUSION: FR + CTC counting has excellent diagnostic efficiency in screening of CRC. FR + CTC count can also predict the tumor stage of CRC patients before surgery, and guide the choice of treatment.

Bibliometric analysis of extracorporeal shock wave therapy for tendinopathy.

BACKGROUND: Extracorporeal shock wave therapy (ESWT) is a mature, conservative treatment modality for tendinopathy. Although many relevant studies have been conducted, systematic bibliometric studies are lacking. This study aimed to identify trends and hotspots in the treatment of tendinopathy using ESWT. METHODS: A literature search was conducted on ESWT for tendinopathy using the Web of Science Core Collection with a search period of 2002 to 2022. Of 559 identified studies, 276 met the inclusion criteria and were analyzed using CiteSpace software. RESULTS: The results showed that from 2002 to 2022, the publication rate of literature on ESWT for tendinopathy was generally increasing. Research hotspots, such as tendinopathy and calcific rotator cuff deposits, began earlier but continued to receive scholarly attention. Research on animal models and molecular mechanisms has progressed slowly in this field. The combined or comparative effectiveness of injectable and supplement-based treatments with ESWT is a popular research topic. CONCLUSION: Pain management in patients with tendinopathy has received considerable attention. Simultaneously, more clinical indicators of energy levels and pulse parameters during ESWT are needed to provide more scientific and accurate treatment for patients.

Correction to "Interleukin-34 promotes the proliferation and epithelial-mesenchymal transition of gastric cancer cells".

[This corrects the article on p. 1968 in vol. 14, PMID: 36310707.].

Escherichia coli-Based In Situ Triggerable Probe as an Amplifier for Sensitive Diagnosis and Penetrated Therapy of Cancer.

Escherichia coli (E. coli) was used for cancer therapy due to the tumor-targeting, catalytic, and surface-reducing properties. Effective diagnosis combined with treatment of cancer based on E. coli, however, was rarely demonstrated. In this study, E. coli was used to surface reduce HAuCl4 and as a carrier to modify riboflavin (Rf) and luminol (E-Au@Rf@Lum). After targeted delivery to tumor, the E-Au@Rf@Lum probe could actively emit 425 nm blue-violet chemiluminescence (CL) to achieve cell imaging for cancer diagnosis. Furthermore, this light could in situ trigger the photosensitizer (Rf) through CL resonance energy transfer, which produces reactive oxygen species (ROS) for accurate photodynamic therapy. In return, the excessive ROS enhanced the blue-violet light which was further absorbed by Rf, and ROS production was cyclically amplified. Abundant ROS broke down the dense extracellular matrix network and penetrated deep into tumors. Besides, E. coli with excellent catalytic property could decompose H2O2 to O2 to relieve tumor hypoxia for a long time and enhance the photosensitized process of Rf. By self-illumination, effective penetration, and tumor hypoxia relief, this work opens a self-amplified therapy modality to tumor.

Prediction of overall survival after radical gastrectomy using nomograms created by tumor markers.

Prediction of prognosis after radical resection of gastric cancer has not been well established. Therefore, we aimed to establish a prognostic model based on a new score system of patients with gastric cancer. A total of 1235 patients who underwent curative gastrectomy at our hospital from October 2015 to April 2017 were included in this study. Univariate and multivariate analyses were used to screen for prognostic risk factors. Construction of the nomogram was based on Cox proportional hazard regression models. The construction of the new score models was analyzed by the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve. Multivariate analysis showed that tumor size, T, N, carcinoembryonic antigen, CA125, and CA19-9 were independent prognostic factors. The new score model had a greater AUC (The area under the ROC curve) than other systems, and the C-index of the nomogram was highly reliable for evaluating the survival of patients with gastric cancer. Based on the tumor markers and other clinical indicators, we developed a precise model to predict the prognosis of patients with gastric cancer after radical surgery. This score system can be helpful to both surgeons and patients.

Effects and mechanisms of trifluridine alone or in combination with cryptotanshinone in inhibiting malignant biological behavior of gastric cancer.

