Gastric Cancer Metastasis Research Articles

LncRNA PCED1B-AS1 mediates miR-3681-3p/MAP2K7 axis to promote metastasis, invasion and EMT in gastric cancer

BackgroundLncRNA PCED1B-AS1 is abnormally expressed in multiple cancers and has been confirmed as an oncogene. Our study aimed to investigate the regulatory mechanism of lncRNA PCED1B-AS1 in gastric cancer.MethodsTCGA database was used to analyze the abnormal expression of lncRNA PCED1B-AS1 in gastric cancer. By database prediction and mass spectrometric analysis, miR-3681-3p and MAP2K7 are potential downstream target molecules of lncRNA PCED1B-AS1 and verified by dual-luciferase report assay. RT-qPCR analysis and western blot were performed to detect the expressions of PCED1B-AS1 and MAP2K7 in gastric cancer cell lines and tissues. CCK-8 kit was applied to measure the cell viability. Wound healing and Transwell experiment were used to detect the migration and invasion. Western blot and immunohistochemical staining were performed to detect the expressions of EMT-related proteins in tissues. The changes of tumor proliferation were detected by xenograft experiment in nude mice.ResultsPCED1B-AS1 expression was higher but miR-3681-3 expression was lower in gastric cancer cell lines or tissues, compared to normal group. Function analysis verified PCED1B-AS1 promoted cell proliferation and inhibited cell apoptosis in gastric cancer cells in vitro and in vivo. LncRNA PCED1B-AS1 could bind directly to miR-3681-3p, and MAP2K7 was found to be a downstream target of miR-3681-3p. MiR-3681-3p mimics or si-MAP2K7 could partly reverse the effect of PCED1B-AS1 on gastric cancer cells.ConclusionPCED1B-AS1 accelerated cell proliferation and inhibited cell apoptosis through sponging miR-3681-3p to upregulate MAP2K7 expression in gastric cancer, which indicated PCED1B-AS1/miR-3681-3p/MAP2K7 axis may serve as a potential therapeutic target for gastric cancer.

Retraction: lncRNA HOTAIR promotes gastric cancer proliferation and metastasis via targeting miR-126 to active CXCR4 and RhoA signaling pathway.

Retraction: Jun Xiao, Hao Lai, Sheng-Hong Wei, Zai-Sheng Ye, Fu-Sheng Gong, Lu-Chuan Chen (2019), lncRNA HOTAIR promotes gastric cancer proliferation and metastasis via targeting miR-126 to active CXCR4 and RhoA signaling pathway. Cancer Med, 8: 6768-6779. https://doi.org/10.1002/cam4.1302 The above article, published online on 13 September 2019, and a corresponding Corrigendum (https://doi.org/10.1002/cam4.4435), published online on 22 November 2021, in Wiley Online Library (wileyonlinelibrary.com) have been retracted by agreement between the journal's Editor-in-Chief, Stephen Tait, and John Wiley & Sons Ltd. Following publication, concerns were raised by a third party regarding duplication of images included within Figures3C and 5E. Furthermore, these figures have previously been published elsewhere, identifying the cells as originating from different cell lines and subjected to different treatment. The authors did not respond to the concerns raised and did not provide the original data. The editors consider the results and conclusion reported in this article unreliable.

Risk Factors for Lymph Node Metastasis in a Western Series of Patients with Distal Early Gastric Cancer.

Background: Assessment of potential lymph node metastasis is mandatory in the appropriate treatment of early gastric cancers. This study analysed factors associated with lymph node metastasis to identify differences between node-negative and node-positive patients and between T1a and T1b cancers. Methods: The clinicopathological features of 129 early gastric cancer patients who had undergone radical gastrectomy were analysed to identify predictive factors for lymph node metastasis. Results: Lymph node metastasis was detected in 76 (59.0%) patients. Node-positive patients were younger (58.1 ± 11.3 years) than those without metastasis (61.9 ± 9.6 years, p = 0.02). Greater tumour sizes were observed in patients with lymph node metastasis (3.6 ± 1.0 cm) compared to node-negative patients (1.9 ± 0.5 cm, p = 0.00001). Depressed form, ulceration, diffuse histological type, and undifferentiated lesions were more frequent in node-positive patients than in the node-negative group. Tumour size > 3.0 cm showed a correlation with lymph node metastasis in both T1a (p = 0.0001) and T1b (p = 0.006) cancer. The male sex (p = 0.006) had a significant correlation with lymph node metastasis in T1a cancer. Depressed appearance (p = 0.02), ulceration (p = 0.03), differentiation (p = 0.0001), diffuse type (p = 0.0002), and lower third location (p = 0.005) were associated with lymph node metastasis in T1b cancer. Conclusions: Tumour size > 3 cm, undifferentiated lesions, ulceration, diffuse type, lower third location, and submucosal invasion are risk factors for lymph node metastasis in early gastric cancer.

