Peritoneal Metastasis Of Gastric Cancer Research Articles

Peritoneal-directed chimeric oncolytic virus CF17 prevents malignant ascites and improves survival in gastric cancer peritoneal metastases

Gastric cancer (GC) peritoneal metastasis (PM) is fatal without effective therapy. We investigated CF17, a new replication-competent chimeric poxvirus, against GC cell lines invitro and PM in an aggressive GCPM mouse model. We performed viral proliferation and cytotoxicity assays on intestinal-type and diffuse-type human GC cell lines following CF17 treatment. At lower MOIs of 0.01, 0.1, there was >80% killing in most cell lines, while in the more aggressive cell lines, killing was seen at higher MOIs of 1.0 and 10.0. We observed reduced peritoneal tumor burden and prolonged survival with intraperitoneal (i.p.) CF17 treatment in nude mice implanted with the resistant GC cell line. At day 91 after treatment, seven of eight mice were alive in the CF17-treated group vs. one of eight mice in the control group. CF17 treatment inhibited ascites formation (0% vs. 62.5% with PBS). Thus, CF17 efficiently infected, replicated in, and killed GC cells in a dose- and time-dependent manner invitro. Invivo, i.p. CF17 treatment exhibited robust antitumor activity against an aggressive GCPM model to decrease tumor burden, improve survival, and prevent ascites formation. These preclinical results inform the design of future clinical trials of CF17 for peritoneal-directed therapy in GCPM patients.

ACLY promotes gastric tumorigenesis and accelerates peritoneal metastasis of gastric cancer regulated by HIF-1A

ABSTRACT Mounting evidence indicates the potential involvement of ATP-citrate lyase (ACLY) in the modulation of various cancer types. Nevertheless, the precise biological significance of ACLY in gastric cancer (GC) remains elusive. This study sought to elucidate the biological function of ACLY and uncover its influence on peritoneal metastasis in GC. The expression of ACLY was assessed using both real-time quantitative PCR and western blot techniques. To investigate the impact of ACLY on the proliferation of gastric cancer (GC) cells, colony formation and 5-ethynyl-2’-deoxyuridine (EdU) assays were performed. The migratory and invasive abilities of GC were evaluated using wound healing and transwell assays. Additionally, a bioinformatics analysis was employed to predict the correlation between ACLY and HIF-1A. This interaction was subsequently confirmed through a chromatin immunoprecipitation (ChIP) assay. ACLY exhibited upregulation in gastric cancer (GC) as well as in peritoneal metastasis. Its overexpression was found to facilitate the proliferation and metastasis of GC cells in both in vitro and in vivo experiments. Moreover, ACLY was observed to play a role in promoting angiogenesis and epithelial-mesenchymal transition (EMT). Notably, under hypoxic conditions, HIF-1A levels were elevated, thereby acting as a transcription factor to upregulate ACLY expression. Under the regulatory influence of HIF-1A, ACLY exerts a significant impact on the progression of gastric cancer, thereby facilitating peritoneal metastasis.

Establishment and verification of prediction model of occult peritoneal metastasis in advanced gastric cancer

BackgroundTo investigate the risk factors associated with the development of occult peritoneal metastasis in advanced gastric cancer, and establish and externally validate a nomogram for predicting the occurrence of occult peritoneal metastasis in patients with advanced gastric cancer.MethodsA total of 111 patients with advanced gastric cancer who underwent laparoscopic exploration or peritoneal lavage cytology examination at the Affiliated Drum Tower Hospital of Nanjing University Medical School from August 2014 to December 2021 were retrospectively analyzed. The patients diagnosed between 2019 and 2021 were assigned to the training set (n = 64), while those diagnosed between 2014 and 2016 constituted the external validation set (n = 47). In the training set, patients were classified into two groups based on preoperative imaging and postoperative pathological data: the occult peritoneal metastasis group (OPMG) and the peritoneal metastasis negative group (PMNG). In the validation set, patients were classified into the occult peritoneal metastasis group (CY1P0, OPMG) and the peritoneal metastasis negative group (CY0P0, PMNG) based on peritoneal lavage cytology results. A nomogram was constructed using univariate and multivariate analyses. The performance of the nomogram was evaluated using Harrell’s C-index, the area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and calibration plots.ResultsThis study analyzed 22 potential variables of OPM in 111 gastric cancer patients who underwent laparoscopic exploration or peritoneal lavage cytology examination. Logistic regression analysis results showed that Lauren classification, CLDN18.2 score and CA125 were independent risk factors for OPM in patients with gastric cancer. We developed a simple and easy-to-use prediction nomogram of occult peritoneal metastasis in advanced gastric cancer. This nomogram had an excellent diagnostic performance. The AUC of the bootstrap model in the training set was 0.771 and in the validation set was 0.711. This model showed a good fitting and calibration and positive net benefits in decision curve analysis. ConclusionWe have developed a prediction nomogram of OPM for gastric cancer. This novel nomogram has the potential to enhance diagnostic accuracy for occult peritoneal metastasis in gastric cancer patients.