BACKGROUND: The incidence of gastric cancer (GC) ranks fourth among all malignant tumors worldwide, and the fatality rate ranks second among all malignant tumors. Several Chinese traditional medicines have been used in the treatment of advanced gastric cancer. This study aims to investigate the effect of combinational use of natural product cryptotanshinone (CTS) with anti-cancer drug trifluorothymidine (FTD) in GC. METHODS: Cell Counting Kit-8 assay was used to detect the inhibitory effect of the combinational or separate use of FTD and CTS on the growth of HGC-27 and AGS GC cells. The combined index of FTD and CTS was calculated using CompuSyn software. To understand the mechanism, we applied flow cytometry to study the cell cycle and cell apoptosis after treatment. We also investigated the amount of FTD incorporated into the DNA by immunofluorescence assay. The expression of relevant proteins was monitored using western blot. Furthermore, the effect of using TAS-102 in combination with CTS was studied in xenograft tumor nude mice model. RESULTS: FTD and CTS inhibited the growth of GC cells in a dose-dependent manner, respectively. They both exhibited low to sub-micromolar potency in HGC-27 and AGS cells. The combination of FTD and CTS showed synergistic anticancer effect in HGC-27 cells and AGS cells. Our mechanism studies indicate that FTD could block HGC-27 cells at G2/M phase, while CTS could block HGC-27 cells at G1/G0 phase, while FTD combined with CTS could mainly block HGC-27 cells at G2 phase. FTD in combination with CTS significantly increased the apoptosis of HGC-27 cells. We observed that CTS treatment increased the incorporation of FTD into the DNA HGC-27 cell. FTD treatment activated STAT3 phosphorylation in HGC-27 cells, while CTS treatment down-regulated the concentration of p-STAT3. Interestingly, the combination of CTS and FTD reduced STAT3 phosphorylation induced by FTD. In the in vivo experiments, we observed that the combination of TAS-102 with CTS was significantly more potent than TAS-102 on tumor growth inhibition. CONCLUSIONS: FTD combined with CTS has a synergistic anti-gastric cancer effect as shown by in vitro and in vivo experiments, and the combined treatment of FTD and CTS will be a promising treatment option for advanced gastric cancer.

Efficacy and outcome of extensive intraoperative peritoneal lavage plus surgery vs surgery alone with advanced gastric cancer patients.

BACKGROUND: Gastric cancer (GC) is one of the most common malignant tumors. After resection, one of the major problems is its peritoneal dissemination and recurrence. Some free cancer cells may still exist after resection. In addition, the surgery itself may lead to the dissemination of tumor cells. Therefore, it is necessary to remove residual tumor cells. Recently, some researchers found that extensive intraoperative peritoneal lavage (EIPL) plus intraperitoneal chemotherapy can improve the prognosis of patients and eradicate peritoneal free cancer for GC patients. However, few studies explored the safety and long-term outcome of EIPL after curative gastrectomy. AIM: To evaluate the efficacy and long-term outcome of advanced GC patients treated with EIPL. METHODS: According to the inclusion and exclusion criteria, a total of 150 patients with advanced GC were enrolled in this study. The patients were randomly allocated to two groups. All patients received laparotomy. For the non-EIPL group, peritoneal lavage was washed using no more than 3 L of warm saline. In the EIPL group, patients received 10 L or more of saline (1 L at a time) before the closure of the abdomen. The surviving rate analysis was compared by the Kaplan-Meier method. The prognostic factors were carried out using the Cox appropriate hazard pattern. RESULTS: The basic information in the EIPL group and the non-EIPL group had no significant difference. The median follow-up time was 30 mo (range: 0-45 mo). The 1- and 3-year overall survival (OS) rates were 71.0% and 26.5%, respectively. The symptoms of ileus and abdominal abscess appeared more frequently in the non-EIPL group (P < 0.05). For the OS of patients, the EIPL, Borrmann classification, tumor size, N stage, T stage and vascular invasion were significant indicators. Then multivariate analysis revealed that EIPL, tumor size, vascular invasion, N stage and T stage were independent prognostic factors. The prognosis of the EIPL group was better than the non-EIPL group (P < 0.001). The 3-year survival rate of the EIPL group (38.4%) was higher than the non-EIPL group (21.7%). For the recurrence-free survival (RFS) of patients, the risk factor of RFS included EIPL, N stage, vascular invasion, type of surgery, tumor location, Borrmann classification, and tumor size. EIPL and tumor size were independent risk factors. The RFS curve of the EIPL group was better than the non-EIPL group (P = 0.004), and the recurrence rate of the EIPL group (24.7%) was lower than the non-EIPL group (46.4%). The overall recurrence rate and peritoneum recurrence rate in the EIPL group was lower than the non-EIPL group (P < 0.05). CONCLUSION: EIPL can reduce the possibility of perioperative complications including ileus and abdominal abscess. In addition, the overall survival curve and RFS curve were better in the EIPL group.