Preoperative Risk Stratification for Gastric Cancer: The Establishment of Dual-Energy CT-Based Radiomics Using Prospective Datasets at Two Centers

ObjectiveTo evaluate the performance of dual-energy CT (DECT)-based radiomics models for identifying high-risk histopathologic phenotypes - serosal invasion (pT4a), lymph node metastasis (LNM), lymphovascular invasion (LVI) and perineural invasion (PNI) in gastric cancer. Material and MethodsThis prospective bi-center study recruited histologically confirmed gastric adenocarcinoma patients who underwent triple-phase enhanced DECT before gastrectomy between January 2021 and July 2023. Radiomics features were extracted from polychromatic/monochromatic (40keV, 100 keV)/iodine images at arterial/venous/delay phase, respectively. Predictive features were selected in the training dataset using logistic regression classifier, and trained models were applied to the external validation dataset. Performances of clinical models, conventional contrast enhanced CT (CECT) models and DECT models were evaluated using areas under the receiver operating characteristic curve (AUCs). ResultsIn total, 503 patients were recruited: 396 at training dataset (60.1 ± 10.8 years, 110 females, 286 males) and 107 at validation dataset (61.4 ± 9.5 years, 29 females, 78 males). DECT models dichotomizing pT4a, LNM, LVI, and PNI achieved AUCs of 0.891, 0.817, 0.834, and 0.889, respectively, in the validation dataset, similar with the CECT models. In the training dataset, compared with the CECT model, the DECT model provided increased performance for identifying pT4a, LNM, LVI (all P＜0.05), and similar performance for stratifying PNI (P = 0.104). The DECT models was associated with patient disease-free survival (all P ＜0.05). ConclusionDECT radiomics can stratify patients preoperatively according to high-risk histopathologic phenotypes for gastric cancer and are associated with patient disease-free survival in the training dataset.

Conversion surgery for gastric remnant cancer with liver metastasis after nivolumab combination chemotherapy achieving pathological complete response: a case report and literature review.

Nivolumab combination chemotherapy has recently emerged as a potential first-line treatment for patients with unresectable or metastatic gastric cancer (GC). Further research has indicated that R0 resection by conversion surgery could be an effective treatment strategy to improve overall survival. However, there have been limited reports on the successful application of conversion surgery following combination chemotherapy achieving pathological complete response (pCR) in cases of advanced gastric remnant cancer with liver metastasis. Here, we present a case of long-term survival in a patient who underwent this treatment. A 54-year-old man was initially referred to our department for treatment of stage III (cT3N1M0) gastric cancer where he underwent laparoscopic distal gastrectomy and D2 lymph node dissection. After a year of uneventful follow-up, the patient was diagnosed with a tumor in the gastric remnant combined with liver metastasis, resulting in a diagnosis of stage IV (cT3N0M1) gastric remnant cancer. Subsequently, the patient was treated with four cycles of TS-1, Oxaliplatin, and Nivolumab as the first-line regimen. Remarkably, both the remnant tumor and liver metastasis exhibited significant shrinkage, and no new lesions were found. Given this response, conversion surgery was performed to achieve complete resection of the remnant gastric cancer and liver metastasis, followed by laparoscopic remnant gastrectomy and partial hepatectomy. Pathological examination revealed the absence of residual carcinoma cells and lymph node metastases. Postoperatively, the patient was treated with adjuvant chemotherapy with S-1 for 1 year, and survived without recurrence for 18months after conversion surgery. Nivolumab combination chemotherapy shows promise as a clinically beneficial treatment approach for gastric remnant cancer with liver metastasis, particularly when pCR can be achieved following conversion surgery.

