Treatment Of Gastric Cancer Research Articles

Fructose-1, 6-Bisphosphate Aldolase B Suppresses Glycolysis and Tumor Progression of Gastric Cancer.

Gastric cancer (GC) is believed to be one of the most common digestive tract malignant tumors. However, mounting evidence indicates a link between the glycolysis and tumorigenesis, including gastric cancer. Our research identified 5508 differently expressed mRNAs in gastric cancer. Then, the genes highly associated with tumorigenesis were identified through weighted correlation network analysis (WGCNA). Bioinformatics analysis observed that these hub genes were significantly linked to the regulation of cell cycle, drug metabolism, and glycolysis. Among these hub genes, there is a critical gene involved in glycolysis regulation, namely fructose-bisphosphate B (ALDOB). Analysis based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets revealed that ALDOB was significantly downregulated in GC compared with normal tissues. In addition, cell viability assay confirmed that ALDOB acted as a tumor suppressor. Finally, drug sensitivity analysis revealed that ALDOB increased the sensitivity of gastric cancer cells to most antitumor drugs, especially talazoparib, XAV939, and FTI-277. Our results showed that the expression of ALDOB was significantly lower in GC tissues than in normal tissues. And ALDOB significantly inhibited proliferation and migration, delayed glycolysis in GC cells. Consequently, our study suggests that ALDOB may be a potential target for the clinical treatment of gastric cancer.

A novel prognostic model based on telomere-related lncRNAs in gastric cancer.

Telomeres are specialized structures at the ends of chromosomes that are important for their protection. Over time, long non-coding RNAs (lncRNAs) have gradually come into the spotlight as essential biomarkers of proliferation, migration, and invasion of human malignant tumors. Nevertheless, the impact of telomere-related lncRNAs (TRLs) in gastric cancer is currently unknown. In the present study, we screen the TRLs and identify a prognostic TRLs signature in gastric cancer. First, telomere-related genes (TRGs) were retrieved from the website, and RNA sequencing (RNA-seq) data and clinical data of stomach adenocarcinoma (STAD) patients were gathered from The Cancer Genome Atlas (TCGA) database. Gastric cancer patients' lncRNAs and overall survival (OS) were found to be related using univariate Cox regression analysis. Next, least absolute shrinkage and selection operator (LASSO) regression analysis and multifactorial Cox regression analysis were used to further screen telomere-related differentially expressed lncRNAs (TRDELs), and finally six lncRNAs were obtained, including LINC01537, CFAP61-AS1, DIRC1, RABGAP1L-IT1, DBH-AS1, and REPIN1-AS1. According to these six TRDELs, a prognostic model for gastric cancer was constructed. The samples were divided into the training group and the testing group at random, and the reliability of prognostic model was validated in both groups and overall samples. In addition, we performed Kaplan-Meier (K-M) survival curve analysis, independent prognostic analysis, and functional enrichment analysis to validate the predictive value and independence of the model, as well as immune cell correlation analysis, clustering analysis, and principal component analysis (PCA) to further explore the relationship between this model and the tumor cells. Finally, we performed the drug sensitivity analysis to identify a few small molecules that may have a therapeutic effect on gastric cancer. Finally, we constructed a prognostic model for gastric cancer consisting of six TRDELs. According to the K-M curve, the prognosis of the low-risk group was noticeably superior than that of the high-risk group. Multivariate Cox regression analysis suggested that risk score was an independent prognostic element. Receiver operating characteristic (ROC) curves, nomogram, and calibration curve indicated that the prognostic model had good predictive ability. Functional enrichment analysis demonstrated major pathways with high- and low-risk groups. Next, both tumor microenvironment (TME) and immune correlation analysis showed discrepancy in the high- and low-risk groups. Through drug sensitivity analysis, we screened four small molecules that might be beneficial for gastric cancer treatment. A prognostic model consisting of these six TRDELs was capable to predict the prognosis of gastric cancer patients.

Efficacy and safety of camrelizumab combined with chemotherapy in the first-line treatment of advanced gastric cancer: a single-arm, phase II study.