Comprehensive analysis of the biological function and immune infiltration of SLC38A2 in gastric cancer.

BACKGROUND: Solute carrier family 38 member 2 (SLC38A2) has previously been reported to participate in carcinogenesis. However, its expression and function in gastric cancer (GC) remain unclear. The present study aimed to investigate the role of SLC38A2 in GC. METHODS: The prognostic value and expression of SLC38A2 in GC was analyzed by combining bioinformatics and experimental analyses. Colony formation, Cell Counting Kit-8, wound healing, Transwell and tumor formation assays were performed to assess the biological function of SLC38A2. The cBioPortal, GeneMANIA and LinkedOmics databases were mined to determine the underlying regulatory mechanisms of SLC38A2. The role of SLC38A2 in tumor immune infiltration was explored using the TIMER database. RESULTS: Our results demonstrated that SLC38A2 was upregulated and was correlated with a poor prognosis in GC patients. SLC38A2 downregulation significantly inhibited the proliferation, invasion and migration of GC cells. Abnormal genetic alteration and epigenetic regulation may contribute to the upregulation of SLC38A2 expression levels in GC. The results of enrichment analysis demonstrated that SLC38A2 was associated with 'hippo signaling' and 'ubiquitinyl hydrolase activity'. The results also indicated that SLC38A2 may be a key factor in GC immune infiltration and M2 macrophage polarization. CONCLUSION: Overall, these data identified that SLC38A2 may serve as a potential prognostic biomarker and therapeutic target in GC.

Development and validation of a novel nomogram for predicting overall survival in gastric cancer based on inflammatory markers.

BACKGROUND: Nearly 66% of occurrences of gastric cancer (GC), which has the second-highest death rate of all cancers, arise in developing countries. In several cancers, the predictive significance of inflammatory markers has been established. AIM: To identify clinical characteristics and develop a specific nomogram to determine overall survival for GC patients. METHODS: Nine hundred and four GC patients treated at the First Affiliated Hospital of Anhui Medical University between January 2010 and January 2013 were recruited. Prognostic risk variables were screened for Cox analysis. The C index, receiver operator characteristic (ROC) curve, and decision curve analysis were used to evaluate the nomogram. RESULTS: Tumor node metastasis stage, carcinoembryonic antigen, systemic immune-inflammation index, and age were identified as independent predictive variables by multivariate analysis. Systemic immune-inflammation index value was superior to that of other inflammatory indicators. The ROC indicated the nomogram had a higher area under the curve than other factors, and its C-index for assessing the validation and training groups of GC patients was extremely reliable. CONCLUSION: We created a novel nomogram to forecast the prognosis of GC patients following curative gastrectomy based on blood markers and other characteristics. Both surgeons and patients can benefit significantly from this new scoring system.

Cathodic Electrochemiluminesence Microscopy for Imaging of Single Carbon Nanotube and Nucleolin at Single Tumor Cell.

Cathodic electrochemiluminesence (ECL) microscopy based on luminol analog L012 was originally established to implement the imaging of a single nanotube and nucleolin on a single tumor cell. This microscopy utilizes multiwalled carbon nanotubes (MWCNTs) as advanced coreactant accelerators to efficiently convert dissolved oxygen (O2) and H2O2 into reactive oxygen species (ROS) due to excellent electrocatalytic properties. The produced ROS could oxide L012 into an excited state of L012 leading to a bright cathodic ECL illumination, thereby promoting ECL imaging of MWCNTs at a low triggering potential. After being modified with AS1411 aptamers, MWCNTs@AS1411 probes were incubated with tumor cells for specific ECL imaging of nucleolin on the plasma membrane, which permits cathodic ECL microscopy for label-free bioassays without ECL tags. The L012-based cathodic ECL microscopy with a moderate operating potential and label-free characteristics provides a universal approach in single nanomaterial and single-cell imaging and analyses.

