Peritoneal Metastasis Of Gastric Cancer Research Articles

Recent progress and future prospects of treatment for peritoneal metastasis in gastric cancer

Peritoneal metastasis is one of the most frequent patterns of metastasis in gastric cancer, and remains a major unmet clinical problem. Thus, systemic chemotherapy remains the mainstay of treatment for gastric cancer with peritoneal metastasis. In well-selected patients, the reasonable combination of cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and neoadjuvant intraperitoneal chemotherapy with systemic chemotherapy will bring significant survival benefits to patients with gastric cancer peritoneal metastasis. In patients with high-risk factors, prophylactic therapy may reduce the risk of peritoneal recurrence, and improves survival after radical gastrectomy. However, high-quality randomized controlled trials will be needed to determine which modality is better. The safety and efficacy of intraoperative extensive intraperitoneal lavage as a preventive measure has not been proven. The safety of HIPEC also requires further evaluation. HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy have achieved good results in conversion therapy, and it is necessary to find more efficient and low-toxicity therapeutic modalities and screen out the potential benefit population. The efficacy of CRS combined with HIPEC on peritoneal metastasis in gastric cancer has been preliminarily validated, and with the completion of clinical studies such as PERISCOPE II, more evidence will be available.

FMO family may serve as novel marker and potential therapeutic target for the peritoneal metastasis in gastric cancer.

To explore the relationship between flavin-containing monooxygenases (FMOs) and peritoneal metastasis (PM) in gastric cancer (GC). TIMER 2.0 was used to perform pan-cancer analysis and assess the correlation between the expression of FMOs and cancers. A dataset from The Cancer Genome Atlas (TCGA) was used to analyze the correlation between FMOs and clinicopathological features of GC. PM is well established as the most common mode of metastasis in GC. To further analyze the correlation between FMOs and PM of GC, a dataset was obtained from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database. The results were validated by immunohistochemistry. The relationship between FMOs and PM of GC was explored, and a novel PM risk signature was constructed by least absolute shrinkage and selection operator (LASSO) regression analysis. The regression model's validity was tested by multisampling. A nomogram was established based on the model for predicting PM in GC patients. The mechanism of FMOs in GC patients presenting with PM was assessed by conducting Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses in TCGA and GEO datasets. Finally, the potential relationship between FMOs and immunotherapy was analyzed. The pan-cancer analysis in TCGA and GEO datasets showed that FMO1 was upregulated, while FMO2 and FMO4 were downregulated in GC. Moreover, FMO1 and FMO2 correlated positively with the T and N stage of GC in the TCGA dataset. FMO1 and FMO2 expression was a risk factor for GC (hazard ratio: 1.112 and 1.185). The overexpression of FMO1 was significantly correlated with worse disease-free-survival (DFS) and overall survival (OS). However, no relationship was found between FMO2 expression in GC and DFS and OS. PM was highly prevalent among GC patients and typically associated with a worse prognosis. FMO1 was highly expressed in GC with PM. FMO1 and FMO2 were positively correlated with PM in GC. We identified a 12-gene panel for predicting the PM risk signature by LASSO (Area Under Curve (AUC) = 0.948, 95%CI: 0.896-1.000). A 10-gene panel for PM prediction was identified (AUC = 0.932, 95%CI: 0.874-0.990), comprising FMO1 and FMO2. To establish a model for clinical application, a 7-gene panel was established (AUC = 0.927, 95% CI: 0.877-0.977) and successfully validated by multisampling. (AUC = 0.892, 95% CI: 0.878-0.906). GO and KEGG analyses suggest that FMO1 and FMO2 regulate the extracellular matrix and cell adhesion. FMO1 and FMO2 were positively correlated with the immune score of GC, and their expression was associated with the infiltration of immune cells. PM in GC is strongly correlated with FMOs. Overall, FMO1 and FMO2 have huge prospects for application as novel diagnostic and therapeutic targets.