Chemotherapy with SOX (S-1 and oxaliplatin) regimen showed good efficacy and a favorable safety profile in advanced gastric cancer. Anti-programmed cell death protein 1 (PD-1) antibody camrelizumab also demonstrated antitumor activity in this setting in a phase I study. However, the efficacy and safety of camrelizumab plus SOX for advanced gastric cancer have not been investigated. Thus, this study aimed to address this objective. This phase II study evaluated the efficacy and safety of camrelizumab plus SOX in previously untreated advanced gastric cancer. Patients received camrelizumab (200 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily on days 1-14; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, death, or intolerable toxicity. Camrelizumab was prescribed for up to a year. The primary endpoint was progression-free survival (PFS). The second endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR). A total of 25 patients were enrolled and received at least 1 dose of study drug. The median PFS was 7.4 months [95% confidence interval (CI): 5.6-16.4]. The median OS was 20.2 months (95% CI: 10.5-29.9); ORR was 36% (95% CI: 18.0-57.5%); DCR was 92% (95% CI: 74.0-99.0%). Among the 25 patients, 22 (88%) experienced any-grade adverse events (AEs), and 7 (28%) patients experienced grade ≥3 AEs. Camrelizumab plus SOX showed promising efficacy and an acceptable safety profile as the first-line treatment for advanced gastric cancer.

Potential molecular metabolic mechanisms underlying the effects of cimifugin in gastric cancer through single-cell and bulk RNA sequencing combined with network pharmacology.

Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide, posing a significant clinical challenge due to its complex tumor microenvironment (TME) and metabolic heterogeneity. Despite continuous improvements in treatment strategies including surgery, chemotherapy, and targeted therapies, the metabolic reprogramming in GC continues to impede treatment efficacy, highlighting an urgent need for the development of novel therapeutic strategies. This persistent issue underscores the urgent need for novel therapeutic approaches that can effectively address the diverse and dynamic characteristics of GC. Cimifugin, a traditional Chinese medicine (TCM), has garnered attention for its potential role in alleviating inflammation, neurological disorders, pain, and metabolic disorders. Its multi-targeting properties and minimal side effects suggest a broad potential for cancer management, which is currently being explored. This study aims to delineate the molecular mechanisms that cimifugin may impact within the TME and metabolic pathways of GC, with the expectation of contributing to a deeper understanding of GC and the development of innovative treatment strategies. We identified the GC-related TME cell types and metabolic profiles and pathways by using relevant data from the single-cell RNA sequencing (scRNA-seq) database GSE134520 and the stomach adenocarcinoma (STAD) data set from The Cancer Genome Atlas (TCGA). We also assessed the effects of cimifugin on MKN28 cell proliferation, invasion, and migration. By using six public platforms, we comprehensively predicted the potential biological targets of cimifugin. Clinical prognosis and immunohistochemistry (IHC), molecular docking, and dynamics simulations were used to confirm the clinical relevance and stability of the aforementioned targets. Cimifugin inhibited MKN28 cell proliferation, migration, and invasion. Cimifugin may potentially act on various metabolic pathways in GC, including folate biosynthesis, xenobiotic metabolism via cytochrome P450 (CYP), glutathione metabolism, steroid hormone biosynthesis, and tryptophan metabolism. Cimifugin was noted to stably bind to three significant core targets associated with metabolic reprogramming in GC: AKR1C2, MAOB, and PDE2A; all three targets were strongly expressed in endocrince cells, pit mucous cells (PMCs), and common myeloid progenitors (CMPs). We verified the pharmacological effects of cimifugin on GC cell proliferation, invasion, and migration. AKR1C2, MAOB, and PDE2A were identified as the key targets of cimifugin in GC-related metabolic reprogramming and pathogenesis. Our research provides preliminary insights into the potential therapeutic effects of cimifugin, which could be considered for future exploration in the context of GC treatment.