IGFBP7 promotes gastric cancer by facilitating epithelial-mesenchymal transition of gastric cells

Gastric cancer (GC) with high morbidity and mortality is one major cause of tumor-related death. Mechanisms underlying GC invasion and metastasis remain unclear. IGFBP7 exerted variable effects in different cancers and its role in GC is controversial. Here, IGFBP7 was found to be upregulated and elevated IGFBP7 expression represented a poorer overall survival in GC using bioinformatics analysis. Moreover, IGFBP7 was up-regulated in human GC specimens and promoted tumor growth in xenograft tumor animals. For GC cell lines, we found that IGFBP7 was also upregulated and facilitated the cell malignant behavior and EMT of GC cells, which may involve NF-κB and ERK signaling pathways. This research may provide new avenues for GC therapy.

Dynamic change in the peritoneal cancer index based on CT after chemotherapy in the overall survival prediction of gastric cancer patients with peritoneal metastasis

PurposeThe purpose of this research was to investigate the efficacy of the CT-based peritoneal cancer index (PCI) to predict the overall survival of patients with peritoneal metastasis in gastric cancer (GCPM) after two cycles of chemotherapy.MethodsThis retrospective study registered 112 individuals with peritoneal metastasis in gastric cancer in our hospital. Abdominal and pelvic enhanced CT before and after chemotherapy was independently analyzed by two radiologists. The PCI of peritoneal metastasis in gastric cancer was evaluated according to the Sugarbaker classification, considering the size and distribution of the lesions using CT. Then we evaluated the prognostic performance of PCI based on CT, clinical characteristics, and imaging findings for survival analysis using multivariate Cox proportional hazard regression.ResultsThe PCI change ratio based on CT after treatment (ΔPCI), therapy lines, and change in grade of ascites were independent factors that were associated with overall survival (OS). The area under the curve (AUC) value of ΔPCI for predicting OS with 0.773 was higher than that of RECIST 1.1 with 0.661 (P < 0.05). Patients with ΔPCI less than −15% had significantly longer OS.ConclusionCT analysis after chemotherapy could predict OS in patients with GCPM. The CT-PCI change ratio could contribute to the determination of an appropriate strategy for gastric cancer patients with peritoneal metastasis.

Exploring new frontiers: cell surface vimentin as an emerging marker for circulating tumor cells and a promising therapeutic target in advanced gastric Cancer

BackgroundCirculating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods.MethodsTo bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV+CTCs formation, a combination of Tandem Mass Tag (TMT) quantitative proteomics, m6A RNA immunoprecipitation–qPCR (MeRIP–qPCR), single-base elongation- and ligation-based qPCR amplification method (SELECT) and RNA sequencing (RNA-seq) were utilized to screen and confirm the potential target gene. Both in vitro and in vivo experiments were performed to explore the molecular mechanism of CSV expression regulation and its role in GC metastasis.ResultsOur findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV+CTCs formation, and its impact on the insulin-like growth factor-I receptor (IGF-IR) mRNA decay through m6A modification. The activation of IGF-I/IGF-IR signaling enhanced the translocation of vimentin from the cytoplasm to the cell surface through phosphorylation of vimentin at serine 39 (S39). In a GC mouse model, the simultaneous inhibition of CSV and blockade of the IGF-IR pathway yielded promising outcomes.ConclusionIn summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine.

Biological functions of Circular RNA_LARP4/ Upstream frameshift 1 in development of gastric cancer.

Recently, the progression of gastric cancer (GC), as one of the most ordinary malignant tumors, has been reported to be associated with circular RNAs. This study aimed to identify the role of circular RNA_LARP4 in GC. We performed real-time quantitative polymerase chain reaction (RT-qPCR) in 46 paired GC patients and GC cell lines to detect the expression of circular RNA_LARP4. Moreover, the role of circular RNA_LARP4 in GC proliferation was identified through proliferation assay and colony formation assay, while the role of circular RNA_LARP4 in GC metastasis was measured through scratch wound assay and transwell assay. Furthermore, the potential targets of circular RNA_LARP4 were predicted through bioinformatics methods and further identified by western blot assay and RT-qPCR. Circular RNA_LARP4 expression was remarkably lower in GC tissues compared with that in adjacent samples. Besides, cell proliferation of GC was inhibited after overexpression of circular RNA_LARP4, while cell migration and invasion of GC was inhibited after overexpression of circular RNA_LARP4. Furthermore, Upstream frameshift 1 (UPF1) was predicted as the potential target of circular RNA_LARP4 and was upregulated via overexpression of circular RNA_LARP4 in GC. Circular RNA_LARP4 inhibits GC cell proliferation and metastasis via targeting UPF1 in vitro, which might provide a new tumor suppressor in GC development.