Galectin-3 Cooperates with CD47 to Suppress Phagocytosis and T-cell Immunity in Gastric Cancer Peritoneal Metastases.

Dual inhibition of CD47 and Gal3 enhances tumor cell phagocytosis and reprograms macrophages to overcome the immunosuppressive microenvironment and suppress tumor growth in peritoneal metastasis of gastric adenocarcinoma.

The Role of Additional Staining in the Assessment of the Peritoneal Regression Grading Score (PRGS) in Peritoneal Metastasis of Gastric Origin.

The Peritoneal Regression Grading Score (PRGS) is a 4-tied histologic regression grading score for determining the response of peritoneal metastasis to chemotherapy. Peritoneal biopsies in every abdominal quadrant are recommended. A positive therapy response is defined as a decreasing or stable mean PRGS between 2 therapy cycles. The added value of periodic acid satin (PAS) and Ber-EP4 staining over HE staining for diagnosing PRGS1 (the absence of vital tumor cells) is unclear. A total of 339 biopsies obtained during 76 laparoscopies in 33 patients with peritoneal metastasis of gastric cancer were analyzed. Biopsies classified as PRGS 1 (no residual tumor, n=95) or indefinite (n=50) were stained with PAS, and remaining indefinite or PRGS1 cases additionally stained with BerEP4. After PAS-staining tumor cells were detected in 28 out of 145 biopsies (19%), the remaining 117 biopsies were immunostained with Ber-EP4. Tumor cells were detected in 22 biopsies (19%). In total, additional staining allowed the detection of residual tumor cells in 50 out of 339 biopsies (15%) and changed the therapy response assessment in 7 out of 33 (21%) patients. In summary, 25% (24 out of 95) of initially tumor-free samples (PRGS1) showed residual tumor cells after additional staining with PAS and/or BerEp4. Immunohistochemistry provided important additional information (the presence of tumor cells) in 22 of all 339 biopsies (11.2%). Further staining reduced the instances of unclear diagnosis from 50 to 0 and changed the therapy response assessment in 7 out of 33 patients (21%). We recommend additional staining in PRGS1 or unclear cases.

Clinical effectiveness of fluorouracil and cisplatin intraperitoneal perfusion combined with intravenous chemotherapy for peritoneal metastasis in gastric cancer.

Gastric cancer (GC) is one of the most common malignancies worldwide, often accompanied by peritoneal metastasis. This work aimed to investigate the clinical efficacy of intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy for the treatment of peritoneal metastasis in GC. A total of 286 patients with primary GC admitted to the hospital from March 2017 to December 2020 were recruited in the study. A 1:1 matched case-control study was conducted, with the normal control (NC) group and experimental (E) group being composed of patients who underwent the corresponding treatment for primary GC with surgery within 2 months and the same pathological tumor-node-metastasis (pTNM) stage. The NC group consisted of 143 patients receiving only intravenous chemotherapy, while the E group consisted of 143 patients receiving intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy. Baseline characteristics, clinical efficacy, complications, peritoneal recurrence and metastasis, disease-free survival (DFS), and overall survival (OS) of the patients, as well as their quality of life (QoL) after chemotherapy, were compared between groups. After six cycles of chemotherapy, DFS was observed in both groups (70% vs. 59%; 48% vs. 29.7%; p<0.05), so did OS (85.7% vs. 85.4%; 73.1% vs. 69.3%; p>0.05). The total effective rate of treatment in the E group (46.15%) was drastically superior to that in the NC group (27.97%), and the total recurrence and metastasis rate of the E group (23.08%) was markedly inferior to that of the NC group (83.9%) (p<0.05). The total incidence of adverse reactions in the E group (11.89%) was considerably inferior to that in the NC group (35.66%) (p<0.05). In addition, the E group had markedly superior scores for physical function (PF), emotional function (EF), role function (RF), social function (SF), and cognitive function (CF) than the NC group (p<0.05). Intraperitoneal perfusion of fluorouracil and cisplatin combined with intravenous chemotherapy for the treatment of peritoneal metastasis in GC had certain benefits for patients and is worth applying in clinical practice.