NUSAP1 promotes gastric cancer radioresistance by inhibiting ubiquitination of ANXA2 and is suppressed by miR-129-5p

BackgroundRadiotherapy is an important strategy for the treatment of advanced gastric cancer (GC), while the radioresistance limits its effectiveness. Nucleolar and spindle associated protein 1 (NUSAP1) was implicated in cancer progression and chemoresistance. However, the underlying mechanisms of NUSAP1 influencing GC radioresistance remain largely unknown.MethodsMeta-analysis was conducted to systematically evaluate the prognostic value of NUSAP1 in human cancers. Gene set enrichment analysis (GSEA) was conducted using The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) datasets. MRNA and protein expressions were detected by qRT-PCR and western blot, respectively. The radiosensitivity of GC cells was observed by colony formation, flow cytometry, comet, immunofluorescence, and animal assays. Immunoprecipitation assay and mass spectrometry were utilized to identify protein associations. MiRNAs binding with NUSAP1 were determined by starbase prediction, luciferase reporter, and RNA immunoprecipitation (RIP) assays.ResultsNUSAP1 high expression predicted worse overall survival (OS) and disease-free survival (DFS) with no statistical heterogeneity through the meta-analysis. Downregulation of NUSAP1 significantly increased GC radiosensitivity by inhibiting colony formation, DNA damage repair, and promoting apoptosis following irradiation. Additionally, NUSAP1 silencing combined with radiation resulted in a synergistic anti-tumor effect in xenograft mouse model. Mechanistically, NUSAP1 interacted with ANXA2, protecting it against protein degradation via impeding its ubiquitination process. NUSAP1 was confirmed as a target of miR-129-5p and negatively regulated by it.ConclusionOur results suggested that NUSAP1 enhanced the radioresistance of GC cells. NUSAP1 could be a promising target to increase GC radiosensitivity.

Re-analysis of single cell and spatial transcriptomics data reveals B cell landscape in gastric cancer microenvironment and its potential crosstalk with tumor cells for clinical prognosis

BackgroundAt present, immunotherapy has become a powerful treatment for advanced gastric cancer (AGC), but not all patients can benefit from it. According to the latest research, the impact of B cell subpopulations on the immune microenvironment of gastric cancer (GC) is unknown. Exploring whether the interaction between B cells and tumor cells in GC affects the effectiveness of immunotherapy has attracted our interest.MethodsThis study involved the re-analysis of single-cell RNA (scRNA) and spatial transcriptomics (ST) data from publicly available datasets. The focus was on investigating the subpopulations and differentiation trajectories of B cells in the gastric cancer (GC) tumor immune microenvironment (TIME). Spatial transcriptomics (ST) and multiple immunofluorescence (mIF) revealed a clear co-localization pattern between B cells and tumor cells. Multiple immunotherapy datasets were collected to identify unique immunotherapy biomarkers. The unique immunotherapeutic potential of targeting CCL28 was validated through a mouse gastric cancer model. In addition, flow cytometry revealed changes in the tumor immune microenvironment targeting CCL28.ResultsThe re-analysis of ST data from multiple cancer types revealed a co-localization pattern between B cells and tumor cells. A significant number of IgA plasma cells were identified in the GC TIME. Five different tumor-infiltrating B cell subpopulations and two unique B cell differentiation trajectories were characterized, along with seven GC-related states. By analyzing the communication between GC cells and B cells, it was further discovered that tumor cells can influence and recruit plasma cells through CCL28-CCR10 signaling. Additionally, there was a crosstalk between GC cells and B cells. Finally, we identified the LAMA/CD44 signaling axis as a potential prognostic marker for immunotherapy through a large amount of immunotherapy data. We also validated through various animal tumor models that targeting CCL28 can significantly promote CD8+T cell infiltration and function in the TME by regulating B cell and plasma cell functions, and has the ability to synergize immunotherapy.ConclusionThe co-localization and crosstalk between GC cells and B cells significantly affect the efficacy of immunotherapy, and inhibiting the CCL28-CCR10 signal axis is a potential immunotherapy target for GC. Meanwhile, LAMA/CD44 pair may be a potential adverse indicator for immunotherapy and tumor prognosis.

