Gastric cancer is among the top five most important malignancies in the world due to the high burden of the disease and its lethality. Indeed, it is the fourth most common cause of death worldwide, characterized by a poor prognosis and low responsiveness to chemotherapy. Multidrug resistance limits the clinical management of the patient. Among these, the role of chronic activation of inflammatory pathways underlying gastric tumorigenesis should be highlighted. Furthermore, the gastric immunosuppressive TME influences the response to therapy. This review discusses the role of soluble cytokine receptors in the development and chemoresistance of gastric cancer, considered as a molecular marker and target of strategies to overcome resistance.

Nidus Vespae, an animal-derived traditional Chinese medicine, has a long-standing history in treating inflammatory conditions and tumor-related diseases. Notably, Nidus Vespae decoction (NVD) has been shown to inhibit the proliferation of gastric cancer cells, although the underlying mechanisms remain unclear.

This study aimed to elucidate the efficacy and mechanisms by which NVD exerts its therapeutic effects on gastric cancer.

We employed the Cell Counting Kit-8 (CCK-8) assay to assess the impact of NVD on gastric cancer cell proliferation, while flow cytometry was utilized to evaluate cell cycle arrest and apoptosis. Differentially expressed proteins (DEPs) were identified by proteomics analysis, which were further analyzed through Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Protein-protein interaction (PPI) analysis was conducted to identify the hub genes. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were conducted to assess mRNA and protein levels related to apoptosis, cell cycle regulation, and the JAK2/STAT3 pathway. Rescue experiments with Colivelin TFA confirmed the role of NVD in inhibiting gastric cancer cell proliferation. UPLC-HRMS and HS-SPME-GC-MS technologies were performed to analyze the composition of NVD, and the bioinformatics tool called BATMAN-TCM database was used for functional analyses.

Our results demonstrated that NVD significantly hindered the proliferation of gastric cancer cells, initiated programmed cell death, and induced cell cycle arrest in G2/M or G0/G1 phases in various gastric carcinoma cells in vitro. The identified DEPs were involved in several cancer-related pathways and signal transduction processes, notably the JAK-STAT receptor signaling pathway. NVD was found to down-regulate the JAK2/STAT3 signaling cascade, and reactivation of STAT3 diminished its anti-gastric cancer effects. Finally, the ingredient-target-disease network analysis also verified the anti-tumor effect of NVD.

This study highlights the potential of Nidus Vespae as a therapeutic agent for gastric cancer, providing insights into its molecular mechanisms of action.

The present study aimed to determine the potential of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), carbohydrate antigen (CA)19-9 and CA242 in predicting recurrence/metastasis of gastric cancer in patients following radical gastrectomy. The clinical data of 368 patients with stage I-III gastric cancer who underwent radical gastrectomy were analyzed, and CEA, AFP, CA19-9 and CA242 levels were detected prior to surgery and 6-12 months following surgery. Univariate and multivariate analyses were used to evaluate the potential risk factors for post-operative recurrence/metastasis of gastric cancer, and the predictive value of CEA, AFP, CA19-9 and CA242 levels was evaluated using receiver operating characteristic (ROC) curve and area under the curve (AUC). Cumulative survival rates were calculated using Kaplan-Meier analysis, and statistical significance was evaluated using a log-rank test. Results of the univariate analysis demonstrated that open surgery, age ≥70, total gastrectomy, disease stage III, and pre-operative CA19-9 and CA242 positivity were risk factors for recurrence/metastasis. ROC curve analysis revealed that the AUC values of postoperative CA19-9 were higher than other values. According to the Kaplan-Meier survival analysis, patients with negative CEA, AFP, CA19-9 and CA242 levels prior to surgery exhibited a higher five-year survival rate than those who exhibited positive levels of these tumor markers. In addition, patients with positive CEA, AFP, CA19-9 and CA242 levels prior to surgery exhibited a significantly worse prognosis. Collectively, the results of the present study indicated that CEA, AFP, CA19-9 and CA242 exhibited potential as predictive biomarkers for recurrence/metastasis following radical gastrectomy in patients with gastric cancer. Notably, CA19-9 and CA242 may exhibit the highest potential in predicting recurrence/metastasis.

Gastric cancer (GC) ranks fourth in global mortality rates and fifth in prevalence, making it one of the most common cancers worldwide. Recent clinical studies have highlighted the potential of immunotherapies as a promising approach to treating GC. This study aims to shed light on the most impactful therapeutic strategies in the context of GC immunotherapy, highlighting both established and emerging approaches.

This review examines over 160 clinical studies conducted globally, focusing on the effectiveness of various immunotherapy modalities, including cancer vaccines, adoptive cell therapy, immune checkpoint inhibitors (ICIs), and monoclonal antibodies (mAbs). A comprehensive search of peer-reviewed literature was performed using databases such as Web of Science, PubMed, and Scopus. The selection criteria included peer-reviewed articles published primarily within the last 10 years, with a focus on studies that provided insights into targeted therapies and their mechanisms of action, clinical efficacy, and safety profiles. The findings indicate that these immunotherapy strategies can enhance treatment outcomes for GC, aligning with current treatment guidelines. ICIs like pembrolizumab and nivolumab have shown significant survival benefits in specific GC subgroups. Cancer vaccines and CAR-T cell therapies demonstrate potential, while mAbs targeting HER2 and VEGFR pathways enhance outcomes in combination regimens. We discuss the latest advancements and challenges in targeted therapy and immunotherapy for GC. Given the evolving nature of this field, this research emphasizes significant evidence-based therapies and those currently under evaluation rather than providing an exhaustive overview. Challenges include resistance mechanisms, immunosuppressive tumor environments, and inconsistent results from combination therapies. Biomarker-driven approaches and further research into emerging modalities like CAR-T cells and cancer vaccines are critical for optimizing treatments.

Immunotherapy is reshaping GC management by improving survival and quality of life. Ongoing research and clinical evaluations are crucial for refining personalized and effective therapies.

Gastric cancer (GC) is a common malignant tumor of the digestive tract. Accumulating studies suggest that inflammation is linked with the pathogenesis of GC. The study delves into novel hematological inflammatory markers, such as systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and prognostic nutritional index (PNI), to explore their potential applications in early diagnosis of GC.

From October 2020 and August 2024, 1339 GC patients admitted to our hospital were enrolled in this study. The pre-treatment SII, SIRI, and PNI was calculated from peripheral blood samples. Univariate and multivariate logistic regression analyses were utilized to verify independent risk factors for patients, and constructed the nomograms. The correlation between hematological indicators and tumor-node-metastasis (TNM) stage was assessed through Spearman's analysis.

Eligible patients and healthy controls were grouped by gender. The diagnostic ability of PNI was significantly superior to other indicators to diagnose male GC (area under the curve [AUC]=0.908, 95% CI: 0.892-0.925) and female GC (AUC=0.890, 95% CI: 0.865-0.914). Besides, the combination of hematological indicators is more effective in diagnosing GC patients, especially for male patients (AUC=0.916, 95% CI: 0.901-0.932, sensitivity: 84.98%, specificity: 84.29%). The C-statistic of Nomogram model was 0.917 for males and 0.875 for females. In both male and female cohorts, CEA, SII, and SIRI were positively correlated with TNM stage, while PNI was negatively correlated. The AUC of CEA, SII, SIRI, and PNI combined for the diagnosis in the early stage of male GC patients was 0.897 (95% CI: 0.875-0.918, sensitivity: 86.57%, specificity: 80.30%) is higher than that of in the advanced stage (AUC: 0.745, 95% CI: 0.710-0.780, sensitivity: 56.53%, specificity: 82.86%).