Biomimetic single-atom nanozyme system for efficient inhibition of gastric cancer ascites via SO2 gas-enhanced nanocatalytic cancer therapy

Peritoneal metastasis is a frequent cause of death in gastric cancer, and it is newer mainly treated by hyperthermic intraperitoneal chemotherapy (HIPEC),whereas the patients experience serious side effects.Thus it is urgent to develop new alternatives, one example being Cu single-atom nanozymes (SAZ) with peroxidase (POD)-like activity and which have good nanocatalytic tumor therapy (NCT) capabilities. A previously described approach was used to produce platelet membrane vesicles (PV) and Cu SAZ. However, insufficient hydrogen peroxide (H2O2) limit NCT effects. Therefore, to overcome these limitations, through physical extrusion, an SO2 prodrug (benzothiazole sulfinate, BTS) and Cu SAZ were combined with PV to create PSB. BTS were able to release SO2 before inducing SO3− that can cause cell apoptosis. In addition, it can also down-regulate glutathione (GSH) while up-regulating H2O2 to significantly improve the catalytic ability of Cu SAZ. This study proved that PSB could suppress over 90% of the tumor while displaying good tumor-targeting abilities alongside great biocompability. Thus, by innovatively combining gas therapy with NCT, the system developed in this study not only provide a new strategy for addressing peritoneal metastasis of gastric cancer, but also offers useful insights into designing a new generation of cancer therapy for potential clinical applications.

Peritoneal high-fat environment promotes peritoneal metastasis of gastric cancer cells through activation of NSUN2-mediated ORAI2 m5C modification.

Peritoneal metastasis (PM) is an important metastatic modality of gastric cancer (GC).It is associated with poor prognosis. The underlying molecular mechanism of PM remains elusive. 5-Methylcytosine (m5C), a posttranscriptional RNA modification, involves in the progression of many tumors. However, its role in GC peritoneal metastasis remains unclear. In our study, transcriptome results suggested that NSUN2 expression was significantly upregulated in PM. And patients with high NSUN2 expression of PM predicted a worse prognosis. Mechanistically, NSUN2 regulates ORAI2 mRNA stability by m5C modification, thereby promoting ORAI2 expression and further promoting peritoneal metastasis and colonization of GC. YBX1 acts as a "reader" by binding to the ORAI2 m5C modification site. Following the uptake of fatty acids from omental adipocytes by GC cells, the transcription factor E2F1 was upregulated, which further promoted the expression of NSUN2 through cis-element. Briefly, these results revealed that peritoneal adipocytes provide fatty acid for GC cells, thus contributing to the elevation of E2F1 and NSUN2 through AMPK pathway, and upregulated NSUN2 activates the key gene ORAI2 through m5C modification, thereby promoting peritoneal metastasis and colonization of gastric cancer.

Can visceral fat parameters based on computed tomography be used to predict occult peritoneal metastasis in gastric cancer?

The preoperative prediction of peritoneal metastasis (PM) in gastric cancer would prevent unnecessary surgery and promptly indicate an appropriate treatment plan. To explore the predictive value of visceral fat (VF) parameters obtained from preoperative computed tomography (CT) images for occult PM and to develop an individualized model for predicting occult PM in patients with gastric carcinoma (GC). A total of 128 confirmed GC cases (84 male and 44 female patients) that underwent CT scans were analyzed and categorized into PM-positive (n = 43) and PM-negative (n = 85) groups. The clinical characteristics and VF parameters of two regions of interest (ROIs) were collected. Univariate and stratified analyses based on VF volume were performed to screen for predictive characteristics for occult PM. Prediction models with and without VF parameters were established by multivariable logistic regression analysis. The mean attenuations of VFROI 1 and VFROI 2 varied significantly between the PM-positive and PM-negative groups (P = 0.044 and 0.001, respectively). The areas under the receiver operating characteristic curves (AUCs) of VFROI 1 and VFROI 2 were 0.599 and 0.657, respectively. The mean attenuation of VFROI 2 was included in the final prediction combined model, but not an independent risk factor of PM (P = 0.068). No significant difference was observed between the models with and without mean attenuation of VF (AUC: 0.749 vs 0.730, P = 0.339). The mean attenuation of VF is a potential auxiliary parameter for predicting occult PM in patients with GC.