Enhancement of the stability and cytotoxicity of berberine by liposomal nanocarriers for gastric cancer treatment and its application in gummy candy

Enhancement of the stability and cytotoxicity of berberine by liposomal nanocarriers for gastric cancer treatment and its application in gummy candy

Open, Laparoscopy-assisted, Robotic-assisted Distal Gastrectomy for Gastric Cancer: Evidence from Randomized Clinical Trials.

Gastric cancer (GC) is the fifth most common cancer and fourth leading cause of cancer-related deaths worldwide. Gastrectomy with lymphadenectomy is the standard treatment for both early and locally advanced GC. Laparoscopic surgery has been widely used for decades for the treatment of benign diseases, such as cholecystectomy and appendectomy. The use of laparoscopy-assisted distal gastrectomy (LADG) for the treatment of gastric cancer was first described by Kitano in 1994. Since then, the number of gastric cancer cases treated with LADG has gradually increased. Recently, robot-assisted gastrectomy (RDG) has also been introduced in the treatment of GC. To date, several randomized control trials (RCT) have been conducted to evaluate the safety, feasibility, and efficacy of LADG and RDG in comparison to open distal gastrectomy (ODG). However, the short- and long-term oncological outcomes of LADG and RDG remain controversial and have not been fully evaluated. To optimize GC treatment, especially gastrectomy with lymphadenectomy, it is necessary to understand the characteristics of each approach before gastric cancer treatment. This review summarizes the background, current status, and future perspectives of LADG and RDG in GC treatment using RCT data.

Unlocking the Potential: Epstein-Barr Virus (EBV) in Gastric Cancer and Future Treatment Prospects, a Literature Review.

Gastric cancer (GC) is a complex disease with various etiologies. While Helicobacter pylori infection is still one of the leading risk factors for GC, increasing evidence suggests a link between GC and other infective agents such as Epstein Bar Virus (EBV). EBV-associated gastric cancer (EBVaGC) is now recognized as a distinct subgroup of GC, and the complex interactions between the virus and gastric mucosa may influence its development. A recent integrative analysis of the genome and proteome of GC tissues by The Cancer Genome Atlas project has identified EBVaGC as a specific subtype characterized by PIK3CA and ARID1A mutations, extensive DNA hyper-methylation, and activation of immune signaling pathways. These molecular characteristics are markers of the unique molecular profile of this subset of GC and are potential targets for therapy. This review aims to provide an overview of the current knowledge on EBVaGC. It will focus on the epidemiology, clinic-pathological features, and genetic characteristics of EBVaGC. Additionally, it will discuss recent data indicating the potential use of EBV infection as a predictive biomarker of response to chemotherapy and immune checkpoint inhibitors. The review also delves into potential therapeutic approaches for EBVaGC, including targeted therapies and adoptive immunotherapy, highlighting the promising potential of EBV as a therapeutic target.

TRIP13 regulates progression of gastric cancer through stabilising the expression of DDX21

GC (Gastric cancer) is one of the most common malignant tumours, with over 95% of gastric cancer patients being adenocarcinoma and most gastric cancer patients having no apparent symptoms in the early stages. Finding biomarkers for early screening of gastric cancer and exploring new targets for gastric cancer treatment are urgent problems to be solved in the treatment of gastric cancer, with significant clinical outcomes for the survival rate of gastric cancer patients. The AAA+ family ATPase thyroid hormone receptor-interacting protein 13 (TRIP13) has been reported to play an essential role in developing various tumours. However, the biological function and molecular mechanism of TRIP13 in gastric cancer remain unclear. This study confirms that TRIP13 is highly expressed in gastric cancer tissue samples and that TRIP13 participates in the proliferation, migration, invasion in vitro, and tumourigenesis and metastasis in vivo of gastric cancer cells. Mechanistically, this study confirms that TRIP13 directly interacts with DDX21 and stabilises its expression by restraining its ubiquitination degradation, thereby promoting gastric cancer progression. Additionally, histone deacetylase 1 (HDAC1) is an upstream factor of TRIP13, which could target the TRIP13 promoter region to promote the proliferation, migration, and invasion of gastric cancer cells. These results indicate that TRIP13 serve is a promising biomarker for the treating of gastric cancer patients, and the HDAC1-TRIP13/DDX21 axis might provide a solid theoretical basis for clinical treatment of gastric cancer patients.