The combined CEA, SII, PNI, and SIRI could be used as screening biomarkers in diagnosing GC, especially in the early stage of male GC patients.

The pro-tumor effects of mast cell (MC) in the tumor microenvironment (TME) are becoming increasingly clear. Recently, MC were shown to contribute to tumor malignancy by supporting the migration of tumor-associated macrophages (TAMs), suggesting a relationship with tumor immunity. In the current study, we aimed to examine the correlation between MC infiltration and neoadjuvant chemoradiotherapy (nCRT) response for locally advanced rectal cancer (LARC). Ninety-five LARC patients who recieved nCRT were enrolled in this study. Protein levels of the MC marker tryptase and TAM marker CD206 were evaluated with immunohistochemistry (IHC). The correlation between MC infiltration and prognostic factors was evaluated. The effects of MCs on the malignant potential were examined using in vitro proliferation and invasion assays with a colorectal cancer (CRC) cell line (HCT-116). Following nCRT, 31.6% of resected LARC patient specimens were positive for MC infiltration by tryptase IHC analysis. MC infiltration was significantly correlated with nCRT response. The 5-year disease-free survival (DFS) rate was significantly lower in the MC-positive group compared with the MC-negative group (52.3% vs. 76.8%). Univariate and multivariate analyses revealed that MC infiltration was the independent prognostic indicator for DFS. MC infiltration was significantly correlated with CD206 expression, and therefore TAMs. In vitro experiments suggested that tumor activated mast cells could promote CRC cell malignant behavior via production of macrophage inhibitory factor. MC infiltration in LARC patients was positively correlated with TAM infiltration and resistance to nCRT, and was also an independent poor prognostic indicator.

The scorpion Buthus martensii Karsch is edible and has been an essential resource in traditional Chinese medicine for treating numerous diseases. In this study, two small peptides from B. martensii hydrolysates were examined to elucidate their potential against gastric cancer. The small peptides (AK and GK) were identified using the LC-QTOF-MS-based approach. In silico prediction of therapeutic targets, MGC-803 cells and transgenic zebrafish models, and immunoblotting experiments were used to reveal the molecular mechanism of action of the peptides. The peptides AK and GK competitively bound to the receptor to modulate the TNF/TNFR-signaling cascade and alter the tumor microenvironment. EGFR, TP53, MYC, PTEN, and STAT3 were also identified as major functional targets of the peptides. Mechanistically, AK and GK inactivated the TNF-α/EGFR/STAT3-signaling pathway, decreased c-myc protein expression levels, and upregulated p53 and PTEN expression, thereby preventing TNF-α-induced tumor growth. Our findings indicated that AK and GK played a pivotal role in offsetting the inflammatory stimuli that caused gastric cancer cell invasion and highlighted the use of B. martensii resources as functional products with health benefits.

Gastric cancer (GC) is characterized by notable heterogeneity and the impact of molecular subtypes on treatment and prognosis. The role of programmed cell death (PCD) in cellular processes is critical, yet its specific function in GC is underexplored. This study applied multiomics approaches, integrating transcriptomic, epigenetic, and somatic mutation data, with consensus clustering algorithms to classify GC molecular subtypes and assess their biological and immunological features. A machine learning model was developed to create the Gastric Cancer Multi-Omics Programmed Cell Death Signature (GMPS), targeting PCD-related genes. We verified the expression of the GMPS hub genes using the RT-qPCR method. The prognostic influence of GMPS on GC was then evaluated. Single-cell analysis was performed to examine the heterogeneity of PCD characteristics in GC. Findings indicate that GMPS notably correlates with patient survival rates, tumor mutational burden (TMB), and copy number variations (CNV), demonstrating substantial prognostic predictive power. Moreover, GMPS is closely associated with the tumor microenvironment (TME) and immune therapy response. This research elucidates the molecular subtypes of GC, highlighting PCD's critical role in prognosis assessment. The relationship between GMPS and immune therapy response, alongside gastric cancer's microenvironmental features, provides insights for personalized treatment.

In addition to blood test data, inflammation-based prognostic markers have been used to predict the prognosis of various types of cancer. However, several of these previous studies may be outdated, as they were conducted prior to the widespread adoption of immune checkpoint inhibitors, leading to limited reports on their efficacy. The present study aimed to assess the accuracy of different inflammation-based prognostic markers in patients with advanced or recurrent gastric cancer undergoing nivolumab monotherapy as salvage-line chemotherapy. In a retrospective cohort study across Japan, a total of 159 patients with advanced or recurrent gastric cancer who were treated with nivolumab between September 2017 and March 2020 were selected. Blood test data were collected within 14 days of the start of chemotherapy and 17 inflammation-based prognostic markers were evaluated. Cox regression analysis was performed using all patient background factors. Subsequently, model selection was performed using backward elimination based on the Akaike information criterion (AIC) to obtain effective background factors which could be assessed for their impact on patient survival. For each marker, the magnitude of the impact on the survival rate, after adjusting for the background factors, was assessed using concordance and AIC analyses. A total of 159 patients (female, 30.2%; median age, 70 years) were included in the present study. Most patients received platinum, fluoropyrimidine and taxane treatment, with a median of three prior lines of systemic therapy. With a median follow-up of 3.3 months (95% CI, 2.5-3.8), median overall survival and time to treatment failure were 3.8 months (95% CI, 3.3-4.5) and 1.8 months (95% CI, 1.8-2.3), respectively. Amongst the 17 markers analyzed, the modified Glasgow prognostic score (mGPS) was classed as the most useful factor that affected the survival rate of patients. Real-world data showed that mGPS, an inflammation-based prognostic marker, had the strongest correlation with prognosis in patients with advanced or recurrent gastric cancer receiving nivolumab monotherapy. The present study was registered as a clinical trial with the UMIN Clinical Trial Registry (http://www.umin.ac.jp/ctr/index.htm) under the trial registration number UMIN000050590 on 15th March 2023.

Esophageal carcinoma (EC) is one of the most common tumors in China and seriously affects patient survival and quality of life. In recent years, increasing studies have shown that the tumor microenvironment is crucial in promoting tumor progression and metastasis. Tumor-associated macrophages (TAM) are key components of the tumor immune microenvironment and promote both tumor growth and antitumor immunity. Much evidence suggests that TAMs are closely associated with esophageal tumors. However, understanding of the clinical value and mechanism of action of TAM in esophageal cancer remains limited. Therefore, we reviewed the status of research on the role and mechanism of action of TAM in EC progression and summarized its potential clinical application value to provide a theoretical basis for the clinical treatment of EC.

In recent studies, accumulating evidence has revealed a strong association between the inflammatory response and the prognosis of many tumors. There is a certain correlation of neutrophil-to-lymphocyte ratio (NLR) with the prognosis in gastric cancer (GC) patients undergoing neoadjuvant chemotherapy (NAC). However, the existing research results have remained controversial.