Abstract 134: Lymph node metastases are seeded via two distinct ways in phylogenetic study of gastric cancer

Abstract Backgrounds: Gastric cancer (GC) ranked 5th and 8th on the list of cancer related deaths worldwide and in Taiwan, respectively. Due to its high frequency of lymph node spread, lymph node dissection has become a standard procedure in surgical treatment. A randomized trial showed that patients who underwent D2 lymphadenectomy had a better 5-year survival outcome than ones who had D1 dissection in advanced gastric cancer, implying the D2 lymph node might serve as an outpost before tumor cells spread to distant organs. This clinical observation raises a possibility that the regional lymphatic spread could be under strict selection but not a passive process. Materials and Methods: To understand the evolutionary relationship between primary tumors, perigastric lymph nodes, and second tier of lymph nodes in the extra-perigastric area, we reconstruct their phylogeny using genetic variants in hypermutable DNA regions where the mutation rate is 102~104-fold than unique sequence. We have assembled a cohort of 10 gastric cancer patients, including intestinal-, diffuse- and mixed type GC. For each case, we collected all workable lymph node metastases and intensely sampled primary tumors. On average, we have over fifteen samples per case on the phylogenetic tree. Results: Preliminary data of the first two patients show high heterogeneity within primary tumors as well as between different lesions of lymph nodes or peritoneal metastases in gastric cancer. Interestingly, in stark contrast to all other lymph node metastases which intermingle with primary tumors, a clade consisting of one proximal and one distal lymph node with a bootstrap value above 90% is observed in each phylogeny, and it is worth noting that samples on these clades are from intestinal type tumor. Conclusion: Our results indicate that most tumor cells arrive both regional and distal lymph nodes passively via lymphatic drainage in GC while a selective process also exists which coincides with clinical observation. Whether the existence of tumor cells under a relatively stricter selection process would lead to different clinical outcomes is under investigation. Citation Format: Pei-Chi Cheng, Wei-Ting Hung, Yung-Ming Jeng, I-Rue Lai. Lymph node metastases are seeded via two distinct ways in phylogenetic study of gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 134.

Abstract 1399: Genomic profiling of gastric cancer with peritoneal metastasis identifies molecular subtypes and a potential molecular-guided therapeutic strategy for intractable gastric cancer

Abstract Patients with peritoneal metastasis frequently identified in advanced gastric cancer (GC) have a poor prognosis with a median survival of 3-6 months. Because of innate resistance to treatment, these patients have limited therapeutic efficacy and contribute to high mortality. Therefore, it is necessary to understand the molecular characteristics of peritoneal metastasis and search for applicable drugs. This study aims to understand the biological characteristics of peritoneal metastasis in GC through integrative genomic analysis.A total of 66 GC cell lines were used, of which 11 were derived from the stomach, 49 from peritoneal and pleural fluids, and 6 from other origins. Targeted sequencing and RNA sequencing data were obtained from the Songdang Institute for Cancer Research (SICR) database. Cell lines were clustered into EMT and Non-EMT groups according to the expression profiles of 200 genes belonging to the EMT gene set (Nature Cancer, 2021, 2.9: 962-977.). We used gene sets from the Molecular Signatures Database v.7.0.Hierarchical clustering separated the 49 cell lines derived from peritoneal and pleural fluids into two distinct clusters (EMT group, n=20 and Non-EMT group, n=29). Cell lines in the EMT group were classified as GS (65%, 13/20) and CIN (35%, 7/20), whereas cell lines in the Non-EMT group were classified as EBV-positive (3.4%, 1/29), MSI-H (6.9%, 2/29), GS (37.9%, 11/29), and CIN (51.7%, 15/29). The gene set enrichment analysis (GSEA) revealed that gene sets (HALLMARK_EPITHELIAL_MESENCHYMAL_TRANSITION, CORDENONSI_YAP_CONSERVED_SIGNATURE, and FRIDMAN_SENESCENCE_UP) shows statistically significant differences between the two compared groups. Gene expression levels were significantly different between the EMT and Non-EMT group. In detail, YAP/TEAD pathway related genes (TEAD1, TEAD3, CYR61, DKK1, SLC7A5, SLC2A3) and TGF-β pathway related genes (SMAD3, TGFβ1, TGFβ2, BMP1, INHBA) showed a higher expression level in the EMT group compared to the Non-EMT group (p<0.05). Interestingly, GSEA between the EMT and Non-EMT groups of the GS subtype revealed that gene set CORDENONSI YAP CONSERVED SIGNATURE was enriched in the EMT group. Gene set FOROUTAN_TGFB_EMT_UP, on the other hand, was enriched in the EMT group of the CIN subtype (p<0.05).In conclusion, we identified differences in gene expression levels according to molecular subtypes in GC cell lines with peritoneal metastasis. It can provide useful information to gain new insight into the mechanism of peritoneal metastasis and improve successful treatment options. Furthermore, our results suggest that YAP/TEAD may be considered a potential therapeutic target for GC with peritoneal metastasis. Citation Format: Juin Park, Woo Sun Kwon, Jingmin Che, Tae Soo Kim, Sang Woo Cho, Eun Seo Kim, Hyun Cheol Chung, Sun Young Rha. Genomic profiling of gastric cancer with peritoneal metastasis identifies molecular subtypes and a potential molecular-guided therapeutic strategy for intractable gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1399.