The Impact of Pembrolizumab as a Salvage Therapy Based on HER2 Expression in Advanced Gastric Cancer.

Immune checkpoint inhibitors (ICIs) are used as salvage treatments for advanced gastric cancer (AGC) regardless of HER2 status. This study assessed the efficacy of ICIs based on HER2 expression in AGC patients who received pembrolizumab as salvage monotherapy at Samsung Medical Center from November 2017 to March 2023. HER2 status was determined via immunohistochemistry, and tumor response and survival outcomes were compared accordingly. Among the 113 patients analyzed, with a median age of 61 years and 64.6% being male, 12 patients (10.6%) were HER2-positive, and 101 patients (89.4%) were HER2-negative. Of 92 evaluable patients, none had a complete response. However, 50% of HER2-positive patients had a partial response, compared to 4.9% of HER2-negative patients (p < 0.001). The disease control rate was 70% in HER2-positive and 37.8% in HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). Pembrolizumab as a salvage chemotherapy for the treatment of AGC demonstrated superior effectiveness in HER2-positive patients compared with HER2-negative patients.

Predicting gastric cancer response to anti-HER2 therapy or anti-HER2 combined immunotherapy based on multi-modal data

The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P < 0.05). These findings not only highlight the significance of multi-modal data analysis in enhancing treatment evaluation and personalized medicine for HER2-positive gastric cancer, but also the potential and clinical value of our model.

The efficacy and safety of pH-responsive and photothermal-sensitive multifunctional nanoparticles loaded with cryptotanshinone for the treatment of gastric cancer.

A multifunctional polydopamine/mesoporous silica nanoparticles loaded cryptotanshinone (PDA/MSN@CTS) was synthesized and subjected to investigating its physicochemical properties and anti-gastric cancer (GC) effects. Utilizing network pharmacology and molecular docking techniques, CTS was identified as our final research target. The structural morphology and physicochemical properties of PDA/MSN@CTS were examined. Near-infrared (NIR) laser was employed to evaluate the photothermal properties of the PDA/MSN@CTS, along with pH-responsive and NIR-triggered release assessments. In vitro experiments evaluated the impact of PDA/MSN@CTS on the malignant behavior of AGS gastric cells. A subcutaneous tumor model was further established to evaluate the in vivo safety of PDA/MSN@CTS. Furthermore, the in vivo photothermal efficacy of PDA/MSN@CTS, in addition to its combined effect with photothermal therapy (PTT), was investigated. Uniform and stable PDA/MSN@CTS had been successfully synthesized and demonstrated efficient release under tumor environment and NIR irradiation. Upon increasing NIR laser conditions, in vivo cytotoxicity, apoptosis rate, reactive oxygen species scavenging ability, and suppression of migration and invasion of AGS cells by PDA/MSN@CTS were significantly enhanced. In vivo assessments revealed excellent blood compatibility and biosafety of PDA/MSN@CTS, alongside robust tumor tissue targeting. Combining nanoparticles with PTT facilitated the anti-GC effects of PDA/MSN@CTS. Compared to free drugs, PDA/MSN@CTS exhibits higher selectivity towards cancer cells, demonstrating effective anticancer activity and biocompatibility both in vitro and in vivo. Furthermore, our nanomaterial possesses excellent photothermal properties, and under NIR conditions, PDA/MSN@CTS exhibits synergistic therapeutic effects.

Chemotherapy, immunotherapy, and antiangiogenesis: Emerging trends in the comprehensive treatment of advanced gastric cancer

Chemotherapy, immunotherapy, and antiangiogenesis: Emerging trends in the comprehensive treatment of advanced gastric cancer

A real-world survey on expensive drugs used as first-line chemotherapy in patients with HER2-negative unresectable advanced/recurrent gastric cancer in the stomach cancer study group of the Japan clinical oncology group.