To explore the relationship between NLR ratio and prognosis of GC patients receiving NAC.

A thorough systematic search was performed in databases such as PubMed, Embase, Web of Science, and Cochrane Library, the search is available until February 29, 2024, and studies exploring the interaction of NLR with clinical outcomes were collected. Relevant studies meeting pre-defined inclusion and exclusion criteria were carefully chosen. The outcomes included progression-free survival (PFS), relapse-free survival, disease-free survival (DFS), and overall survival (OS). The hazard ratio (HR) and its corresponding 95% confidence interval (CI) were utilized for estimation.

Our analysis encompassed 852 patients and incorporated data from 12 cohort studies. The comprehensive analysis revealed a significant association of high NLR with reduced OS (HR = 1.76; 95%CI: 1.22-2.54, P = 0.003), relapse-free survival (HR = 3.73; 95%CI: 1.74-7.96, P = 0.0007), and PFS (HR = 2.32; 95%CI: 1.42-3.81, P = 0.0008) in patients. However, this correlation in disease-free survival was not significant. NLR demonstrated its crucial role in effectively predicting the OS of GC patients undergoing NAC at different detection times, ages, regions, and NLR thresholds.

In GC patients receiving NAC, an elevated NLR is strongly associated with reduced OS and PFS. NLR has become an effective biomarker for patient prognosis evaluation, providing valuable insights for the treatment strategies of NAC in GC patients.

Cardia gastric cancer (CGC) is prevalent in East Asia, and noninvasive, cost-effective screening methods are needed. This study investigated the diagnostic value of serum pepsinogen (PG), gastrin-17 (G-17), Helicobacter pylori (H. pylori) antibodies, and proteomic profiling for CGC and precancerous lesions. We conducted a case-control study involving biopsy-confirmed patients with CGC (n = 60), low-grade intraepithelial neoplasia (CLGD, n = 60), high-grade intraepithelial neoplasia (CHGD, n = 64), and healthy controls (n = 120) matched for age and sex from high-incidence areas in China. Serological markers including PGI, PGII, G-17, and H. pylori were measured using ELISA and Western blot, while plasma protein markers were assessed using Olink® technology. The VSOLassoBag algorithm and nine machine learning (ML) algorithms were employed to identify crucial features and construct predictive models. Various evaluation metrics, including the area under the receiver-operating-characteristic curve (AUC), were utilized to compare predictive performance. Elevated PGII levels, decreased PGR, and H. pylori infection were significantly associated with an increased risk of CGC and precancerous lesions (P for trend < 0.05). The eXtreme Gradient Boosting (XGBoost) model performed best in discriminative ability among the 9 ML models. Following feature reduction based on predictive performance, a final explainable XGBoost model was developed, incorporating five protein biomarkers (CDHR2, ICAM4, PTPRM, CDC27, and FLT1). This model exhibited excellent performance in distinguishing individuals with CGC and precancerous lesions from healthy controls (AUC = 0.931 for CGC, 0.867 for CHGD, and 0.763 for CLGD), surpassing the traditional serological marker-based model. This study underscores the diagnostic potential of serological markers and proteomic profiling in the detection of CGC. Further validation and exploration of combined biomarker approaches are warranted to enhance early diagnosis and improve outcomes in high-risk populations.

Treatment options for intrahepatic cholangiocarcinoma (iCCA), a highly malignant tumor with poor prognosis, are limited. Recent developments in immunotherapy and immune checkpoint inhibitors (ICIs) have offered new hope for treating iCCA. However, several issues remain, including the identification of reliable biomarkers of response to ICIs and immune-based combinations. Tumor immune microenvironment (TIME) of these hepatobiliary tumors has been evaluated and is under assessment in this setting in order to boost the efficacy of ICIs and to convert these immunologically "cold" tumors to "hot" tumors. Herein, the review TIME of ICCA and its critical function in immunotherapy. Moreover, this paper also discusses potential avenues for future research, including novel targets for immunotherapy and emerging treatment plans aimed to increase the effectiveness of immunotherapy and survival rates for iCCA patients.

Immune checkpoint inhibitors (ICIs) have shown encouraging treatment efficacy for upper gastrointestinal cancers (UGICs). However, durable clinical responses only existed in a minority of patients. We evaluated evidence predicting survival benefits to identify the optimal population followed by ICI-based therapy.

A comprehensive search was performed using PubMed, Embase, Cochrane Library, and Web of Science to identify clinical trials for UGICs with ICI-based therapy. The outcomes were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation System (GRADE).

Thirty-six studies comprising 12,440 patients were included for quantitative synthesis. Patients with PD-L1-positive (OR = 2.08, p < 0.00001), EBV+ (OR = 8.47, p = 0.003) tumors were more likely to respond to ICI treatment. Moreover, OS was significantly improved with the statistical subgroup difference concerning sex (p = 0.02) and region (p = 0.02). An exploratory subgroup analysis showed significantly improved OS with ICI plus chemotherapy in patients with CPS ≥ 10 (HR = 0.66, p = 0.001) and CPS ≥ 1 (HR = 0.75, p < 0.00001).

UGIC patients with PD-L1-positive, EBV + status are associated with a better therapeutic response to ICI-based therapy. The male patients and Asian patients could derive more survival benefits following ICI treatment than female and non-Asian ones. A combination of prognostic and predictive factors was suggested to help guide immunotherapy decision-making in UGIC patients.

The tumor microenvironment (TME) is a critical determinant in the initiation, progression, and treatment outcomes of various cancers. Comprising of cancer-associated fibroblasts (CAF), immune cells, blood vessels, and signaling molecules, the TME is often likened to the soil supporting the seed (tumor). Among its constituents, tumor-associated macrophages (TAMs) play a pivotal role, exhibiting a dual nature as both promoters and inhibitors of tumor growth. This review explores the intricate relationship between TAMs and the TME, emphasizing their diverse functions, from phagocytosis and tissue repair to modulating immune responses. The plasticity of TAMs is highlighted, showcasing their ability to adopt either protumorigenic or anti-tumorigenic phenotypes based on environmental cues. In the context of cancer, TAMs' pro-tumorigenic activities include promoting angiogenesis, inhibiting immune responses, and fostering metastasis. The manuscript delves into therapeutic strategies targeting TAMs, emphasizing the challenges faced in depleting or inhibiting TAMs due to their multifaceted roles. The focus shifts towards reprogramming TAMs to an anti-tumorigenic M1-like phenotype, exploring interventions such as interferons, immune checkpoint inhibitors, and small molecule modulators. Noteworthy advancements include the use of CSF1R inhibitors, CD40 agonists, and CD47 blockade, demonstrating promising results in preclinical and clinical settings. A significant section is dedicated to Chimeric Antigen Receptor (CAR) technology in macrophages (CAR-M cells). While CAR-T cells have shown success in hematological malignancies, their efficacy in solid tumors has been limited. CAR-M cells, engineered to infiltrate solid tumors, are presented as a potential breakthrough, with a focus on their development, challenges, and promising outcomes. The manuscript concludes with the exploration of third-generation CAR-M technology, offering insight into in-vivo reprogramming and nonviral vector approaches. In conclusion, understanding the complex and dynamic role of TAMs in cancer is crucial for developing effective therapeutic strategies. While early-stage TAM-targeted therapies show promise, further extensive research and larger clinical trials are warranted to optimize their targeting and improve overall cancer treatment outcomes.