Chinese expert consensus on the diagnosis and treatment of peritoneal metastasis of gastric cancer (2023 edition)

China is a country with a high incidence of gastric cancer, and the majority of patients are in the advanced stage. The peritoneum is the most common site of metastasis and recurrence in advanced gastric cancer. Attention to the standardized diagnosis and treatment of peritoneal metastases of gastric cancer is expected to significantly improve the prognosis and quality of life of some patients. Based on evidence-based medicine and the internationally accepted Delphi method, this consensus revises the Chinese expert consensus on the prevention and treatment of peritoneal metastasis of gastric cancer (2017 edition), reaches a preliminary consensus on the definition, classification, risk factors, diagnosis and prediction, grade assessment, prevention, treatment and management of complications of peritoneal metastasis of gastric cancer, and provides guidance for clinical work.

Gastric cancer peritoneal metastasis related signature predicts prognosis and sensitivity to immunotherapy in gastric cancer.

Gastric cancer peritoneal metastases (GCPM) is a leading cause of GC-related death. Early detection of GCPM is critical for improving the prognosis of advanced GC. Differentially expressed genes (DEGs) were identified in the GSE62254 database to distinguish between GCPM and non-GCPM. The gastric cancer peritoneal metastases signature (GCPMs) was developed using DEGs. We analysed the effectiveness of GCPMs as indicators for prognosis, chemotherapy, and immune therapy response in GC patients. Subsequently, we analysed the correlation between GCPMs and immune microenvironment as well as immune escape in GC patients. Random forest model and immunohistochemistry was utilized to identify the crucial genes that can aid in the diagnosis of GCPM. We identified five DEGs and utilized their expression to construct GCPMs. Patients with high GCPMs had a higher likelihood of a poor prognosis, while those with low GCPMs appeared to potentially benefit more from chemotherapy. GCPMs were a dependable marker for predicting the response to immunotherapy. Additionally, GCPMs was found to be significantly linked to stromal score and cancer-associated fibroblasts. SYNPO2 has been identified as the gene with the highest significance in the diagnosis of GCPM. Immunohistochemistry suggests that SYNPO2-positive expression in tumour cells, fibroblasts, inflammatory cell may be associated with promoting peritoneal metastasis in GC. GCPMs have shown to be a promising biomarker for predicting the prognosis and response of GC patients to chemotherapy and immunotherapy. The use of GCPMs for individual tumour evaluation may pave the way for personalized treatment for GC patients in the future.

A radiomics nomogram based on 18 F-FDG PET/CT and clinical risk factors for the prediction of peritoneal metastasis in gastric cancer.

Peritoneal metastasis (PM) is usually considered an incurable factor of gastric cancer (GC) and not fit for surgery. The aim of this study is to develop and validate an 18 F-FDG PET/CT-derived radiomics model combining with clinical risk factors for predicting PM of GC. In this retrospective study, 410 GC patients (PM - = 281, PM + = 129) who underwent preoperative 18 F-FDG PET/CT images from January 2015 to October 2021 were analyzed. The patients were randomly divided into a training cohort (n = 288) and a validation cohort (n = 122). The maximum relevance and minimum redundancy (mRMR) and the least shrinkage and selection operator method were applied to select feature. Multivariable logistic regression analysis was preformed to develop the predicting model. Discrimination, calibration, and clinical usefulness were used to evaluate the performance of the nomogram. Fourteen radiomics feature parameters were selected to construct radiomics model. The area under the curve (AUC) of the radiomics model were 0.86 [95% confidence interval (CI), 0.81-0.90] in the training cohort and 0.85 (95% CI, 0.78-0.92) in the validation cohort. After multivariable logistic regression, peritoneal effusion, mean standardized uptake value (SUVmean), carbohydrate antigen 125 (CA125) and radiomics signature showed statistically significant differences between different PM status patients( P < 0.05). They were chosen to construct the comprehensive predicting model which showed a performance with an AUC of 0.92 (95% CI, 0.89-0.95) in the training cohort and 0.92 (95% CI, 0.86-0.98) in the validation cohort, respectively. The nomogram based on 18 F-FDG PET/CT radiomics features and clinical risk factors can be potentially applied in individualized treatment strategy-making for GC patients before the surgery.