Molecular-targeted drugs and immune checkpoint inhibitors have been developed for various malignant diseases, thereby improving clinical outcomes. However, these drugs are expensive, and few studies have assessed their actual use and costs in Japan. This study aimed to survey the use and costs of first-line chemotherapy for advanced/recurrent gastric cancer (AGC) in real-world settings. The survey included patients with human epidermal growth factor receptor type2 (HER2)-negative AGC who initiated first-line chemotherapy from January 2022 to December 2022 at the participating 92 institutions in the Japan Clinical Oncology Group. Data on the regimens were collected using Google Forms. A regimen that costs >500 000 Japanese yen (JPY) per month was defined as expensive. Data on chemotherapy regimens were collected from 2173 patients at all 92 institutions between March 2023 and May 2023. We analyzed 2113 patients who underwent the chemotherapy with recommended regimens and conditionally recommended regimens according to the Japanese Gastric Cancer Treatment Guidelines sixth edition. The expensive regimens were triplet chemotherapy with fluoropyrimidine (S-1 or capecitabine or 5-fluorouracil/levofolinate), oxaliplatin, and nivolumab. Their monthly costs ranged from 767 648 to 771 046 JPY. Nivolumab-containing regimens cost more than 20 times the price of conventional chemotherapy with fluoropyrimidine and oxaliplatin. These regimens were used in 1416 (67%) of 2113 patients: in 71% of patients aged ≤74years and in 59% of patients aged ≥75years. The regimens with >20-fold cost of conventional chemotherapy were used as first-line chemotherapy in two-thirds of patients and more than half even in the elderly population with HER2-negative AGC. This finding is important for future health economic studies on drug cost-efficacy.

RARB associated with MSI, affects progression and prognosis of gastric cancer

Microsatellite instability (MSI) has been widely acknowledged as an important factor regulating tumor intrinsic biological behavior and affecting the survival of gastric cancer patients. Here, we firstly identified the RARB as a gene associated with MSI gastric cancer. RARB was downregulated in human gastric cancer tissues compared to paired paracancerous tissues, Knockdown of RARB accelerated the proliferation, invasion and migration of cancer cells in vitro. Mechanismly, RARB knockdown promoted epithelial-mesenchymal transition (EMT) process of gastric cancer. However, RARBLow patients exhibited better survival compared to RARBHigh patients. Further study revealed that RARB expression was inversely correlated with MSI status and immune infiltrates in vivo. Thus, RARB may be a potential target for the treatment of gastric cancer.

Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis.

The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.

Prediction of CD8+T lymphocyte infiltration levels in gastric cancer from contrast-enhanced CT and clinical factors using machine learning.

CD8+ T lymphocyte infiltration is closely associated with the prognosis and immunotherapy response of gastric cancer (GC). For now, the examination of CD8 infiltration levels relies on endoscopic biopsy, which is invasive and unsuitable for longitude assessment during anti-tumor therapy. This work aims to develop and validate a noninvasive workflow based on contrast-enhanced CT (CECT) images to evaluate the CD8+ T-cell infiltration profiles of GC. GC patients were retrospectively and consecutively enrolled and randomly assigned to the training (validation) or test cohort at a 7:3 ratio. All patients were binary classified into the CD8-high (infiltrated proportion≥20%) or CD8-low group (infiltrated proportion<20%) group. A total of 1170 radiomics features were extracted from each presurgical CECT series. After feature selection, fifteen radiomics features were transmitted to three independent machine-learning models for the computation of predictive radiological scores. Multilayer perceptron (MLP) was applied to merge the radiological scores with clinical factors. The predictive efficacy of the radiological scores and of the combined model was evaluated by receiver operating characteristic curve, calibration curve, and decision curve analysis in both the training and test cohorts. A total of 210 patients were enrolled in this study (mean age: 63.22±8.74years, 151 men), and were randomly assigned to the training set (n=147) or the test set (n=63). The merged radiological score was correlated with CD8 infiltration in both the training (p=1.8e-10) and test cohorts (p=0.00026). The combined model integrating the radiological scores and clinical features achieved an area under the curve (AUC) value of 0.916 (95% CI: 0.872-0.960) in the training set and 0.844 (95% CI: 0.742-0.946) in the test set for classifying CD8-high GCs. The model was well-calibrated and exhibited net benefit over "treat-all" and"treat-none" strategies in decision curve analysis. Artificial intelligent systems combining radiological features and clinical factors could accurately predict CD8 infiltration levels of GC, which may benefit personalized treatment of GC in the context of immunotherapy.