The neural differentiation of dental pulp stem cells (DPSCs) exhibits great potential in the treatment of dental pulp repair and neurodegenerative diseases. However, the precise molecular mechanisms underlying this process remain unclear. This study was designed to reveal the roles and regulatory mechanisms of the armadillo repeat-containing X-linked 3 (ARMCX3) in neural differentiation and inflammatory microenvironment in human DPSCs (hDPSCs).

We treated hDPSCs with porphyromonas gingivalis lipopolysaccharide (Pg-LPS) to simulate the inflammatory microenvironment. Then the lentiviral vectors were introduced to construct stable cell lines with ARMCX3 knockdown or overexpression. The expression of neural-specific markers, ARMCX3 and inflammation factors were estimated by immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) assays. Additionally, we used IF assays and specific kits to investigate the regulatory role of ARMCX3 on reactive oxygen species (ROS) signaling. Moreover, a ROS inhibitor was utilized to verify whether ROS inhibition reversed the effects of ARMCX3 in Pg-LPS-treated hDPSCs.

This work illustrated that Pg-LPS treatment significantly enhanced ARMCX3 expression and inflammatory response, and inhibited neural differentiation in hDPSCs. ARMCX3 knockdown effectively accelerated neural differentiation and controlled inflammatory cytokines at a lower level in hDPSCs in the presence of Pg-LPS. Additionally, knockdown of ARMCX3 notably reduced ROS production and ROS inhibition effectively eliminated the roles of ARMCX3 overexpression in hDPSCs. Besides, all results were proved to be statistically significant.

This investigation proved that ARMCX3 affected neural differentiation and inflammation microenvironment in hDPSCs at least partly by mediating ROS signal. These findings provided a new perspective on the mechanism of neural differentiation of hDPSCs and help to better explore the therapeutic schedule of pulpitis and neurodegenerative diseases.

Diabetes induces a range of macrovascular and microvascular changes, which lead to significant clinical complications. Although many studies have tried to solve the diabetic problem using drugs, it remains unclear. In this study, we investigated whether resistance exercise affects cardiovascular factors and inflammatory markers in diabetes. The study subjected Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have genetically induced diabetes mellitus, to a resistance exercise program for 12 weeks and assessed the levels of cardiovascular factors and inflammatory markers using western blotting analysis, ELISA, and immunohistochemistry. During the training period, OLETF + exercise (EX) group exhibited lower body weight and reduced glucose levels when compared with OLETF group. Western blotting analysis, ELISA, and immunohistochemistry revealed that the levels of PAI-1, VACM-1, ICAM-1, E-selectin, TGF-β, CRP, IL-6, and TNF-α were decreased in OLETF + EX group when compared with the OLETF group. Moreover, the anti-inflammatory markers, IL-4 and IL-10, were highly expressed after exercise. Therefore, these results indicate that exercise may influence the regulation of cardiovascular factors and inflammatory markers, as well as help patients with metabolic syndromes regulate inflammation and cardiovascular function.

Multiplexed immunofluorescence (mIF) staining, such as CODEX and MIBI, holds significant clinical value for various fields, such as disease diagnosis, biological research, and drug development. However, these techniques are often hindered by high time and cost requirements.

Here we present a Multimodal-Attention-based virtual mIF Staining (MAS) system that utilises a deep learning model to extract potential antibody-related features from dual-modal non-antibody-stained fluorescence imaging, specifically autofluorescence (AF) and DAPI imaging. The MAS system simultaneously generates predictions of mIF with multiple survival-associated biomarkers in gastric cancer using self- and multi-attention learning mechanisms.

Experimental results with 180 pathological slides from 94 patients with gastric cancer demonstrate the efficiency and consistent performance of the MAS system in both cancer and noncancer gastric tissues. Furthermore, we showcase the prognostic accuracy of the virtual mIF images of seven gastric cancer related biomarkers, including CD3, CD20, FOXP3, PD1, CD8, CD163, and PD-L1, which is comparable to those obtained from the standard mIF staining.

The MAS system rapidly generates reliable multiplexed staining, greatly reducing the cost of mIF and improving clinical workflow.

Stanford 2022 HAI Seed Grant; National Institutes of Health 1R01CA256890.

Cancer immunotherapy aims to unleash the immune system's potential against cancer cells, providing sustained relief for tumors responsive to immune checkpoint inhibitors (ICIs). While promising in gastric cancer (GC) trials, the efficacy of ICIs diminishes in the context of peritoneal dissemination. Our objective is to identify strategies to enhance the impact of ICI treatment specifically for cases involving peritoneal dissemination in GC.

The therapeutic efficacy of anti-PD1, CTLA4 treatment alone, or in combination was assessed using the YTN16 peritoneal dissemination tumor model. Peritoneum and peritoneal exudate cells were collected for subsequent analysis. Immunohistochemical staining, flow cytometry, and bulk RNA-sequence analyses were conducted to evaluate the tumor microenvironment (TME). A Janus kinase inhibitor (JAKi) was introduced based on the pathway analysis results.

Anti-PD1 and anti-CTLA4 combination treatment (dual ICI treatment) demonstrated therapeutic efficacy in certain mice, primarily mediated by CD8 + T cells. However, in mice resistant to dual ICI treatment, even with CD8 + T cell infiltration, most of the T cells exhibited an exhaustion phenotype. Notably, resistant tumors displayed abnormal activation of the Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway compared to the untreated group, with observed infiltration of macrophages, neutrophils, and Tregs in the TME. The concurrent administration of JAKi rescued CD8 + T cells function and reshaped the immunosuppressive TME, resulting in enhanced efficacy of the dual ICI treatment.

Dual ICI treatment exerts its anti-tumor effects by increasing tumor-specific CD8 + T cell infiltration, and the addition of JAKi further improves ICI resistance by reshaping the immunosuppressive TME.

Pancreatic cancer (PC) is one of the deadliest cancers worldwide with low survival rates and poor outcomes. The treatment landscape for PC is fraught with obstacles, including drug resistance, lack of effective targeted therapies and the immunosuppressive tumor microenvironment (TME). The resistance of PC to existing immunotherapies highlights the need for innovative approaches, with the TME emerging as a promising therapeutic target. The recent advancements in understanding the role of macrophages, this context highlight their significant impact on tumor development and progression. There are two important types of macrophages: M1 and M2, which play critical roles in the TME. Therapeutics strategies including, depletion of tumor-associated macrophages (TAMs), reprogramming TAMs to promote anti-tumor activity, and targeting macrophage recruitment can lead to promising outcomes. Targeting macrophage-related pathways may offer novel strategies for modulating immune responses, inhibiting angiogenesis, and overcoming resistance to chemotherapy in PC treatment.

M2-like tumor-associated macrophages (M2-like TAMs) play key roles in tumor progression and the immune response. However, the clinical significance and prognostic value of M2-like TAMs-associated regulatory genes in gastric cancer (GC) have not been clarified.