ASO Visual Abstract: Bidirectional Approach with PIPAC and Systemic Chemotherapy for Patients with Synchronous Gastric Cancer Peritoneal Metastases (GCPM).

ASO Visual Abstract: Bidirectional Approach with PIPAC and Systemic Chemotherapy for Patients with Synchronous Gastric Cancer Peritoneal Metastases (GCPM).

Clinical significance of intraperitoneal paclitaxel combined with systemic chemotherapy for gastric cancer with peritoneal metastasis.

Despite investigations of intraperitoneal paclitaxel as a personalized treatment for peritoneal metastasis of gastric cancer, few studies have evaluated its prognostic impact on conversion surgery for unresectable gastric cancer with peritoneal metastasis. Our study aimed to close this gap in knowledge. We retrospectively enrolled 128 patients who underwent chemotherapy for peritoneal metastasis from gastric cancer and assigned them into intraperitoneal (IP) (n = 36) and non-IP (n = 92) groups, based on the use of intraperitoneal paclitaxel plus systemic chemotherapy. Disease control rates were 94% and 69% in the IP and non-IP groups, respectively, with the former having a significantly higher tumor response rate than the latter (p < 0.01). The median survival times in the IP and non-IP groups were 665 and 359days, respectively, with the former having significantly better prognosis than the latter (p = 0.02). Fifteen (42%) and sixteen (17%) patients underwent conversion surgery after chemotherapy in the IP and non-IP groups, respectively, with the former having a significantly higher conversion surgery induction rate than the latter (p < 0.01). Although the prognosis of the conversion surgery group was significantly better than that of the non-conversion surgery group (p < 0.01), there was no significant difference in prognosis between patients in the IP and non-IP groups who underwent conversion surgery (p = 0.22). Multivariate analysis identified performance status and conversion surgery as independent prognostic factors (all p < 0.01). Our study demonstrated that the IP chemotherapy was one of important factors for conversion surgery induction, while it was not a risk factor for prognosis.

Liquid tumor microenvironment enhances WNT signaling pathway of peritoneal metastasis of gastric cancer

Gastric cancer remains one of the most prevalent tumors worldwide and peritoneal metastasis is responsible for approximately 60% of death in advanced gastric cancer patients. However, the underlying mechanism of peritoneal metastasis is poorly understood. We have established organoids derived from malignant ascites (MA) of gastric cancer patients and noticed that MA supernatant could strongly increase the colony formation of organoids. Thus, we realized the interaction between exfoliated cancer cells (ECCs) and liquid tumor microenvironment contributes to peritoneal metastasis. Further, we designed a medium component control test which proved that exosomes derived from MA could not enhance the growth of organoids. Using Immunofluorescence and confocal imaging as well as dual-luciferase reporter assay, our data showed WNT signaling pathway was upregulated by high concentrations of WNT ligands (wnt3a and wnt5a), which was verified by ELISA. Besides, suppressing WNT signaling pathway diminished the growth promoting function of MA supernatant. This result implicated WNT signaling pathway as a potential therapeutic target for peritoneal metastasis of gastric cancer.

Prediction of occult peritoneal metastases or positive cytology using CT in gastric cancer.