Radiomics analysis in predicting vascular invasion in gastric cancer based on enhanced CT: a preliminary study

BackgroundVascular invasion (VI) is closely related to the metastasis, recurrence, prognosis, and treatment of gastric cancer. Currently, predicting VI preoperatively using traditional clinical examinations alone remains challenging. This study aims to explore the value of radiomics analysis based on preoperative enhanced CT images in predicting VI in gastric cancer.MethodsWe retrospectively analyzed 194 patients with gastric adenocarcinoma who underwent enhanced CT examination. Based on pathology analysis, patients were divided into the VI group (n = 43) and the non-VI group (n = 151). Radiomics features were extracted from arterial phase (AP) and portal venous phase (PP) CT images. The radiomics score (Rad-score) was then calculated. Prediction models based on image features, clinical factors, and a combination of both were constructed. The diagnostic efficiency and clinical usefulness of the models were evaluated using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).ResultsThe combined prediction model included the Rad-score of AP, the Rad-score of PP, Ki-67, and Lauren classification. In the training group, the area under the curve (AUC) of the combined prediction model was 0.83 (95% CI 0.76–0.89), with a sensitivity of 64.52% and a specificity of 92.45%. In the validation group, the AUC was 0.80 (95% CI 0.67–0.89), with a sensitivity of 66.67% and a specificity of 88.89%. DCA indicated that the combined prediction model might have a greater net clinical benefit than the clinical model alone.ConclusionThe integrated models, incorporating enhanced CT radiomics features, Ki-67, and clinical factors, demonstrate significant predictive capability for VI. Moreover, the radiomics model has the potential to optimize personalized clinical treatment selection and patient prognosis assessment.

Identification of an autophagy- and macropinocytosis-related prognostic signature for the prediction of prognosis and therapeutic response in gastric cancer.

Traditional liquid biopsy markers show a low rate of positivity and accurate in gastric cancer. With the rapid advancement of sequencing technology, scientists have identified promising research avenues in this field. Autophagy and macropinocytosis utilize diverse pathways and mechanisms to supply resources and fuel for tumor growth. Nonetheless, their potential interplay introduces an untapped avenue for the discovery of novel tumor biomarkers. To develop an innovative prognostic signature based on autophagy- and micropinocytosis-related genes, with the aim to predict the outcome and therapeutic response of gastric cancer patients. Additionally, to validate the prognostic impact of this signature, and elucidate the role of representative molecules in gastric cancer. To construct and validate a prognostic signature for gastric cancer, bioinformatics methods such as COX regression, LASSO regression, survival analysis, ROC curve, and nomogram were utilized based on the sequencing and clinical data of gastric cancer patients retrieved from the TCGA and GEO databases. GSEA functional enrichment analyses were employed to predict the biological functions. Meanwhile, qRT-PCR and Western blot experiments were utilized to quantify the mRNA and protein expression levels. Furthermore, the EdU assay and colony formation assay were utilized to examine the cell proliferation ability while the Transwell assays were conducted to assess the migration and invasion abilities of gastric cancer cells. Through consistency clustering and univariate COX analyses, potential prognostic genes involved in both autophagy and macropinocytosis were identified. Based on these genes, a 9-gene signature was constructed, which demonstrated high accuracy in predicting gastric cancer patients' survival period, immunotherapeutic response, and chemotherapy drug tolerance. Furthermore, qRT-PCR analyses of gastric cancer tissue samples showed that the representative genes of this signature were aberrantly overexpressed in gastric cancer, with MATN3, as the most notable molecule, exhibiting significant carcinogenic effects on cancer cells by actively regulating their proliferation, migration, and invasion abilities. Our newly created prognostic signature possesses significant potential as a biomarker for gastric cancer, while MATN3 is identified as an oncogenic factor in gastric cancer. This brings to light new perspectives, which can contribute to enhancing the diagnosis and treatment of gastric cancer.