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1.
J Glob Health ; 14: 04025, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38180951

RESUMEN

Background: Stomach and esophageal cancer exhibit high morbidity and mortality rate in China, resulting in substantial disease burdens. It is imperative to identify the temporal trends of stomach and esophageal cancer from 1990 to 2019 and project future trends until 2030, which can provide valuable information for planning effective management and prevention strategies. Methods: We collected and analysed data from the Global Burden of Disease (GBD) between 1990 and 2019, including incidence, mortality, disability-adjusted life years (DALYs), age-standardised incidence rate (ASIR), mortality rate (ASMR) and DALYs rate. We also calculated and reported the proportion of mortality and DALYs attributable to risk factors by sex in China and different regions. The Bayesian age-period-cohort model was applied to project future trends until 2030. Results: The new cases, deaths and DALYs of stomach and esophageal cancer increased from 1990 to 2019. However, the ASIR, ASMR and age-standardised DALYs rates for stomach and esophageal cancer all decreased during the same period. These changes may be related to risks, such as smoking and diet. Furthermore, we utilised the projection model to estimate that the ASIR and ASMR of stomach and esophageal cancer among females will likely follow steady downward trends, while the ASMR of stomach cancer among males is expected to exhibit a significant decline. However, the ASIR of stomach and esophageal cancer and the ASMR of esophageal cancer among males are projected to display slight upward trends until 2030. Conclusions: The analysis of stomach and esophageal cancer trends in China from 1990 to 2030 reveals a general decline. However, it is crucial to acknowledge the persistent high burden of both cancers in the country. Adopting healthy lifestyle practices, including the reduction of tobacco and alcohol intake, avoidance of moldy foods and increased consumption of fresh fruits and vegetables can contribute to mitigating the risk of stomach and esophageal cancer. Significantly, the formulation and implementation of well-founded and efficacious public health policies are imperative for alleviating the disease burden in China.


Asunto(s)
Neoplasias Esofágicas , Neoplasias Gástricas , Femenino , Masculino , Humanos , Carga Global de Enfermedades , Neoplasias Esofágicas/epidemiología , Neoplasias Gástricas/epidemiología , Teorema de Bayes , China/epidemiología
2.
World J Surg Oncol ; 22(1): 21, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38243254

RESUMEN

BACKGROUND: After radical surgery, early detection of recurrence and metastasis is a crucial factor in enhancing the prognosis and survival of patients with gastric cancer (GC). Therefore, assessing the risk of recurrence in gastric cancer patients and determining the timing for postoperative recurrence is crucial. METHODS: The clinicopathological data of 521 patients with recurrent gastric cancer, who underwent radical gastrectomy at Zhejiang Cancer Hospital between January 2010 and January 2017, were retrospectively analyzed. These patients were randomly divided into two groups: a training group (n = 365) and a validation group (n = 156). In the training set, patients were further categorized into early recurrence (n = 263) and late recurrence (n = 102) groups based on a 2-year boundary. Comparative analyses of clinicopathological features and prognoses were conducted between these two groups. Subsequently, a nomogram for predicting early recurrence was developed and validated. RESULTS: In this study, the developed nomogram incorporated age, serous infiltration, lymph node metastasis, recurrence mode, and the tumour marker CA19-9. In the training cohort, the area under the curve (AUC value) was 0.739 (95% CI, 0.682-0.798), with a corresponding C-index of 0.739. This nomogram was subsequently validated in an independent validation cohort, yielding an AUC of 0.743 (95% CI, 0.652-0.833) and a C-index of 0.743. Furthermore, independent risk factors for prognosis were identified, including age, absence of postoperative chemotherapy, early recurrence, lymph node metastasis, abdominal metastasis, and vascular cancer embolus. CONCLUSION: Independent risk factors for gastric cancer recurrence following radical surgery were utilized to construct a nomogram for predicting early relapse. This nomogram effectively assesses the risk of recurrence, aids in treatment decision-making and follow-up planning in clinical settings, and demonstrated strong performance in the validation cohort.


Asunto(s)
Nomogramas , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirugía , Metástasis Linfática , Gastrectomía/efectos adversos
3.
Front Immunol ; 14: 1282176, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38143746

RESUMEN

As one of the deadliest cancers of the gastrointestinal tract, there has been limited improvement in long-term survival rates for gastric cancer (GC) in recent decades. The poor prognosis is attributed to difficulties in early detection, minimal opportunity for radical resection and resistance to chemotherapy and radiation. Macrophages are among the most abundant infiltrating immune cells in the GC stroma. These cells engage in crosstalk with cancer cells, adipocytes and other stromal cells to regulate metabolic, inflammatory and immune status, generating an immunosuppressive tumour microenvironment (TME) and ultimately promoting tumour initiation and progression. In this review, we summarise recent advances in our understanding of the origin of macrophages and their types and polarisation in cancer and provide an overview of the role of macrophages in GC carcinogenesis and development and their interaction with the GC immune microenvironment and flora. In addition, we explore the role of macrophages in preclinical and clinical trials on drug resistance and in treatment of GC to assess their potential therapeutic value in this disease.