Functional remodeling of intraperitoneal macrophages by oncolytic adenovirus restores anti-tumor immunity for peritoneal metastasis of gastric cancer

Intraperitoneal tumor-associated macrophages (TAMs) are involved in evading anti-tumor immunity and promoting the peritoneal metastasis (PM) of gastric cancer (GC). Oncolytic viruses are known to induce the activation of host anti-tumor immunity in addition to tumor lysis. This study investigated whether a wild-type p53-loading telomerase-specific oncolytic adenovirus (OBP-702) could elicit the remodeling of intraperitoneal macrophages and enhance the efficacy of immune therapy. Increased numbers of CD163 TAMs and few CD8+ lymphocytes were immunohistochemically observed in clinical samples with PM, which suggested that TAMs were associated with the suppression of anti-tumor immunity. OBP-702 induced immunogenic cell death and upregulated PD-L1 expression in human and murine GC cell lines. Intraperitoneal administration of OBP-702 increased recruitment of CD8+ lymphocytes into the PM via the functional remodeling of intraperitoneal macrophages from TAM towards a pro-inflammatory phenotype, resulting in significantly suppressed tumor growth for the in vivo model. Furthermore, the combination of intraperitoneal OBP-702 with anti-PD-1 Antibody enhanced anti-tumor immunity and prolonged the survival of mice bearing PM. Intraperitoneal immunotherapy using OBP-702 restores anti-tumor immunity via the remodeling of intraperitoneal macrophages in addition to direct tumor lysis and cooperates with immune checkpoint inhibitors to suppress PM in GC.

MicroRNA-431-5p inhibits angiogenesis, lymphangiogenesis, and lymph node metastasis by affecting TGF-β1/SMAD2/3 signaling via ZEB1 in gastric cancer.

Accumulating evidence suggests that lymphangiogenesis plays a crucial role in lymphatic metastasis, leading to tumor immune tolerance. However, the specific mechanism remains unclear. In this study, miR-431-5p was markedly downregulated in both gastric cancer(GC) tissues and plasma exosomes, and its expression were correlated negatively with LN metastasis and poor prognosis. Mechanistically, miR-431-5p weakens the TGF-β1/SMAD2/3signaling pathway by targeting ZEB1, thereby suppressing the secretion of VEGF-A and ANG2, which in turn hinders angiogenesis, lymphangiogenesis, andlymph node(LN) metastasis in GC. Experiments using a popliteal LN metastasis model in BALB/c nude mice demonstrated that miR-431-5p significantly reduced popliteal LN metastasis. Additionally, miR-431-5p enhances the efficacy of anti-PD1 treatment, particularly when combined with galunisertib, anti-PD1 treatment showing a synergistic effect in inhibiting GC progression in C57BL/6 mice. Collectively, these findings suggest that miR-431-5p may modulate the TGF-β1/SMAD2/3 pathways by targeting ZEB1 to impede GC progression, angiogenesis, and lymphangiogenesis, making it a promising therapeutic target for GC management.

68Ga-FAPI-04 positron emission tomography/CT and laparoscopy for the diagnosis of occult peritoneal metastasis in newly diagnosed locally advanced gastric cancer: study protocol of a single-centre prospective cohort study

IntroductionAccurate baseline clinical staging is critical to inform treatment decision-making for patients with gastric cancers. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer and mainly...

Curcumin inhibits the growth and invasion of gastric cancer by regulating long noncoding RNA AC022424.2.