Accurate prediction of preoperative occult peritoneal metastasis (OPM) is critical to selecting appropriate therapeutic regimen for gastric cancer (GC). Considering the clinical practicability, we develop and validate a visible nomogram that integrates the CT images and clinicopathological parameters for the individual preoperative prediction of OPM in GC. This retrospective study included 520 patients who underwent staged laparoscopic exploration or peritoneal lavage cytology (PLC) examination. Univariate and multivariate logistic regression results were used to screen model predictors and construct nomograms of OPM risk. The performance of the model was detected by using ROC, accuracy, and C-index. The bootstrap resampling method was considered internal validation of the model. The Delong test was used to evaluate the difference in AUC between the two models. Grade 2 mural stratification, tumor thickness, and the Lauren classification diffuse were significant predictors of OPM (p < 0.05). The nomogram of these three factors (compared with the original model) showed a higher predictive effect (p < 0.001). The area under the curve (AUC) of the model was 0.830 (95% CI 0.788-0.873), and the internally validated AUC of 1000 bootstrap samples was 0.826 (95% CI 0.756-0.870). The sensitivity, specificity, and accuracy were 76.0%, 78.8%, and 78.3%, respectively. CT phenotype-based nomogram demonstrates favorable discrimination and calibration, and it can be conveniently used for preoperative individual risk rating of OPM in GC. In this study, the preoperative OPM prediction model based on CT images (mural stratification, tumor thickness) combined with pathological parameters (the Lauren classification) showed excellent predictive ability in GC, and it is also suitable for clinicians to use rather than limited to professional radiologists. • Nomogram based on CT image analysis can effectively predict occult peritoneal metastasis in gastric cancer (training area under the curve (AUC) = 0.830 and bootstrap AUC = 0.826). • Nomogram model combined with CT features performed better than the original model (established using only clinicopathological parameters) in differentiating occult peritoneal metastasis of gastric cancer.

Therapeutic effects and safety of apatinib mesylate on patients with gastric carcinoma peritoneal metastasis in SOX scheme.

The aim of this study was to investigate the diagnostic values of serum tumor markers in gastric carcinoma peritoneal metastasis and the therapeutic efficacy as well as safety of apatinib mesylate combined with Geo+Oxaliplatin (SOX) scheme treatment in gastric carcinoma peritoneal metastasis. Sixty patients with gastric carcinoma peritoneal metastasis and 11 patients without gastric carcinoma peritoneal metastasis were selected as the research subjects. The levels of serum tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9] and abdominal irrigating solution exosome [micro ribonucleic acid (miR)-21 and miR-320c] and the differences in their diagnostic values were compared and analyzed. The patients with gastric cancer peritoneal metastases are then divided into two groups, one for control (30 cases receiving just SOX scheme treatment) and the other for the experiment (30 cases receiving SOX scheme treatment plus apatinib mesylate). Besides, the differences in serum tumor marker level, therapeutic efficacy, overall survival (OS), complication rating, and Quality of Life Questionnaire-Core-30 (QLQ-C30) score among patients after treatment were compared. Demonstrated that serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 125, CA211, CA242, CA724, and CA19-9 levels of patients in the transfer group were remarkably enhanced compared with those of patients in the non-transfer group, and the levels of abdominal irrigating solution exosome (miR-21 and miR-320c) were reduced compared with those in non-transfer group (p<0.05). The area under the curve (AUC) of the diagnosis of gastric carcinoma peritoneal metastasis by each index were 0.553, 0.880, 0.832, 0.619, 0.863, 0.651, 0.918, and 0.903, respectively. Patients in the experimental group's serum levels of CEA, CA125, CA211, CA242, CA724, and CA19-9 were noticeably lower after therapy compared to those in the control group, and their median OS was also noticeably longer (p<0.05). After treatment, the objective remission rate (ORR) and disease control rate (DCR) of the control group and experimental group amounted to 6.7% vs. 30.0% and 50.0% vs. 86.7%, respectively. ORR and DCR of the experimental group were notably higher (p<0.05). Between the patients in the control group and the experimental group, there were no glaring variations in the frequency of problems (hypertension, nausea, vomiting, bone marrow suppression, hand-foot syndrome, and leucopenia) (p>0.05). The cognitive function, emotional function, and life health scores of patients in the experimental group were significantly higher than those in the control group (p<0.05), which suggested that serum tumor markers and miR-21 as well as miR-320c showed high diagnostic efficiency in gastric carcinoma peritoneal metastasis. Apatinib mesylate combined with SOX scheme treatment was more effective in treating gastric carcinoma peritoneal metastasis and possessed the same safety as single SOX scheme treatment. Hence, it is worthy of clinical promotion.