Herein, we identified M2-like TAM-related genes by weighted gene coexpression network analysis of TCGA-STAD and GSE84437 cohort. Lasso-Cox regression analyses were then performed to screen for signature genes, and a novel signature was constructed to quantify the risk score for each patient. Tumor mutation burden (TMB), survival outcomes, immune cells, and immune function were analyzed in the risk groups to further reveal the immune status of GC patients. A gene-drug correlation analysis and sensitivity analysis of anticancer drugs were used to identify potential therapeutic agents. Finally, we verified the mRNA expression of signature genes in patient tissues by qRT-PCR, and analyzed the expression distribution of these genes by IHC.

A 4-gene (SERPINE1, MATN3, CD36, and CNTN1) signature was developed and validated, and the risk score was shown to be an independent prognostic factor for GC patients. Further analyses revealed that GC patients in the high-risk group had a worse prognosis than those in the low-risk group, with significant differences in TMB, clinical features, enriched pathways, TIDE score, and tumor microenvironment features. Finally, we used qRT-PCR and IHC analysis to verify mRNA and protein level expression of signature genes.

These findings highlight the importance of M2-like TAMs, provide a new perspective on individualized immunotherapy for GC patients.

The prognosis nutritional index (PNI) and the systemic inflammatory immunological index (SII) are characteristic indicators of the nutritional state and the systemic inflammatory response, respectively. However, there is an unknown combined effect of these indicators in the clinic. Therefore, the practicality of using the SII-PNI score to predict prognosis and tumor response of locally advanced gastric cancer (LAGC) following chemotherapy was the main focus of this investigation.

We retrospectively analyzed 181 patients with LAGC who underwent curative resection after neoadjuvant chemotherapy in a prospective study (NCT01516944). We divided these patients into tumour regression grade(TRG) 3 and non-TRG3 groups based on tumor response (AJCC/CAP guidelines). The SII and PNI were assessed and confirmed the cut-off values before treatment. The SII-PNI values varied from 0 to 2, with 2 being the high SII (≥ 471.5) as well as low PNI (≤ 48.6), a high SII or low PNI is represented by a 1 and neither is represented by a 0, respectively.

51 and 130 samples had TRG3 and non-TRG3 tumor responses respectively. Patients with TRG3 had substantially higher SII-PNI scores than those without TRG3 (p < 0.0001). Patients with greater SII-PNI scores had a poorer prognosis (p < 0.0001). The SII-PNI score was found to be an independent predictor of both overall survival (HR = 4.982, 95%CI: 1.890-10.234, p = 0.001) and disease-free survival (HR = 4.763, 95%CI: 1.994-13.903, p = 0.001) in a multivariate analysis.

The clinical potential and accuracy of low-cost stratification based on SII-PNI score in forecasting tumor response and prognosis in LAGC is satisfactory.

This retrospective study analyzed a large population of gastric cancer (GC) patients treated between 2010 and 2015 to investigate the clinical features and predictive risk factors for developing secondary primary malignancies (SPMs). The cumulative incidence of SPM was assessed using Kaplan-Meier analysis. Competing risk analyses adjusted for mortality were conducted using stratified Cox proportional hazard regression models and multivariate analyses to identify independent predictors of SPM. A total of 3289 out of 167,747 GC patients were included in the analytic cohort, with 155 patients diagnosed with SPM. Patients whose histologic type other than adenocarcinomas (AC) and signet ring cell carcinoma (SRCC) emerged as an independent risk factor for developing SPM (hazard ratio [HR] 2.262, 95% confidence interval [CI] 1.146-4.465, P = 0.019) in multivariate Cox regression analysis. The surgical method, including biopsy/local excision (HR 2.3, [CI] 1.291-4.095, P = 0.005) and subtotal/total resection ([HR] 1.947, [CI] 1.028-3.687, P = 0.041), chemotherapy ([HR] 1.527, [CI] 1.006-2.316, P = 0.047), and histologic type ([HR] 2.318, [CI] 1.193-4.504, P = 0.013)), were identified as independent risk factors in the competitive risk model. Subgroup analyses, stratified by chemotherapy, revealed an increased risk of SPM among older patients. Furthermore, a nomogram was developed and internally validated to predict the cumulative incidence of SPM in GC patients (C-index = 0.73 for 72 months). These findings suggested that in specific histologic types of GC, the lymph node infiltration region missed after local surgical resection, and concomitant chemotherapy would have an increased risk of SPM for cancer survivors.

Gastric adenocarcinoma harbors a range of genetic and epigenetic alterations, including alterations in DNA copy number. However, the key genes that promote the development and progression of gastric adenocarcinoma remain unknown. To identify the key genes amplified in gastric adenocarcinoma, we performed array comparative genomic hybridization on formalin-fixed paraffin-embedded samples of surgically resected gastric adenocarcinoma. We detected a relatively wide genomic region of gain containing the vascular endothelial growth factor A (VEGFA) gene locus on chromosome 6p. VEGFA locus amplification in gastric adenocarcinoma was validated by fluorescence in situ hybridization. To assess the frequency of VEGFA locus amplification in gastric adenocarcinoma, we conducted multiplex ligation-dependent probe amplification (MLPA) assays using homemade probes designed to target the VEGFA gene locus. Eleven of 54 (20 %) gastric adenocarcinomas with MLPA values above 1.3 were defined as having VEGFA locus amplification. Next, we investigated the effect of VEGFA locus amplification on the clinicopathological characteristics of gastric adenocarcinomas and patient survival. VEGFA locus amplification demonstrated a significantly close relationship with pathological intestinal type and lower rates of venous invasion Furthermore, a Kaplan-Meier analysis showed that patients with VEGFA locus amplification had significantly better overall survival than those without amplification (p = 0.038), particularly in the long-term follow-up period. In conclusion, VEGFA locus amplification can predict modest aggressiveness and good outcomes, suggesting the possibility that it may predict a favorable prognosis in patients with gastric adenocarcinoma.

Tumor-associated macrophages (TAMs) represent one of the most abundant tumor-infiltrating stromal cells, and their normal function in tumor microenvironment (TME) is to suppress tumor cells by producing cytokines which trigger both direct cell cytotoxicity and antibody-mediated immune response. However, upon prolonged exposure to TME, the classical function of these so-called M1-type TAMs can be converted to another type, "M2-type," which are recruited by tumor cells so that they promote tumor growth and metastasis. This is the reason why the accumulation of TAMs in TME is correlated with poor prognosis in cancer patients. Both M1- and M2-types have high degree of plasticity, and M2-type cells can be reprogrammed to M1-type for therapeutic purposes. This characteristic introduces TAMs as promising target for developing novel cancer treatments. In addition, inhibition of M2-type cells and blocking their recruitment in TME, as well as their depletion by inducing apoptosis, are other approaches for effective immunotherapy of cancer. In this review, we summarize the potential of TAMs to be targeted for cancer immunotherapy and provide an up-to-date about novel strategies for targeting TAMs.

Gastric cancer (GC) is a malignant tumor originating from the gastric mucosa epithelium, and there is a low survival rate of GC patients after treatment, with a poor prognostic outcome. The inflammatory response within the tumor microenvironment plays an important role in GC progression.