Intraperitoneal transfer of microRNA-29b-containing small extracellular vesicles can suppress peritoneal metastases of gastric cancer.

Small extracellular vesicles (sEV) contain various microRNAs (miRNAs) and play crucial roles in the tumor metastatic process. Although miR-29b levels in peritoneal exosomes were markedly reduced in patients with peritoneal metastases (PM), their role has not been fully clarified. In this study, we asked whether the replacement of miR-29b can affect the development of PM in a murine model. UE6E7T-12, human bone marrow-derived mesenchymal stem cells (BMSCs), were transfected with miR-29b-integrating recombinant lentiviral vector and sEV were isolated from culture supernatants using ultracentrifugation. The sEV contained markedly increased amounts of miR-29b compared with negative controls. Treatment with transforming growth factor-β1 decreased the expression of E-cadherin and calretinin with increased expression of vimentin and fibronectin on human omental tissue-derived mesothelial cells (HPMCs). However, the effects were totally abrogated by adding miR-29b-rich sEV. The sEV inhibited proliferation and migration of HPMCs by 15% (p < 0.005, n = 6) and 70% (p < 0.005, n = 6), respectively, and inhibited adhesion of NUGC-4 and MKN45 to HPMCs by 90% (p < 0.0001, n = 5) and 77% (p < 0.0001, n = 5), respectively. MicroRNA-29b-rich murine sEV were similarly obtained using mouse BMSCs and examined for in vivo effects with a syngeneic murine model using YTN16P, a highly metastatic clone of gastric cancer cell. Intraperitoneal (IP) transfer of the sEV every 3 days markedly reduced the number of PM from YTN16P in the mesentery (p < 0.05, n = 6) and the omentum (p < 0.05, n = 6). Bone marrow mesenchymal stem cell-derived sEV are a useful carrier for IP administration of miR-29b, which can suppress the development of PM of gastric cancer.

Construction of a nomogram model for predicting peritoneal metastasis in gastric cancer: focused on cardiophrenic angle lymph node features

BackgroundA different treatment was used when peritoneal metastases (PM) occurred in patients with gastric cancer (GC). Certain cancers' peritoneal metastasis could be predicted by the cardiophrenic angle lymph node (CALN). This study aimed to establish a predictive model for PM of gastric cancer based on the CALN.MethodsOur center retrospectively analyzed all GC patients between January 2017 and October 2019. Pre-surgery computed tomography (CT) scans were performed on all patients. The clinicopathological and CALN features were recorded. PM risk factors were identified via univariate and multivariate logistic regression analyses. The receiver operator characteristic (ROC) curves were generated using these CALN values. Using the calibration plot, the model fit was assessed. A decision curve analysis (DCA) was conducted to assess the clinical utility.Results126 of 483 (26.1%) patients were confirmed as having peritoneal metastasis. These relevant factors were associated with PM: age, sex, T stage, N stage, enlarged retroperitoneal lymph nodes (ERLN), CALN, the long diameter of the largest CALN (LD of LCALN), the short diameter of the largest CALN (SD of LCALN), and the number of CALNs (N of CALNs). The multivariate analysis illustrated that the LD of LCALN (OR = 2.752, p < 0.001) was PM’s independent risk factor in GC patients. The area under the curve (AUC) of the model was 0.907 (95% CI 0.872–0.941), demonstrating good performance in the predictive value of PM. There is excellent calibration evident from the calibration plot, which is close to the diagonal. The DCA was presented for the nomogram.ConclusionCALN could predict gastric cancer peritoneal metastasis. The model in this study provided a powerful predictive tool for determining PM in GC patients and helping clinicians allocate treatment.