A prognostic gene signature for gastric cancer and the immune infiltration-associated mechanism underlying the signature gene, PLG.

BACKGROUND: Globally, gastric cancer (GC) is a common and lethal solid malignant tumor. Identifying the molecular signature and its functions can provide mechanistic insights into GC development and new methods for targeted therapy. METHODS: Differentially expressed genes (DEGs) and prognostic genes (from univariate Cox regression analysis) were overlapped to obtain prognostic DEGs. Subsequently, molecular modules and the functions of these prognostic DEGs were identified by Metascape and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)/Gene Set Enrichment Analysis (GSEA) enrichment analyses, respectively. Protein-protein interaction (PPI) networks of up- and down-regulated prognostic DEGs in GC were analyzed using the MCC algorithm of the Cytohubba plug-in in Cytoscape. The prognostic gene signature was defined on hub genes of the PPI networks by least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. Furthermore, the expressional level of PLG in our clinical GC samples was validated by quantitative PCR (qPCR), western blotting, and immunohistochemistry (IHC). Subsequently, the PLG expression-correlation analysis was performed to assess the role of PLG in GC progression. Immune infiltration analysis was performed by single-sample gene set enrichment analysis (ssGSEA) to assess the inhibitory effect of PLG on immune infiltration. RESULTS: Firstly, Up- and down-regulated prognostic DEGs and hub genes in protein-protein interaction (PPI) networks in GC were identified. A prognostic five-gene signature (i.e., PLG, SPARC, FGB, SERPINE1, and KLHL41) was identified. Among the five genes, the relationship between plasminogen (PLG) and GC remains largely unclear. Moreover, the functions of PLG-correlated genes in GC, like 'fibrinolysis', 'hemostasis', 'ion channel complex', and 'transporter complex' were identified. In addition, PLG expression correlated negatively with the infiltration of almost all immune cell types. Interestingly, the expression of PLG was significantly and highly correlated with that of CD160, an immune checkpoint inhibitor. CONCLUSION: Our findings defined a new five-gene signature for predicting GC prognosis, but more validation is required to assess the effects and mechanism of the five genes, especially PLG, for the development of new GC therapies.

Interleukin-34 promotes the proliferation and epithelial-mesenchymal transition of gastric cancer cells.

BACKGROUND: Interleukin (IL)-34 is a pro-inflammatory cytokine involved in tumor development. The role of IL-34 in the proliferation and epithelial-mesenchymal transition (EMT) of gastric cancer (GC) remains to be investigated. AIM: To investigate whether and how IL-34 affects the proliferation of GC cells and EMT. METHODS: Using immunohistochemical staining, the expression of IL-34 protein was detected in 60 paired GC and normal paracancerous tissues and the relationship between IL-34 and clinicopathological factors was analyzed. The expression of IL-34 mRNA and protein in normal gastric epithelial cell lines and GC was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting, respectively. Stable IL-34 knockdown and overexpression in AGS cell lines were established by lentiviral infection and validated by qRT-PCR and western blotting. The cholecystokinin-8 assay, clone formation assay, cell scratch assay, and transwell system were used to detect GC cell proliferation, clone formation, migration, and invasion capacity, respectively. The effects of IL-34 on the growth of GC transplant tumors were assessed using a subcutaneous transplant tumor assay in nude mice. The effects of IL-34 on the expression level of EMT-associated proteins in AGS cells were examined by western blotting. RESULTS: Expression of IL-34 protein and mRNA was higher in GC cell lines than in GES-1 cells. Compared to matched normal paraneoplastic tissues, the expression of IL-34 protein was higher in 60 GC tissues, which was correlated with tumor size, T-stage, N-stage, tumor, node and metastasis stage, and degree of differentiation. Knockdown of IL-34 expression inhibited the proliferation, clone formation, migration, and invasion of AGS cells, while overexpression of IL-34 promoted cell proliferation, clone formation, migration, and invasion. Furthermore, the reduction of IL-34 promoted the expression of E-cadherin in AGS cells but inhibited the expression of vimentin and N-cadherin. Overexpression of IL-34 inhibited E-cadherin expression but promoted expression of vimentin and N-cadherin in AGS cells. Overexpression of IL-34 promoted the growth of subcutaneous transplanted tumors in nude mice. CONCLUSION: IL-34 expression is increased in GC tissues and cell lines compared to normal gastric tissues or cell lines. In GC cells, IL-34 promoted proliferation, clone formation, migration, and invasion by regulating EMT-related protein expression cells. Interference with IL-34 may represent a novel strategy for diagnosis and targeted therapy of GC.