Gastric cancer, characterized by a multifactorial etiology and high heterogeneity, continues to confound researchers in terms of its pathogenesis. Curcumin, a natural anticancer agent, exhibits therapeutic promise in gastric cancer. Its effects include promoting cell apoptosis, curtailing tumor angiogenesis, and enhancing sensitivity to radiation and chemotherapy. Long noncoding RNAs (lncRNAs) have garnered significant attention as biomarkers for early screening, diagnosis, treatment, and drug response because of their remarkable specificity and sensitivity. Recent investigations have revealed an association between aberrant lncRNA expression and early diagnosis, clinical staging, metastasis, drug sensitivity, and prognosis in gastric cancer. A profound understanding of the intricate mechanisms through which lncRNAs influence gastric cancer development can provide novel insights for precision treatment and tailored management of patients with gastric cancer. This study aimed to unravel the potential of curcumin in suppressing the malignant behavior of gastric cancer cells by upregulating specific lncRNAs and modulating gastric cancer onset and progression. To identify lncRNAs associated with curcumin treatment and investigate the role of lncRNA AC022424.2 in the effects of curcumin on gastric cancer cell apoptosis, proliferation, and invasion. Furthermore, these findings were validated in clinical samples. The study employed CCK-8 assays to assess the impact of curcumin on gastric cancer cell proliferation, flow cytometry to investigate its effects on apoptosis, and scratch and Transwell assays to evaluate its influence on the migration and invasion of BGC-823 and MGC-803 cells. Western blotting was used to gauge changes in the protein expression levels of CDK6, CDK4, Bax, Bcl-2, caspase-3, P65, and the PI3K/Akt/mTOR pathway in gastric cancer cell lines after curcumin treatment. Differential expression of lncRNAs before and after curcumin treatment was assessed using lncRNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in BGC-823 and MGC-803 cells. AC022424.2-1 knockdown BGC-823 and MGC-803 cells were generated to scrutinize the impact of lncRNA AC022424.2 on apoptosis, proliferation, migration, and invasion of gastric cancer cells. Western blotting was performed to ascertain changes in the expression of proteins implicated in the PI3K/Akt/mTOR and NF-κB signaling pathways. RT-PCR was employed to measure lncRNA AC022424.2 expression in clinical gastric cancer tissues and to correlate its expression with clinical pathological characteristics. Curcumin induced apoptosis and hindered proliferation, migration, and invasion of gastric cancer cells in a dose- and time-dependent manner. LncRNA AC022424.2 was upregulated after curcumin treatment, and its knockdown enhanced cancer cell aggressiveness. LncRNA AC022424.2 may have affected cancer cells via the PI3K/Akt/mTOR and NF-κB signaling pathways. LncRNA AC022424.2 downregulation was correlated with lymph node metastasis, making it a potential diagnostic and prognostic marker. Curcumin has potential anticancer effects on gastric cancer cells by regulating lncRNA AC022424.2. This lncRNA plays a significant role in cancer cell behavior and may have clinical implications in diagnosis and prognosis evaluation. The results of this study enhance our understanding of gastric cancer development and precision treatment.

Machine learning for identifying tumor stemness genes and developing prognostic model in gastric cancer.

Gastric cancer presents a formidable challenge, marked by its debilitating nature and often dire prognosis. Emerging evidence underscores the pivotal role of tumor stem cells in exacerbating treatment resistance and fueling disease recurrence in gastric cancer. Thus, the identification of genes contributing to tumor stemness assumes paramount importance. Employing a comprehensive approach encompassing ssGSEA, WGCNA, and various machine learning algorithms, this study endeavors to delineate tumor stemness key genes (TSKGs). Subsequently, these genes were harnessed to construct a prognostic model, termed the Tumor Stemness Risk Genes Prognostic Model (TSRGPM). Through PCA, Cox regression analysis and ROC curve analysis, the efficacy of Tumor Stemness Risk Scores (TSRS) in stratifying patient risk profiles was underscored, affirming its ability as an independent prognostic indicator. Notably, the TSRS exhibited a significant correlation with lymph node metastasis in gastric cancer. Furthermore, leveraging algorithms such as CIBERSORT to dissect immune infiltration patterns revealed a notable association between TSRS and monocytes and other cell. Subsequent scrutiny of tumor stemness risk genes (TSRGs) culminated in the identification of CDC25A for detailed investigation. Bioinformatics analyses unveil CDC25A's implication in driving the malignant phenotype of tumors, with a discernible impact on cell proliferation and DNA replication in gastric cancer. Noteworthy validation through in vitro experiments corroborated the bioinformatics findings, elucidating the pivotal role of CDC25A expression in modulating tumor stemness in gastric cancer. In summation, the established and validated TSRGPM holds promise in prognostication and delineation of potential therapeutic targets, thus heralding a pivotal stride towards personalized management of this malignancy.