Single-cell sequencing of ascites fluid illustrates heterogeneity and therapy-induced evolution during gastric cancer peritoneal metastasis

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a high-proliferative phenotype. Transitions occur via the recently described, autophagy-dependent plasticity program, paligenosis. Two autophagy-related genes (MARCKS and TXNIP) mark high-plasticity GC with poorer prognosis, and autophagy inhibitors induce apoptosis in patient-derived organoids. Our findings provide insights into the developmental trajectories of cancer/immune cells underlying GCPM progression and therapy resistance.

Clinical significance of CA125 in unresectable pancreatic cancer treated with first-line chemotherapy.

745 Background: Serum CA125 is a potential biomarker for diagnosis of peritoneal metastasis in gastric cancer. However, its significance of pancreatic cancer (PC) has not been investigated. Therefore, we aimed to clarify association between serum CA125 and ascites burden, and its kinetics during first-line chemotherapy for PC. Methods: This multicenter retrospective study comprised PC patients who received FOLFIRINOX or gemcitabine plus nab-paclitaxel in first-line setting between Jan 2014 and Dec 2021. Patient background and treatment outcome was assessed in CA125 elevated and non-elevated group before chemotherapy. The CA125 kinetics after chemotherapy was calculated based on baseline and first measure of CA125. Further, the association between early CA125 change and clinical response during chemotherapy were evaluated based on optimal cut off value calculated receiver operating characteristic (ROC) curve analysis. Results: A total 109 patients from 3 hospitals were assessable. The overall survival (OS) was significantly shorter in elevated group than that in non-elevated group (median, 10.7 vs. 21.3 months, p = 0.0002). The median value of CA125 before chemotherapy was elevated according to ascites burden (Non, 36U/ml; mild, 173U/ml; moderate/severe, 575U/ml; p &lt; 0.0001). CA125 elevation, CA19-9 elevation, poor performance status and poor glasgow prognostic score were independent prognostic factors in multivariate analysis. After chemotherapy, the median first-time measure of CA125 was performed in day 41. Among patients with peritoneal dissemination, the median change of CA125 was correlated with clinical response (CR/PR, -0.55%/day; SD, -0.24%/day; PD, 3.35%/day, p = 0.004). After chemotherapy, first-time measure of CA125 was performed in a median of day 41. According to the ROC curve analysis, the optimal cut-off value of increase in CA125 for progressive disease was 1.56 %/day (specificity 94.1%, sensitivity 80%). The median PFS and OS were 1.4 and 6.6 months in increased group and 3.3 months and 14.0 months in non-increased group, respectively (p = 0.016 and p = 0.028). Conclusions: CA125 is considered a clinically useful marker in unresectable PC treated with first-line chemotherapy because CA125 above the ULN is a poor prognostic factor for OS and an increased CA125 can be an early predictor of progression in patients with peritoneal dissemination.

Identification and validation of crucial lnc-TRIM28-14 and hub genes promoting gastric cancer peritoneal metastasis