Galectin-1 promotes gastric cancer peritoneal metastasis through peritoneal fibrosis

BackgroundPeritoneal metastasis is one of the main causes of death in patients with gastric cancer (GC). Galectin-1 regulates various undesirable biological behaviors in GC and may be key in GC peritoneal metastasis.MethodsIn this study, we elucidated the regulatory role of galectin-1 in GC cell peritoneal metastasis. GC and peritoneal tissues underwent hematoxylin–eosin (HE), immunohistochemical (IHC), and Masson trichrome staining to analyze the difference in galectin-1 expression and peritoneal collagen deposition in different GC clinical stages. The regulatory role of galectin-1 in GC cell adhesion to mesenchymal cells and in collagen expression was determined using HMrSV5 human peritoneal mesothelial cells (HPMCs). Collagen and corresponding mRNA expression were detected with western blotting and reverse transcription PCR, respectively. The promoting effect of galectin-1 on GC peritoneal metastasis was verified in vivo. Collagen deposition and collagen I, collagen III, and fibronectin 1 (FN1) expression in the peritoneum of the animal models were detected by Masson trichrome and IHC staining.ResultsGalectin-1 and collagen deposition in the peritoneal tissues was correlated with GC clinical staging and were positively correlated. Galectin-1 enhanced the ability of GC cells to adhere to the HMrSV5 cells by promoting collagen I, collagen III, and FN1 expression. The in vivo experiments confirmed that galectin-1 promoted GC peritoneal metastasis by promoting peritoneal collagen deposition.ConclusionGalectin-1-induced peritoneal fibrosis may create a favorable environment for GC cell peritoneal metastasis.

Bidirectional Approach with PIPAC and Systemic Chemotherapy for Patients with Synchronous Gastric Cancer Peritoneal Metastases (GCPM)

BackgroundThis study evaluated the efficacy of pressurized intraperitoneal aerosol chemotherapy (PIPAC) with systemic chemotherapy as a bidirectional approach for gastric cancer (GC) patients with synchronous peritoneal metastases (SPM).MethodsA retrospective analysis of a prospective PIPAC database was queried for patients who underwent a bidirectional approach between October 2019 and April 2022 at two high-volume GC surgery units in Italy (Verona and Siena). Surgical and oncological outcomes were analyzed.ResultsBetween October 2019 and April 2022, 74 PIPAC procedures in 42 consecutive patients with Eastern Cooperative Oncology Group performance status ≤2 were performed—32 patients treated in Verona and 10 in Siena. Twenty-seven patients (64%) were female and median age at first PIPAC was 60.5 years (I–III quartiles: 49–68 years). Median Peritoneal Cancer Index (PCI) was 16 (I–III quartiles: 8–26) and 25 patients (59%) had at least two PIPAC procedures. Major complications according to the Common Terminology Criteria for Adverse Events (CTCAE; 3 and 4) occurred in three (4%) procedures, and, according to the Clavien–Dindo classification (>3a), one (1%) severe complication occurred. There were no reoperations or deaths within 30 days. Median overall survival (mOS) from diagnosis was 19.6 months (range 14–24), and mOS from first PIPAC was 10.5 months (range 7–13). Excluding cases with very heavy metastatic peritoneal burden, with PCI from 2 to 26, treated with more than one PIPAC, mOS from diagnosis was 22 months (range 14–39). Eleven patients (26%) underwent curative-intent surgery after a bidirectional approach. R0 was achieved in nine (82%) patients and complete pathological response was obtained in three (27%) cases.ConclusionsPatient selection is associated with bidirectional approach efficacy and feasibility for SPM GC treatment, which may allow potentially curative surgical radicalization in highly selected cases.

Towards an optimal model for gastric cancer peritoneal metastasis: current challenges and future directions.

Peritoneal metastasis is a challenging aspect of clinical practice for gastric cancer. Animal models are crucial in understanding molecular mechanisms, assessing drug efficacy, and conducting clinical intervention studies, including those related to gastric cancer peritoneal metastasis. Unlike other xenograft models, peritoneal metastasis models should not only present tumor growth at the transplant site, but also recapitulate tumor cell metastasis in the abdominal cavity. Developing a reliable model of gastric cancer peritoneal metastasis involves several technical aspects, such as the selection of model animals, source of xenograft tumors, technology of transplantation, and dynamic monitoring of the tumor progression. To date, challenges remain in developing a reliable model that can completely recapitulate peritoneal metastasis. Thus, this review aims to summarize the techniques and strategies used to establish animal models of gastric cancer peritoneal metastasis, providing a reference for future model establishment.