Asunto(s)
Neoplasias Gástricas , Humanos , Macrófagos , Células del Estroma/patología , Microambiente Tumoral
4.
Materials (Basel) ; 16(24)2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38138658

RESUMEN

In the long-term working state, stains such as dust, oil, and charged particles in the environment are prone to deposit on the surface of the power equipment, which has great security risks. To achieve anti-stain performance, fluorocarbon composite coating with a low surface energy was prepared and studied. In this paper, SiO2 nanoparticles were used as inorganic fillers and fluorocarbon resin was used as the substrate to form anti-stain coatings. By adjusting and optimizing the ratio of fillers and organic resins, coatings with different static contact angles were constructed. The optimum composite coating has a contact angle of 151 ± 2° and a surface energy of 9.6 mJ/m2. After high-temperature treatment (up to 200 °C), immersion in corrosive solutions (pH 3-11), and sandpaper abrasion (after 5 abrasion cycles), the coating has been proven to show good thermal, chemical and mechanical stability. Our study provides significant research and market opportunities for the anti-stain application of the fluorocarbon composite coating on power equipment.

5.
Materials (Basel) ; 16(22)2023 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-38005152

RESUMEN

In a high-moisture environment where dust and coastal saltwater are prevalent, the stability of power equipment can be adversely affected. This issue can result in equipment downtime, particularly for transformers, severely disrupting the continuous operation of DC transmission systems. To address this challenge, a superhydrophobic modified fluorosilicone coating was developed, incorporating anti-stain properties. To tackle this issue comprehensively, an orthogonal experiment was conducted, involving six factors and three levels. The study focused particularly on assessing the impact of water-repellent recovery agents, nanofillers, antistatic agents, anti-mold agents, leveling agents, as well as wetting and dispersing agents on the coating's surface tension. The results demonstrate that selecting an appropriate base resin and incorporating well-matched functional additives played a central role in effectively reducing the surface tension of the coating. Consequently, optimized coatings exhibited exceptional resistance to stains and displayed strong corrosion resistance.

6.
Theranostics ; 13(14): 5130-5150, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37771777

RESUMEN

Background: Current clinical treatments for gastric cancer (GC), particularly advanced GC, lack infallible therapeutic targets. The 3'-untranslated region (3'-UTR) has attracted increasing attention as a drug target. Methods: In vitro and in vivo experiments were conducted to determine the function of FN1 3'-UTR and FN1 protein in invasion and metastasis. RNA pull-down assay and high-throughput sequencing were used to screen the factors regulated by FN1 3'-UTR and construct the regulatory network. Western blotting and polymerase chain reaction were used to examine the correlation of intermolecular expression levels. RNA-binding protein immunoprecipitation was used to verify the correlation between FN1 3'-UTR and target mRNAs. Results: The FN1 3'-UTR may have stronger prognostic implications than the FN1 protein in GC patients. Upregulation of FN1 3'-UTR significantly promoted the invasive and metastatic abilities of GC cells to a greater extent than FN1 protein in vitro and in vivo. A novel regulatory network was constructed based on the FN1 3'-UTR-let-7i-5p-THBS1 axis, wherein FN1 3'-UTR displayed stronger oncogenic effects than the FN1 protein. Conclusions: FN1 3'-UTR may be a better therapeutic target for constructing targeted drugs in GC than the FN1 protein.


Asunto(s)
Fibronectinas , MicroARNs , Neoplasias Gástricas , Humanos , Regiones no Traducidas 3'/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Fibronectinas/genética , Fibronectinas/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , Neoplasias Gástricas/patología
7.
ACS Nano ; 17(15): 14461-14474, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37367941

RESUMEN

Intravenous administration of oncolytic adenoviruses (OVs) is a hopeful tumor therapeutic modality. However, the sharp clearance of OVs by the immune system dampens its effectiveness. Many studies have attempted to extend the circulation of intravenously administered OVs, almost all by preventing OVs from binding to neutralizing antibodies and complements in the blood, but the results have not been satisfactory. In contrast to previous conclusions, we found that the key to improving the circulation of OVs is to prevent the formation of the virus-protein corona rather than simply preventing the binding of neutralizing antibodies or complements to OVs. After identifying the key protein components of the virus-protein corona, we proposed a virus-protein corona replacement strategy, where an artificial virus-protein corona was formed on OVs to completely prevent the interaction of OVs with key virus-protein corona components in the plasma. It was found that this strategy dramatically prolonged the circulation time of OVs by over 30 fold and increased the distribution of OVs in tumors by over 10-fold, resulting in superior antitumor efficacy in primary and metastatic tumor models. Our finding provides a perspective on intravenous delivery of OVs, shifting the focus of future studies from preventing OV binding with neutralization antibodies and complements to preventing OVs from interacting with key virus-protein corona components in the plasma.