We downloaded GC-related datasets and inflammation-related genes from GEO, TCGA and MSigDB databases, performed differential analysis, protein-protein interaction analysis, immunoinfiltration analysis and Lasso analysis to screen inflammation-related hub genes affecting GC progression, and carried out qRT-PCR for validation. In order to explore the role of ADH1A, we constructed overexpressed plasmids, treated GC cells with cGMP/PKG pathway agonist 8-Br-cGMP, and tested cell functions with CCK8, EdU, Transwell, scratch assay and other experiments. On this basis, GC cells were co-cultured with monocyte THP-1 to explore the effect of ADH1A on the polarization of macrophages.

ADH1A was significantly decreased in GC cells, and its expression trend was consistent with the results of bioinformatics analysis. Therefore, we chose ADH1A for subsequent functional validation. Overexpression of ADH1A in GC cells revealed ADH1A's role in inhibiting the activity, proliferation, migration and invasion of GC cells, promoting apoptosis and secretion of IL-6, IFN-γ, CCL5 and CSF2, and facilitating the transformation of macrophages to a pro-inflammatory M1 phenotype. ssGSEA results demonstrated the potential involvement of ADH1A in the cGMP/PKG signaling pathway, and significant changes in the expression of proteins related to the cGMP/PKG signaling pathway. The use of the cGMP/PKG signaling pathway agonist 8-Br-cGMP in ADH1A-overexpressing GC cells substantiated ADH1A's capacity to inhibit the cGMP/PKG signaling pathway, thereby suppressing the malignant progression of GC and promoting the transformation of macrophages to a pro-inflammatory M1 phenotype.

ADH1A is able to influence the malignant progression of GC and the transformation of macrophages to the pro-inflammatory M1 phenotype through the cGMP/PKG signaling pathway.

Prostate cancer represents the second most prevalent form of cancer found in males, and stands as the fifth primary contributor to cancer-induced mortality on a global scale. Research has shown that transplanted mesenchymal stem cells (MSCs) can migrate by homing to tumor sites in the body. In prostate cancer, researchers have explored the fact that MSC-based therapies (including genetically modified delivery vehicles or vectors) and MSC-derived exosomes are emerging as attractive options to improve the efficacy and safety of traditional cancer therapies. In addition, researchers have reported new insights into the application of extracellular vesicle (EV)-MSC therapy as a novel treatment option that could provide a more effective and targeted approach to prostate cancer treatment. Moreover, the new generation of exosomes, which contain biologically functional molecules as signal transducers between cells, can simultaneously deliver different therapeutic agents and induce an anti-tumor phenotype in immune cells and their recruitment to the tumor site. The results of the current research on the use of MSCs in the treatment of prostate cancer may be helpful to researchers and clinicians working in this field. Nevertheless, it is crucial to emphasize that although dual-role MSCs show promise as a therapeutic modality for managing prostate cancer, further investigation is imperative to comprehensively grasp their safety and effectiveness. Ongoing clinical trials are being conducted to assess the viability of MSCs in the management of prostate cancer. The results of these trials will help determine the viability of this approach. Based on the current literature, engineered MSCs-EV offer great potential for application in targeted tumor therapy.

Inflammatory factors have increasingly become a more cost-effective prognostic indicator for gastric cancer (GC). The goal of this study was to develop a prognostic score system for gastric cancer patients based on inflammatory indicators.

Patients' baseline characteristics and anthropometric measures were used as predictors, and independently screened by multiple machine learning(ML) algorithms. We constructed risk scores to predict overall survival in the training cohort and tested risk scores in the validation. The predictors selected by the model were used in multivariate Cox regression analysis and developed a nomogram to predict the individual survival of GC patients.

A 13-variable adaptive boost machine (ADA) model mainly comprising tumor stage and inflammation indices was selected in a wide variety of machine learning models. The ADA model performed well in predicting survival in the validation set (AUC = 0.751; 95% CI: 0.698, 0.803). Patients in the study were split into two sets - "high-risk" and "low-risk" based on 0.42, the cut-off value of the risk score. We plotted the survival curves using Kaplan-Meier analysis.

The proposed model performed well in predicting the prognosis of GC patients and could help clinicians apply management strategies for better prognostic outcomes for patients.

This study aimed to develop and validate a clinical and imaging-based nomogram for preoperatively predicting perineural invasion (PNI) in advanced gastric cancer.

A retrospective cohort of 351 patients with advanced gastric cancer who underwent surgical resection was included. Multivariable logistic regression analysis was conducted to identify independent risk factors for PNI and to construct the nomogram. The performance of the nomogram was assessed using calibration curves, the concordance index (C-index), the area under the curve (AUC), and decision curve analysis (DCA). The disparity in disease-free survival (DFS) between the nomogram-predicted PNI-positive group and the nomogram-predicted PNI-negative group was evaluated using the Log-Rank test and Kaplan-Meier analysis.

Extramural vascular invasion (EMVI), Borrmann classification, tumor thickness, and the systemic inflammation response index (SIRI) emerged as independent risk factors for PNI. The nomogram model demonstrated a commendable AUC value of 0.838. Calibration curves exhibited excellent concordance, with a C-index of 0.814. DCA indicated that the model provided good clinical net benefit. The DFS of the nomogram-predicted PNI-positive group was significantly lower than that of the nomogram-predicted PNI-negative group (p < 0.001).

This study successfully developed a preoperative nomogram model that not only effectively predicted PNI in gastric cancer but also facilitated postoperative risk stratification.

Head and neck cancer is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, being one of the leading causes of cancer morbidity and mortality worldwide. CC Chemokine receptor 7(CCR7) is a multifunctional G protein-coupled trans-membrane chemokine that affects immune cell chemotaxis, migration, and cancer progression through its interaction with its ligands C-C motif chemokine ligand 19(CCL19) and C-C motif chemokine ligand 21(CCL21). Numerous studies have demonstrated the involvement of CCR7 in the malignant progression of a variety of cancers, reflecting the pro-cancer properties of CCR7. The Cancer Genome Atlas data suggests CCR7 has elevated expression in oral cancer. Specifically, CCR7 expression in tumor microenvironment (TME) may regulate the ability of some immune cells to engage in anti-tumor immune responses. Since CD8+ T cells have become a key immunotherapeutic target, the role of CCR7 in antitumor immune response of naïve CD8+ T cells in TME has not been thoroughly investigated.

A CCR7 knockout mouse model was constructed, and the mechanism of ccr7 on the regulation of tumor microenvironment by naïve CD8+ T cells was verified under the guidance of single-cell RNA sequencing combined with in vivo animal experiments and in vitro cell experiments.

CCR7 is knocked out with impaired tumor growth and altered CD8+ T cell profiles, revealing the importance of this protein in OSCC.

Inhibition of CCR7 enhances CD8+ T cell activation, proliferation, and anti-tumor function, suggesting its potential as a therapeutic target.

Gastric cancer (GC), considered the fifth most prevalent malignancy, is the fourth leading cause of cancer death worldwide. This cancer is heterogeneous and invasive and often metastasizes to the liver. The survival of patients with GC, especially cancer-specific survival (CSS), is a matter of concern to their families and medical workers in clinical practice. However, efficient tools for early risk prediction are lacking. Thus, this study aimed to develop a nomogram for forecasting the overall survival (OS) and CSS of patients with GC with liver metastasis (GCLM) based on the Surveillance, Epidemiology, and End Results (SEER) database.