Single-Site Fe-N-C Atom Based Carbon Nanotubes for Mutually Promoted and Synergistic Oncotherapy.

A carbon nanotube (CNT) supported single-site Fe-N-C catalyst (CNTs/Fe-N-C) exhibited attractive properties in peroxidase (POD)-like activity and photothermal effect. Herein, we designed a therapeutic platform by wrapping doxorubicin (DOX) in mesoporous CNTs/Fe-N-C with the cell membrane (CM) of breast cancer. The ultimate nanoagent (CNTs/Fe-N-C/DOX/CM) exhibited high antitumor activity on account of its efficient catalytic ability, increased drug release rates, and significant photothermal effect. Due to the POD-like activity, CNTs/Fe-N-C could effectively catalyze hydrogen peroxide (H2O2) into cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) of the tumor. Besides, the released DOX not only merely induced the diagnosis of the tumor cells for chemotherapy (CT) but also generated H2O2 to promote CDT. Moreover, the photothermal effect of the nanoagent could use for photothermal therapy (PTT). The increasing temperature was conducive to the release of DOX from micropore into the cell, which indirectly enhanced CT and CDT effects. As an intelligent and multifunctional drug delivery platform, the present CNTs/Fe-N-C/DOX/CM nanoagent could be engineered with synergistic treatments and favorable biosafety, which provides a promising paradigm in site-specific antitumor treatment and biomedicine.

Model established based on blood markers predicts overall survival in patients after radical resection of types II and III adenocarcinoma of the esophagogastric junction.

BACKGROUND: In recent years, the incidence of types II and III adenocarcinoma of the esophagogastric junction (AEG) has shown an obvious upward trend worldwide. The prognostic prediction after radical resection of AEG has not been well established. AIM: To establish a prognostic model for AEG (types II and III) based on routine markers. METHODS: A total of 355 patients who underwent curative AEG at The First Affiliated Hospital of Anhui Medical University from January 2014 to June 2015 were retrospectively included in this study. Univariate and multivariate analyses were performed to identify the independent risk factors. A nomogram was constructed based on Cox proportional hazards models. The new score models was analyzed by C index and calibration curves. The receiver operating characteristic (ROC) curve was used to compare the predictive accuracy of the scoring system and tumor-node-metastasis (TNM) stage. Overall survival was calculated using the Kaplan-Meier curve amongst different risk AEG patients. RESULTS: Multivariate analysis showed that TNM stage (hazard ratio [HR] = 2.286, P = 0.008), neutrophil-to-lymphocyte ratio (HR = 2.979, P = 0.001), and body mass index (HR = 0.626, P = 0.026) were independent prognostic factors. The new scoring system had a higher concordance index (0.697), and the calibration curves of the nomogram were reliable. The area under the ROC curve of the new score model (3-year: 0.725, 95% confidence interval [CI]: 0.676-0.777; 5-year: 0.758, 95%CI: 0.708-0.807) was larger than that of TNM staging (3-year: 0.630, 95%CI: 0.585-0.684; 5-year: 0.665, 95%CI: 0.616-0.715). CONCLUSION: Based on the serum markers and other clinical indicators, we have developed a precise model to predict the prognosis of patients with AEG (types II and III). The new prognostic nomogram could effectively enhance the predictive value of the TNM staging system. This scoring system can be advantageous and helpful for surgeons and patients.