BackgroundGastric cancer peritoneal metastasis (GCPM) is an important cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) play a key role in the regulation of GCPM, but the underlying mechanisms have not been elucidated.MethodsHigh-throughput RNA sequencing (RNA-seq) was performed on four groups of clinical specimens (non-metastatic gastric cancer primary tumor, adjacent normal gastric mucosal tissue, gastric cancer primary tumor with peritoneal metastasis and adjacent normal gastric mucosal tissue). After sequencing, many lncRNAs and mRNAs were screened for further Weighted Gene Co-expression Network Analysis (WGCNA). GCPM-related hub lncRNAs and genes were identified by cytoHubba and validated by Quantitative real-time PCR (qRT-PCR), Receiver operating characteristic curve (ROC) analysis and Kaplan-Meier survival analysis. GO, KEGG and GSEA showed GCPM-related pathways. Correlation analysis revealed the potential relationship between hub lncRNAs and genes.ResultsBy analyzing lncRNA expression data by WGCNA, we found that blue module was highly correlated with GCPM (r = 0.44, p = 0.04) and six lncRNAs involved in this module (DNM3OS, lnc-MFAP2-53, lnc-PPIAL4C-4, lnc-RFNG-1, lnc-TRIM28-14 and lnc-YARS2-4) were identified. We then performed qRT-PCR validation of gastric cancer specimens and found that the expression of lnc-RFNG-1 and lnc-TRIM28-14 was significantly increased in gastric cancer tissues with peritoneal metastasis. Kaplan-Meier survival analysis showed shorter overall survival time (OS) for gastric cancer patients with high expression of lnc-TRIM28-14. Receiver operating characteristic curve (ROC) analysis showed that lnc-TRIM28-14 could improve the sensitivity and specificity of GCPM diagnosis. In addition, we identified three key mRNAs (CD93, COL3A1 and COL4A1) associated with gastric cancer peritoneal metastasis through WGCNA analysis and clinical specimen validation. Moreover, there was a positive correlation between lnc-TRIM28-14 and the expression of CD93 and COL4A1 in gastric cancer peritoneal metastasis, suggesting a regulatory relationship between them. Subsequent GO, KEGG and GSEA analysis suggested that ECM-receptor interaction and focal adhesion were the hub pathways of GCPM.ConclusionIn summary, lnc-RFNG-1, lnc-TRIM28-14, CD93, COL3A1 and COL4A1 could be novel tumor biomarkers and potential therapeutic targets for GCPM.

Identification of immunocell infiltrates and effective diagnostic biomarkers in laryngeal carcinoma.

Laryngeal cancer (LC) is a malignant tumor that occurs in the head and neck. Laryngeal cancer is one of the most common cancers of the neck and head, and its prognosis has always been poor. The incidence of LC increased gradually and showed an early rising trend. Laryngeal cancer is rarely studied in relation to immunity, Malignant tumors will change the state of the human body in various ways to adapt to their own survival and avoid the immune system. This study aims to explore the immune molecular mechanism of laryngeal cancer through bioinformatics analysis. The gene expression data was downloaded for 3 microarray datasets: GSE27020, GSE59102, and GSE51985. CIBERSORT algorithm was performed to evaluate immune cell infiltration in tissues between LC and healthy control (HC). Differentially expressed genes (DEGs) were screened. Functional correlation of DEGs were analyzed by Gene Ontology, Gene Set Enrichment Analysis and Kyoto encyclopedia of genes and genomes. Candidate biomarkers were identified by cytoHubba of Cytoscape. Spearman correlations between the above biomarkers and infiltrating immune cells were explored using R software analysis. The immune cell types of LC and HC were significantly different. Twenty-one DEGs were obtained by cross-screening. The function of DEGs is closely related to the number of immune cells. Five central genes (TNNT3, TNNI2, Desmin, matrix metallopeptidase 9 and cytotoxic T lymphocyte antigen 4) were screened. The HUB gene was demonstrated to have the ability to diagnose LC and HC with good specificity and sensitivity. The correlation between immune cells and biomarkers showed that hub gene was positively correlated with macrophages and dendritic cells, and negatively correlated with CD4 + T cell. TNNT3, TNNI2, Desmin, matrix metallopeptidase 9 and cytotoxic T lymphocyte antigen 4 can be used as diagnostic biomarker for LC. Macrophages, dendritic cells and CD4 + T cell may participate in the occurrence and development of LC.