MEF2D facilitates liver metastasis of gastric cancer cells through directly inducing H1X under IL-13 stimulation

Liver metastasis is the most common metastatic occurrence in gastric cancer patients, although the precise mechanism behind it remains unclear. Through a combination of proteomics and quantitative RT-PCR, our study has revealed a significant correlation between the upregulation of myocyte enhancer factor-2D (MEF2D) and both distant metastasis and poor prognosis in gastric cancer patients. In mouse models, we observed that overexpressing or knocking down MEF2D in gastric cancer cells respectively promoted or inhibited liver metastasis. Furthermore, our research has demonstrated that MEF2D regulates the transcriptional activation of H1X by binding to the H1X promoter. This regulation leads to the upregulation of H1X, which, in turn, promotes the in vivo metastasis of gastric cancer cells along with the upregulation of the downstream gene β-CATENIN. Additionally, we found that the expression of MEF2D and H1X at both mRNA and protein levels can be induced by the inflammatory factor IL-13, and this induction exhibits a time gradient dependence. In human gastric cancer tissues, the expression of IL13RA1, the receptor for IL-13, positively correlates with the expression of MEF2D and H1X. IL13RA1 has been identified as an intermediate receptor through which IL-13 regulates MEF2D. In conclusion, our findings suggest that MEF2D plays a crucial role in promoting liver metastasis of gastric cancer by upregulating H1X and downstream target β-CATENIN in response to IL-13 stimulation. Targeting MEF2D could therefore be a promising therapeutic strategy for the clinical management of gastric cancer. Statement of significanceMEF2D promotes its transcriptional activation in gastric cancer cells by binding to the H1X promoter and is upregulated by IL-13-IL13RA1, thereby promoting distant metastasis of gastric cancer.

YTHDC1 promotes the malignant progression of gastric cancer by promoting ROD1 translocation to the nucleus

RNA-binding proteins (RBPs) make vital impacts on tumor progression and are important potential targets for tumor treatment. Previous studies have shown that RBP regulator of differentiation 1 (ROD1), enriched in the nucleus, is abnormally expressed and functions as a splicing factor in tumors; however, the mechanism underlying its involvement in gastric cancer (GC) is unknown. In this study, ROD1 is found to stimulate GC cell proliferation and metastasis and is related to poor patient prognosis. In vitro experiments showed that ROD1 influences GC proliferation and metastasis through modulating the imbalance of the level of the oncogenic gene OIP5 and the tumor suppressor gene GPD1L. Further studies showed that the N6-methyladenosine (m6A) “reader” protein YTHDC1 can interact with ROD1 and regulate the balance of the expression of the downstream molecules OIP5/GPD1L by promoting the nuclear enrichment of ROD1. Therefore, YTHDC1 stimulates GC development and progression through modulating nuclear enrichment of the splicing factor ROD1.Graphical

Vagus nerve signal has an inhibitory influence on the development of peritoneal metastasis in murine gastric cancer

The vagus nerve is the only pathway for transmitting parasympathetic signals between the brain and thoracoabdominal organs, thereby exhibiting anti-inflammatory functions through the cholinergic anti-inflammatory pathway. Despite often being resected during lymph node dissection in upper gastrointestinal cancer surgery, the impact of vagotomy on postoperative outcomes in gastric cancer patients remains unclear. Sub-diaphragmatic vagotomy was performed on C57BL/6 mice. Three weeks later, syngeneic murine gastric cancer cell line YTN16P was injected into the peritoneal cavity, and the number of peritoneal metastases (PM) on the mesentery and omentum compared with control mice. The phenotypes of immune cells in peritoneal lavage and omental milky spots one day after tumor inoculation were analyzed using flow cytometry and immunohistochemistry. Intraperitoneal transfer of 3 × 105 YTN16P significantly increased the number of metastatic nodules on the mesentery in the vagotomy group compared to the control group. The omental metastasis grade was also significantly higher in the vagotomy group. Phenotypic analysis of immune cells in peritoneal lavage did not reveal significant differences after vagotomy. However, vagotomized mice exhibited a notable increase in milky spot area, with a higher presence of cytokeratin(+) tumor cells, F4/80(+) macrophages, and CD3(+) T cells. Vagus nerve signaling appears to regulate the immune response dynamics within milky spots against disseminated tumor cells and inhibits the development of PM. Preserving the vagus nerve may offer advantages in advanced gastric cancer surgery to reduce peritoneal recurrence.

A bibliometric analysis of gastric cancer liver metastases: advances in mechanisms of occurrence and treatment options.

Gastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide, and its poor prognosis is predominantly attributed to distant metastasis. The liver is the primary site of GC metastasis. However, there is no universally approved treatment regimen for liver metastasis in GC. The aim of this article is to review the current research status and trends of liver metastasis of GC worldwide. The authors utilized the Web of Science Core Collection database to identify articles on liver metastasis from GC published between 2000 and 2022. The authors used bibliometric methods to analyze authors, institutions, countries, journals, and references through CiteSpace and VOSviewer. A total of 1003 articles were included in this study. Japan published the most articles in the field, followed by China. Nagoya University is the leading institution in the field of liver metastases in GC. Yasuhiro Kodera from Japan has made significant achievements in this area. The authors identified GC to be the most influential journal in this field. Using cluster analysis, the keywords were divided into four major clusters:(1) the molecular mechanism of GC liver metastasis, (2) prognosis, (3) liver resection, and (4) chemotherapy. Our study systematically summarizes the results of GC liver metastasis research from 2000 to 2022 and describes and predicts research hotspots and trends on a global scale. Research on the molecular mechanisms of GC liver metastasis will become a hot topic in the future, and the expansion of the surgical treatment scope and the advancement of translational therapy will benefit more patients.

A clinicopathologic feature-based nomogram for preoperative estimation of splenic hilar lymph node metastasis in advanced proximal gastric cancer without invasion of the greater curvature

BackgroundThe indications for splenic hilar lymph node dissection in advanced proximal gastric cancer without invasion of the greater curvature are controversial. We aimed to develop a preoperative nomogram for individualized prediction of splenic hilar lymph node metastasis in non–greater curvature advanced proximal gastric cancer. MethodsFrom January 2014 to December 2021, 558 patients with non–greater curvature advanced proximal gastric cancer who underwent D2 lymphadenectomy (including splenic hilar lymph node) were retrospectively analyzed and divided into a training cohort (n = 361) and validation cohort (n = 197), depending on the admission time. A preoperative predictive nomogram of splenic hilar lymph node metastasis was established based on independent predictors identified by multivariate analysis, and the performance and prognostic value were confirmed. ResultsIn the training and validation cohorts, 48 (13.3%) and 24 patients (12.2%) had pathologically confirmed splenic hilar lymph node metastasis, respectively. Tumor located in the posterior wall, tumor size ≥5 cm, Borrmann type IV, and splenic hilar lymph node lymphadenectasis on computed tomography were preoperative factors independently associated with splenic hilar lymph node metastasis. The nomogram developed based on these four parameters had a high concordance index of 0.850 (95% confidence interval, 0.793–0.907) and 0.825 (95% confidence interval, 0.743–0.908) in the training and validation cohorts, respectively, with well-fitting calibration plots and better net benefits in the decision curve analysis. In addition, disease-free survival and overall survival were significantly shorter in the high-risk group, with hazard ratios of 3.660 (95% confidence interval, 2.228–6.011; log-rank P < .0001) and 3.769 (95% confidence interval, 2.279–6.231; log-rank P < .0001), respectively. ConclusionThe nomogram has good performance in predicting the risk of splenic hilar lymph node metastasis in non–greater curvature advanced proximal gastric cancer preoperatively, which can help surgeons make rational clinical decisions.

Establishment and validation of a risk score model based on EUS: assessment of lymph node metastasis in early gastric cancer

Lymph node metastasis significantly affects the prognosis of early gastric cancer patients. Endoscopic ultrasonography (EUS) plays a crucial role in the preoperative assessment of early gastric cancer. This study evaluated the efficacy of EUS in identifying lymph node metastasis in early gastric cancer patients and developed a risk score model to aid in choosing the best treatment options. We retrospectively analyzed the effectiveness of EUS for detecting lymph node metastasis in early gastric cancer patients. A risk score model for predicting lymph node metastasis preoperatively was created using independent risk factors identified through binary logistic regression analysis and subsequently validated. Receiver operating characteristic (ROC) curves were generated for both the development and validation cohorts. The overall accuracy of EUS in identifying lymph node metastasis was 85.3%, although its sensitivity (29.2%) and positive predictive value (38.7%) were relatively low. Patients were categorized based on preoperative risk factors for lymph node metastasis, including tumor size ≥20 mm, lymph nodes ≥10 mm, BMI ≥24 kg/m2, and lymph node metastasis on CT scans. A 7-point risk score model was developed to assess the likelihood of lymph node metastasis. The areas under the ROC curve (AUCs) for the development and validation sets were 0.842 and 0.837, respectively, with sensitivities of 64% and 79%, respectively. We developed a practical risk score model based on preoperative factors to help EUS predict lymph node metastasis in early gastric cancer patients, guiding the selection of optimal treatment approaches for these patients.