CD44-positive Cancer Stem-like Cells as a Potential Source of Peritoneal Metastasis After Surgery.

The role of CD44 in gastric cancer-derived peritoneal metastasis is currently unknown. It was previously shown that viable, tumorigenic cancer cells are spilled into the peritoneal cavity during surgery, providing a potential cause of peritoneal recurrence after surgery. The purpose of this study was to elucidate the mechanism of peritoneal metastasis of gastric cancer through the expression of CD44 and to propose a method for preventing peritoneal recurrence. Gastric cancer cell line MKN-45 was sorted into CD44+ and CD44- cells and then injected intraperitoneally into NOD/ShiJic-scidJcl mice. Differences in tumor-initiating capacity between the two groups were assessed using in vivo limiting dilution assays. Tumors harvested from both groups were examined for CD44 and ALDH1A1 expression using immunohistochemistry. The effects of CD44 blockade with anti-CD44 antibody on cell invasion and peritoneal metastasis formation in vivo were assessed. CD44+ cells showed significantly higher efficiency in initiating peritoneal tumor than CD44- cells. Blockade of CD44 significantly reduced peritoneal dissemination of CD44+ cells in vivo, indicating that the CD44 function of intraperitoneally disseminated cancer cells helped promote the formation of peritoneal metastasis. The margin of established tumors showed clusters of cells co-expressing CD44 and ALDH1A1. Peritoneally administered CD44- cells resulted in peritoneal metastases consisting of CD44+ and CD44- cancer cells. CD44 expressing cells are a potential source of peritoneal metastasis after surgery and could be a promising target for preventing peritoneal recurrence.

Single-cell RNA sequencing reveals the lineage of malignant epithelial cells and upregulation of TAGLN2 promotes peritoneal metastasis in gastric cancer.

Peritoneal metastasis (PM) is an important factor contributing to poor prognosis in patients with gastric cancer (GC). Transcriptomic sequencing has been used to explore the molecular changes in metastatic cancers, but comparing the bulk RNA-sequencing data between primary tumors and metastases in PM studies is unreasonable due to the small proportion of tumor cells in PM tissues. We performed single-cell RNA-sequencing analysis on four gastric adenocarcinoma specimens, including one primary tumor sample (PT), one adjacent nontumoral sample (PN), one peritoneal metastatic sample (MT) and one normal peritoneum sample (MN), from the same patient. Pseudotime trajectory analysis was used to display the process by which nonmalignant epithelial cells transform into tumor cells and then metastasize to the peritoneum. Finally, in vitro and in vivo assays were used to validate one of the selected genes that promote peritoneal metastasis. Single-cell RNA sequencing showed that a development curve was found from normal mucosa to tumor tissues and then into metastatic sites on peritoneum. TAGLN2 was found to trigger this metastasis process. The migration and invasion capability of GC cells were changed by downregulating and upregulating TAGLN2 expression. Mechanistically, TAGLN2 might modulate tumor metastasis via alterations in cell morphology and several signaling pathways, thus promoting epithelial-mesenchymal transition (EMT). In summary, we identified and validated TAGLN2 as a novel gene involved in GC peritoneal metastasis. This study provided valuable insight into the mechanisms of GC metastasis and developed a potential therapeutic target to prevent GC cell dissemination.

Diagnostic methods for peritoneal molecular residual disease in gastric cancer

Peritoneal metastasis of gastric cancer serving as the most frequent form of metastasis, is one of the leading causes of death. A portion of surgically treated patients often suffer from small peritoneal residual metastasis, which will lead to recurrence and metastasis of gastric cancer patients after surgery. Given these, the prevention and treatment of peritoneal metastasis of gastric cancer deserves more attention. Molecular residual disease (MRD) refers to the molecular abnormalities of tumor origin that cannot be found by traditional imaging or other laboratory methods after treatment, but can be found by liquid biopsy, representing the possibility of tumor persistence or clinical progress. In recent years, the detection of MRD based on ctDNA has gradually become a research hotspot in the prevention and treatment of peritoneal metastasis. Our team established a new method for MRD molecular diagnosis of gastric cancer, and reviewed the research achievements in this field.