Information on individuals with GCLM was acquired from the SEER database from January 2000 to December 2015. Patients' data were randomized into the train cohort and the test cohort. The independent factors for CSS and OS were determined by univariate and multivariate competing risk analyses and Cox proportional hazards analysis, and the nomograms for predicting CSS and OS were constructed. The receiver operating characteristic curve and calibration curve were used to measure the accuracy and calibration of nomograms.

Our study included 4372 patients with GCLM, with 3060 patients in the train set and 1312 in the test set. The mean follow-up period was 12.31 months. The independent factors influencing the OS of patients with GCLM were age, bone metastasis, chemotherapy, grade, lung metastasis, stage, primary site, radiotherapy, surgical primary site, T stage, and tumor size. The concordance Index (C-index) of the constructed nomogram for OS were 0.718 (SE, 0.004) in the train set and 0.0.680 (SE, 0.006) in the test set. The independent factors affecting the CSS of patients with GCLM were age, chemotherapy, grade, lung metastasis, stage, radiotherapy, regional lymph node positive, surgical primary site, and total number of tumors. The C-index for the constructed nomogram for CSS were 0.696 (SE, 0.005) in the train set and 0.696 (SE, 0.008) in the test set.

The constructed nomograms showed satisfactory performance in predicting the OS and CSS of patients with GCLM, which can help clinicians formulate follow-up and rehabilitation strategies conducive to survival. At the same time, it can provide more family and social support for high-risk groups.

The main component of O-glycoproteins, mucin, is known to play important roles in physiological conditions and oncogenic processes, particularly correlated with poor prognosis in different carcinomas. Diffuse-type gastric cancer (DGC) has long been associated with genomic stability and unfavorable clinical outcomes. To investigate further, we obtained clinical information and the RNA-seq data of the TCGA-STAD cohort. Through the use of unsupervised clustering methods and GSEA, we identified two distinct clusters, characterized by higher and lower expression of MUC2 and MUC20, denoted as cluster 1 and cluster 2, respectively. Subsequently, employing CIBERSORT, it was determined that cluster 2 exhibited a higher tumor mutation burden (TMB) and a greater abundance of CD8+ T cells and activated CD4+ memory T cells, in addition to immune checkpoints (ICPs). On the other hand, cluster 1 showed a lower TIDE score estimation, indicating a higher probability of tumor immune escape. Furthermore, overexpression of MUC15 and MUC20 was confirmed through qPCR and Western blotting, and their specific roles in mediating the epithelial-mesenchymal transition (EMT) process of GC cells (SNU484 and Hs746t) were validated via CCK-8 assay and wound healing assay in vitro. These findings highlight the potential prognostic value of MUC20 and offer insights into the prospects of immunotherapy for DGC by targeting MUC20.

Treatment options for T3N1 stage gastric cancer exhibit regional variation, with optimal approach remaining unclear. We derived our data from the SEER database, using Cox proportional risk regression models for univariate and multivariate analyses of 5-years overall survival (5yOS) and 5-years cancer-specific survival (5yCSS). The results showed that younger age, female, non-white race, highly differentiated histologic grade, non-Signet ring cell adenocarcinoma, low N stage, lesser curvature of the stomach, OP followed by adjuvant C/T with or without RT, partial gastrectomy, C/T and others, Radiation therapy, and Chemotherapy were significantly associated with better 5yOS and 5yCSS. For patients with stage T3N1-3 gastric cancer, multimodal treatment regimens demonstrate superior survival outcomes compared to surgery or radiotherapy alone. Among them, OP followed by adjuvant C/T with or without RT emerges as particularly efficacious, potentially offering enhanced benefits for non-Asian populations.

Tumour-associated macrophages (TAMs), encompassing M1 and M2 subtypes, exert significant effects on osteosarcoma (OS) progression and immunosuppression. However, the impacts of TAM-derived biomarkers on the progression of OS remains limited. The GSE162454 profile was subjected to single-cell RNA (scRNA) sequencing analysis to identify crucial mediators between TAMs and OS cells. The clinical features, effects and mechanisms of these mediators on OS cells and tumour microenvironment were evaluated via biological function experiments and molecular biology experiments. Phosphodiesterase 4C (PDE4C) was identified as a pivotal mediator in the communication between M2 macrophages and OS cells. Elevated levels of PDE4C were detected in OS tissues, concomitant with M2 macrophage level, unfavourable prognosis and metastasis. The expression of PDE4C was observed to increase during the conversion process of THP-1 cells to M2 macrophages, which transferred the PDE4C mRNA to OS cells through exosome approach. PDE4C increased OS cell proliferation and mobility via upregulating the expression of collagens. Furthermore, a positive correlation was observed between elevated levels of PDE4C and increased TIDE score, decreased response rate following immune checkpoint therapy, reduced TMB and diminished PDL1 expression. Collectively, PDE4C derived from M2 macrophages has the potential to enhance the proliferation and mobility of OS cells by augmenting collagen expression. PDE4C may serve as a valuable biomarker for prognosticating patient outcomes and response rates following immunotherapy.

Tumor growth induces the tumor margin to become a transition zone rich in immune cells. EVPL is a potential prognostic biomarker for melanoma. Melanoma is difficult to cure because of its high metastasis, so it is urgent to find effective genes to inhibit tumor progression and regulate tumor microenvironment.

Firstly, differentially expressed genes (DEGs) among normal skin, nevus and melanoma samples in GSE3189 were screened. Bioinformatics was used to further explore the hub genes and enriched pathways closely related to the inflammatory response of DEGs in melanoma. We selected EVPL, which is associated with the Ras/Raf signaling pathway, for in vitro study. CCK-8, colony formation, wound healing, Transwell and flow cytometry assays were respectively used to evaluate the proliferation, migration, invasion, and apoptosis of cancer cells. Enzyme-linked immunosorbent assay was conducted for the monitoring of changes in the tumor microenvironment. To evaluate the effect of EVPL on macrophage recruitment, we established a co-culture system in a Transwell chamber. The polarization of macrophages was examined after treatment of cells with RAS/ERK signaling inhibitors SCH772984 and sh-EVPL. Additionally, changes in the expression of pathway proteins were measured by Western blot.

Among the screened hub genes, EVPL was associated with the Ras/Raf pathway, a key signaling pathway in melanoma, and may be involved in regulating the inflammatory microenvironment of melanoma. Oe-EVPL was proved to suppress melanoma cell malignant progression. By inhibiting EVPL expression, the inhibitory effects on melanoma progression induced by the addition of SCH772984 were reversed. Furthermore, EVPL was found to inhibit the expression of chemokines, the recruitment of macrophages, and the polarization of macrophages through the Ras/Raf/ERK signaling pathway.

EVPL can inhibit the progression of melanoma through the RAS/ERK signaling pathway, change the inflammatory tumor microenvironment of melanoma, and inhibit the recruitment of macrophages.