Development and validation of nomogram of peritoneal metastasis in gastric cancer based on simplified clinicopathological features and serum tumor markers

BackgroundPeritoneal metastasis (PM) is not uncommon in patients with gastric cancer(GC), which affects clinical treatment decisions, but the relevant examination measures are not efficiently detected. Our goal was to develop a clinical radiomics nomogram to better predict peritoneal metastases.MethodsA total of 3480 patients from 2 centers were divided into 1 training, 1 internal validation, and 1 external validation cohort(1949 in the internal training set, 704 in the validation set, and 827 in the external validation cohort) with clinicopathologically confirmed GC. We recruited 11 clinical factors, including age, sex, smoking status, tumor size, differentiation, Borrmann type, location, clinical T stage, and serum tumor markers (STMs) comprising carbohydrate antigen 19–9 (CA19-9), carbohydrate antigen 72–4 (CA72-4), and carcinoembryonic antigen (CEA), to develop the radiomics nomogram. For clinical predictive feature selection and the establishment of clinical models, statistical methods of analysis of variance (ANOVA), relief and recursive feature elimination (RFE) and logistic regression analysis were used. To develop combined predictive models, tumor diameter, type, and location, clinical T stage and STMs were finally selected. The discriminatory ability of the nomogram to predict PM was evaluated by the area under the receiver operating characteristic curve(AUC), and decision curve analysis (DCA) was conducted to evaluate the clinical usefulness of the nomogram.ResultsThe AUC of the clinical models was 0.762 in the training cohorts, 0.772 in the internal validation cohort, and 0.758 in the external validation cohort. However, when combined with STMs, the AUC was improved to 0.806, 0.839 and 0.801, respectively. DCA showed that the combined nomogram was of good clinical evaluation value to predict PM in GC.ConclusionsThe present study proposed a clinical nomogram with a combination of clinical risk factors and radiomics features that can potentially be applied in the individualized preoperative prediction of PM in GC patients.

Retraction Note: Superiority of [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT to [18F]FDG PET/CT in delineating the primary tumor and peritoneal metastasis in initial gastric cancer.

Retraction Note: Superiority of [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT to [18F]FDG PET/CT in delineating the primary tumor and peritoneal metastasis in initial gastric cancer.

BGN/FAP/STAT3 positive feedback loop mediated mutual interaction between tumor cells and mesothelial cells contributes to peritoneal metastasis of gastric cancer.

Peritoneal metastasis (PM) is most frequent in gastric cancer (GC) and cancer-associated fibroblasts (CAFs) play a critical role in this process. However, the concrete mechanism of crosstalk between CAFs and cancer cells in PM of GC remains unclear. Microarray sequencing of GC focus and PM lesions was performed, and biglycan (BGN) was screened for further study. Clinically, BGN expression was higher in GC tissues than adjacent normal tissues, and high expression correlated with poor prognosis. In vitro experiments demonstrated that BGN promoted tumor progression and the transformation of mesothelial cells (MCs) into cancer-associated fibroblasts like cells (CAFLCs). In turn, CAFLCs-derived fibroblast activation protein (FAP) facilitated the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of GC cells. GC-derived BGN combined with toll like receptor 2 (TLR2)/TLR4 on MCs to activate the NF-κB pathway and promote the transformation of MCs into CAFLCs by the recovery experiment, coimmunoprecipitation assay, nuclear and cytoplasmic protein extraction assay. CAFLCs-derived FAP could activate the JAK2/STAT3 signaling pathway in GC. Finally, activated STAT3 promoted BGN transcription in GC, resulting in a BGN/FAP-STAT3 positive feedback loop. Taken together, mutual interaction between tumor cells and activated MCs mediated by a BGN/FAP-STAT3 positive feedback loop facilitates PM of GC and provides a potential biomarker and therapeutic target for GC metastasis.

Retracted: Levels and Significance of Tumor Markers and Cytokines in Serum and Peritoneal Lavage Fluid of Patients with Peritoneal Metastasis of Gastric Cancer.

[This retracts the article DOI: 10.1155/2022/9528444.].

Rab27b, a Regulator of Exosome Secretion, Is Associated With Peritoneal Metastases in Gastric Cancer.