A model established using marital status and other factors from the Surveillance, Epidemiology, and End Results database for early stage gastric cancer.

Currently, the postoperative prognosis of early stage gastric cancer (GC) is difficult to accurately predict. In particular, social factors are not frequently used in the prognostic assessment of early stage GC. Therefore, this study aimed to combine the clinical indicators and social factors to establish a predictive model for early stage GC based on a new scoring system. A total of 3647 patients with early stage GC from the Surveillance, Epidemiology, and End Results database were included in this study. A Kaplan-Meier survival analysis was used to compare differences in prognosis between different marital status, as an innovative prognostic indicator. Univariate and multivariate analyses were used to screen available prediction factors and then build a nomogram using the Cox proportional hazard regression model. The univariate analysis and multivariate analysis revealed that age at diagnosis, sex, histology, stage_T, surgery, tumor size, and marital status were independent prognostic factors of overall survival. Both the C-index and calibration curves confirmed that the nomogram had a great predictive effect on patient prognosis in training and testing sets. This nomogram based on clinical indicators and marital status can effectively help patients with early stage GC in the future.

SAMHD1, positively regulated by KLF4, suppresses the proliferation of gastric cancer cells through MAPK p38 signaling pathway.

SAMHD1 was reported to be related with the development of tumors, while its function in gastric cancer (GC) has not been elucidated yet. Here, we investigated the role and mechanism of SAMHD1 in regulating the proliferation of GC, as well as the mechanism of its expression regulation. Our results revealed that SAMHD1 was downregulated in GC tissues and cell lines, which was correlated with tumor size, depth of invasion and TNM stage. Overexpression of SAMHD1 inhibited the proliferation, clone formation, DNA synthesis and cell cycle progression, while knockdown of SAMHD1 promoted the proliferation of GC cells in vitro and vivo. Meanwhile, SAMHD1 inhibited the activation of MAPK p38 signaling pathway. Moreover, SB203580, as a MAPK p38 inhibitor, could reverse the proliferation and activation of MAPK p38 signaling pathway caused by knockdown of SAMHD1 in GC cells. Additionally, transcription factor Krüppel-like factor 4 (KLF4) bound to the core promoter of SAMHD1, increasing its transcriptional expression in GC cells. In conclusion, SAMHD1 suppressed the proliferation of GC through negatively regulating the activation of MAPK p38 signaling pathway and was upregulated by KLF4 in GC cells.

pH-programmed responsive nanoplatform for synergistic cancer therapy based on single atom catalysts.

The development of stimuli-responsive nanoplatform provides powerful tool for simultaneously enhancing the efficiency and accuracy of cancer therapies. Herein, we develop a pH-programmed responsive and synergistically theranostic nanoplatform based on CaCO3 mineralized single atom iron nanoparticles (SAF NPs). Basically, the highly active site on SAF NPs nanoagent can trigger in-situ produce toxic •OH in tumor microenvironment (TME) that kill cancer cells for Fenton-reaction-based chemodynamic therapy (CDT). The porous structure of SAF NPs can serve as delivery platforms to package and programmed release chemotherapeutic drug doxorubicin (DOX) to enhance chemotherapy (CT) efficiency. The nanoplatform was simultaneously in-situ mineralized with CaCO3 and A549 cell membrane (CM) which could avoid DOX leakage during transport in bloodstream and target homologous cancer cells. In addition, overload Ca2+ decomposed from CaCO3 triggers mitochondrial dysfunction, induces cytoskeleton collapse and oxidative stress to formulate calcium ions interference therapy (CIT). With the combination of CDT, CT and CIT, the designed multi-synergetic nanoplatform exhibits excellent biocompatibility, specificity and tunable drug release behavior, which has a broad application prospect in tumor therapy.

CircTMC5 promotes gastric cancer progression and metastasis by targeting miR-361-3p/RABL6.

BACKGROUND: Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC. METHODS: CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC). RESULTS: CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC. CONCLUSIONS: CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.