Gastric cancer (GC) is a highly aggressive malignancy with a heterogeneous nature, which makes prognosis prediction and treatment determination difficult. Inflammation is now recognized as one of the hallmarks of cancer and plays an important role in the aetiology and continued growth of tumours. Inflammation also affects the prognosis of GC patients. Recent reports suggest that a number of inflammatory-related biomarkers are useful for predicting tumour prognosis. However, the importance of inflammatory-related biomarkers in predicting the prognosis of GC patients is still unclear.

To investigate inflammatory-related biomarkers in predicting the prognosis of GC patients.

In this study, the mRNA expression profiles and corresponding clinical information of GC patients were obtained from the Gene Expression Omnibus (GEO) database (GSE66229). An inflammatory-related gene prognostic signature model was constructed using the least absolute shrinkage and selection operator Cox regression model based on the GEO database. GC patients from the GSE26253 cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent prognostic factors, and a prognostic nomogram was established. The calibration curve and the area under the curve based on receiver operating characteristic analysis were utilized to evaluate the predictive value of the nomogram. The decision curve analysis results were plotted to quantify and assess the clinical value of the nomogram. Gene set enrichment analysis was performed to explore the potential regulatory pathways involved. The relationship between tumour immune infiltration status and risk score was analysed via Tumour Immune Estimation Resource and CIBERSORT. Finally, we analysed the association between risk score and patient sensitivity to commonly used chemotherapy and targeted therapy agents.

A prognostic model consisting of three inflammatory-related genes (MRPS17, GUF1, and PDK4) was constructed. Independent prognostic analysis revealed that the risk score was a separate prognostic factor in GC patients. According to the risk score, GC patients were stratified into high- and low-risk groups, and patients in the high-risk group had significantly worse prognoses according to age, sex, TNM stage and Lauren type. Consensus clustering identified three subtypes of inflammation that could predict GC prognosis more accurately than traditional grading and staging. Finally, the study revealed that patients in the low-risk group were more sensitive to certain drugs than were those in the high-risk group, indicating a link between inflammation-related genes and drug sensitivity.

In conclusion, we established a novel three-gene prognostic signature that may be useful for predicting the prognosis and personalizing treatment decisions of GC patients.

Nutrient restriction in cancer cells can activate a number of stress response pathways for cell survival. We aimed to determine mechanistically how nutrient depletion in colorectal cancer (CRC) cells leads to cellular adaptation.

Cell survival under nutrient depletion (ND) was evaluated by colony formation and in vivo tumor formation assays. Lysosomes are activated with ND; therefore, we incubated the ND cells with the V-ATPase inhibitor Bafilomycin A1 (ND+Baf). The expression of epithelial and mesenchymal markers with ND+Baf was determined by RNA sequencing and RT-qPCR while motility was determined with an in vivo Chorioallantoic membrane (CAM) assay. Reorganization of cytoskeletal network and lysosomal positioning was determined by immunocytochemistry.

4 different colorectal cancer (CRC) cell lines under ND showed high viability, tumor forming ability and increased expression of one or more epithelial and mesenchymal markers, suggesting the activation of partial (p)-EMT. We observed a further increase in p-EMT markers, numerous membrane protrusions, decreased cell-cell adhesion in 3D, and increased motility in ND+Baf cells. The protrusions in the ND+Baf cells were primarily mediated by microtubules and enabled the relocalization of lysosomes from the perinuclear region to the periphery.

ND activated p-EMT in CRC cells, which was exacerbated by lysosomal alkalinization. The ND+Baf cells also showed numerous protrusions containing lysosomes, which may lead to lysosomal exocytosis and enhanced motility.

Gastric cancer (GC) is prevalent and aggressive, especially when patients have distant lung metastases, which often places patients into advanced stages. By identifying prognostic variables for lung metastasis in GC patients, it may be possible to construct a good prediction model for both overall survival (OS) and the cumulative incidence prediction (CIP) plot of the tumour.

To investigate the predictors of GC with lung metastasis (GCLM) to produce nomograms for OS and generate CIP by using cancer-specific survival (CSS) data.

Data from January 2000 to December 2020 involving 1652 patients with GCLM were obtained from the Surveillance, epidemiology, and end results program database. The major observational endpoint was OS; hence, patients were separated into training and validation groups. Correlation analysis determined various connections. Univariate and multivariate Cox analyses validated the independent predictive factors. Nomogram distinction and calibration were performed with the time-dependent area under the curve (AUC) and calibration curves. To evaluate the accuracy and clinical usefulness of the nomograms, decision curve analysis (DCA) was performed. The clinical utility of the novel prognostic model was compared to that of the 7th edition of the American Joint Committee on Cancer (AJCC) staging system by utilizing Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). Finally, the OS prognostic model and Cox-AJCC risk stratification model modified for the AJCC system were compared.

For the purpose of creating the OS nomogram, a CIP plot based on CSS was generated. Cox multivariate regression analysis identified eleven significant prognostic factors (P < 0.05) related to liver metastasis, bone metastasis, primary site, surgery, regional surgery, treatment sequence, chemotherapy, radiotherapy, positive lymph node count, N staging, and time from diagnosis to treatment. It was clear from the DCA (net benefit > 0), time-dependent ROC curve (training/validation set AUC > 0.7), and calibration curve (reliability slope closer to 45 degrees) results that the OS nomogram demonstrated a high level of predictive efficiency. The OS prediction model (New Model AUC = 0.83) also performed much better than the old Cox-AJCC model (AUC difference between the new model and the old model greater than 0) in terms of risk stratification (P < 0.0001) and verification using the IDI and NRI.

The OS nomogram for GCLM successfully predicts 1- and 3-year OS. Moreover, this approach can help to appropriately classify patients into high-risk and low-risk groups, thereby guiding treatment.

The systemic inflammatory response index (SIRI) has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms. However, research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer surgery.

To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients, who received robotic radical gastric cancer surgery.

Initially, an exhaustive retrieval was performed in the PubMed, the Cochrane Library, EMBASE, Web of Science, and Scopus databases to identify relevant studies. Subsequently, a meta-analysis was executed on 6 cohort studies identifying the value of the SIRI in assessing the survival of gastric cancer patients. Additionally, the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators. The association between preoperative SIRI levels and 5-year overall survival (OS) and disease-free survival (DFS) was assessed.

The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer. Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer. SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities, T-stage, carcinoembryonic antigen levels, the development of early serious postoperative complications, and the rate of lymph node metastasis.

SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

Helicobacter pylori (H. pylori) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology of several different cancers. However, the underlying processes and putative interactions between H. pylori and circRNAs have received very little attention. To address this issue, we explored the interaction between H. pylori and circRNAs to investigate how they might jointly contribute to the occurrence and development of gastric cancer.

Changes in circPGD expression in H. pylori were detected using qRT-PCR. Cell proliferation and migration changes were assayed by colony formation, the CCK-8 assay and the transwell assay. Apoptosis was measured by flow cytometry. Western blot was conducted to detect changes in cell migration, apoptosis, proliferation and inflammation-associated proteins. QRT-PCR was used to measure changes in circPGD and inflammation-associated factors.

We found that H. pylori induced increased circPGD expression in infected human cells and facilitated gastric cancer progression in three ways by promoting cell proliferation and migration, enhancing the inflammatory response, and inhibiting apoptosis.

CircPGD appears to play a role in H. pylori-related gastric cancer and may thus be a viable, novel target for therapeutic intervention.