Peritoneal metastasis (PM) of gastric cancer (GC) leads to poor clinical outcomes. Tumor-derived exosomes promote metastasis via communication between tumor cells and host cells. In this study, we investigated the effect of Rab27, which is required for exosome secretion, on the PM of GC. We established a stable knockdown of two Rab27 homologs, Rab27a and Rab27b, in human GC cells (58As9) with a high potential of PM. We examined the level of exosome secretion from Rab27-knockdown 58As9 cells by Western blotting and the ability of Rab27b knockdown to suppress PM in 58As9 cells using a mouse xenograft model. In vitro proliferation and invasion assays were performed in the Rab27b-knockdown cells. Next, Rab27b expression was evaluated in human GC tissues by immunohistochemistry. Finally, we assessed the clinicopathological and prognostic significance of Rab27b expression by RT-qPCR in both our and other TCGA datasets of GC. Rab27a and Rab27b knockdown in 58As9 cells decreased the secretion of exosomes, characterized by the endocytic marker CD63. Rab27b knockdown decreased PM in vivo without affecting the in vitro proliferation or invasion ability of 58As9 cells. In human GC tissues, Rab27b was overexpressed in tumor cells. The overall and recurrence-free survival rates were significantly lower in GC patients with high compared to low Rab27b mRNA expression in our and other TCGA datasets. Rab27b expression potentially serves as a poor prognostic biomarker, possibly affecting PM via exosome secretion from GC cells.

Predictors of peritoneal metastasis of gastric origin

BackgroundGastric adenocarcinoma is one of the most aggressive forms of cancer. Despite marked advancements in radiological techniques, peritoneal deposits are still only discovered during laparotomies in a significant number of cases. The role of surgery in the management of metastatic gastric cancer is very limited, reducing the value of conducting laparotomies. In addition, conducting laparoscopies for the purposes of properly staging every case of gastric cancer is difficult, especially in healthcare systems with limited resources. It is thus crucial to investigate all possible predictors of peritoneal metastasis of gastric cancer, with the aim of reserving the use of laparoscopies to cases known to have high incidences of peritoneal metastasis despite negative radiological results.Patients and methodsThis is a case control study that included all cases of gastric adenocarcinoma that had presented to the National Cancer Institute–Cairo University between January 2018 and December 2019. The ‘cases’ group encompassed all gastric adenocarcinoma patients who were found to have peritoneal metastasis, whilst the ‘control’ group included those patients who were apparently metastasis-free. Comparisons were made between the two groups in terms of demographics, tumor characteristics, and results of laboratory tumor marker investigations.ResultsPatients with peritoneal metastasis were statistically significantly younger than those who had no apparent metastasis (mean ± SD 51.4 ± 12.5 and 56.2 ± 12.6 respectively; P = 0.020). Significant associations were found between a finding of peritoneal metastasis and (i) a middle tumor site (P = 0.002); (ii) tumor thickening morphology (P < 0.001); (iii) undifferentiated histopathology (P = 0.040); (iv) tumor grade III (P < 0.001); (v) lower lymphocyte counts of < 1.9/ml (P = 0.030); and (vi) high levels of CA 19-9 of > 37 units/ml (P = 0.032).ConclusionTumor pathological criteria, including tumor site, degree of differentiation, shape, and grading, as well as laboratory findings of low lymphocytic counts and high levels of CA 19-9 appear to be reliable predictors of the presence of peritoneal metastasis from a gastric adenocarcinoma.

LINC00924-induced fatty acid metabolic reprogramming facilitates gastric cancer peritoneal metastasis via hnRNPC-regulated alternative splicing of Mnk2

The molecular mechanism underlying gastric cancer (GC) peritoneal metastasis (PM) remains unclear. Here, we identified LINC00924 as a GC PM-related lncRNA through Microarray sequencing. LINC00924 was highly expressed in GC, and its high expression is associated with a broad range of PM. Via RNA sequencing, RNA pulldown assay, mass spectrometry, Seahorse, Lipidomics, spheroid formation and cell viability assays, we found that LINC00924 promoted fatty acid (FA) oxidation (FAO) and FA uptake, which was essential for matrix-detached GC cell survival and spheroid formation. Regarding the mechanism, LINC00924 regulated the alternative splicing (AS) of Mnk2 pre-mRNA by binding to hnRNPC. Specifically, LINC00924 enhanced the binding of hnRNPC to Mnk2 pre-mRNA at e14a, thus downregulating Mnk2a splicing and regulating the p38 MAPK/PPARα signaling pathway. Collectively, our results demonstrate that LINC00924 plays a role in promoting GC PM and could serve as a drug target.