Asunto(s)
Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Corona de Proteínas , Humanos , Virus Oncolíticos/genética , Viroterapia Oncolítica/métodos , Adenoviridae/genética , Neoplasias/terapia , Anticuerpos Neutralizantes
8.
Nat Commun ; 14(1): 2933, 2023 05 22.
Artículo en Inglés | MEDLINE | ID: mdl-37217527

RESUMEN

Oncolytic adenovirus (Ad) infection promotes intracellular autophagy in tumors. This could kill cancer cells and contribute to Ads-mediated anticancer immunity. However, the low intratumoral content of intravenously delivered Ads could be insufficient to efficiently activate tumor over-autophagy. Herein, we report bacterial outer membrane vesicles (OMVs)-encapsulating Ads as microbial nanocomposites that are engineered for autophagy-cascade-augmented immunotherapy. Biomineral shells cover the surface antigens of OMVs to slow their clearance during in vivo circulation, enhancing intratumoral accumulation. After entering tumor cells, there is excessive H2O2 accumulation through the catalytic effect of overexpressed pyranose oxidase (P2O) from microbial nanocomposite. This increases oxidative stress levels and triggers tumor autophagy. The autophagy-induced autophagosomes further promote Ads replication in infected tumor cells, leading to Ads-overactivated autophagy. Moreover, OMVs are powerful immunostimulants for remolding the immunosuppressive tumor microenvironment, facilitating antitumor immune response in preclinical cancer models in female mice. Therefore, the present autophagy-cascade-boosted immunotherapeutic method can expand OVs-based immunotherapy.


Asunto(s)
Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Femenino , Animales , Ratones , Adenoviridae/genética , Membrana Externa Bacteriana , Peróxido de Hidrógeno , Neoplasias/patología , Autofagia/fisiología , Virus Oncolíticos/genética , Microambiente Tumoral
9.
J Oncol ; 2023: 8629166, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36747903

RESUMEN

Background: While early gastric cancer (EGC) patients are likely to experience relatively long postoperative survival, certain disease-related findings are associated with a poorer prognosis. This study sought to develop and validate a novel predictive model capable of estimating conditional disease-specific survival (CDSS) in EGC patients. Methods: A total of 3016 patients diagnosed with pT1NxM0 GC after gastrectomy between 1998 and 2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) database and were separated into training and validation cohorts. Kaplan‒Meier curves and log-rank tests were employed to evaluate DSS, after which univariate and multivariate Cox regression analyses were used to construct a predictive nomogram and to estimate CDSS at 1, 2, and 3 years postoperatively in these patients. Results: In the training cohort, the 3-year CDSS rose from 89.1% to 94.6% from 0 to 5 years postoperatively, while the 5-year CDSS rose from 84.5% to 92.0%. Cox regression analyses led to the construction of a nomogram that was able to reliably predict 3- and 5-year CDSS at 1, 2, and 3 years postoperatively (all P < 0.05) based upon patient age, tumor size, pT stage, pN stage, and the number of retrieved lymph nodes. This model exhibited good discriminative power in the training and validation cohorts (concordance index: 0.791 and 0.813, respectively), and nomogram calibration curves confirmed that actual and predicted survival outcomes were close to one another. Conclusions: We herein developed a nomogram capable of accurately predicting the CDSS of EGC patients that had survived for multiple years after undergoing surgery.

10.
Cancer Med ; 12(1): 879-897, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35635121

RESUMEN

BACKGROUND: Most human genes have diverse transcript isoforms, which mainly arise from alternative cleavage and polyadenylation (APA) at 3' ends. N7-methylguanosine (m7 G) is also an essential epigenetic modification at the 5' end. However, the contribution of these two RNA modifications to the development, prognosis, regulation mechanisms, and drug sensitivity of gastric cancer (GC) is unclear. METHODS: The expression data of 2412 patients were extracted from 12 cohorts and the RNA modification patterns of 20 marker genes were systematically identified into phenotypic clusters using the unsupervised clustering approach. Following that, we developed an RNA modification model (RMscore) to quantify each GC patient's RNA modification index. Finally, we examined the correlation between RMscore and clinical features such as survival outcomes, molecular subtypes identified by the Asian Cancer Research Group (ACRG), posttranscriptional regulation, and chemotherapeutic sensitivity in GC. RESULTS: The samples were categorized into two groups on the basis of their RMscore: high and low. The group with a low RMscore had a bad prognosis. Moreover, the low RMscore was associated with KRAS, Hedgehog, EMT, and TGF-ß signaling, whereas a high RMscore was related to abnormal cell cycle signaling pathway activation. The findings also revealed that the RMscore contributes to the regulation of the miRNA-mRNA network. Drug sensitivity analysis revealed that RMscore is associated with the response to some anticancer drugs. CONCLUSIONS: The RMscore model has the potential to be a useful tool for prognosis prediction in patients with GC. A comprehensive investigation of APA-RNA and m7 G-RNA modifications may reveal novel insights into the epigenetics of GC and aid in the development of more effective treatment strategies.


Asunto(s)
MicroARNs , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Regulación Neoplásica de la Expresión Génica , Pronóstico , ARN Mensajero/metabolismo
11.
Materials (Basel) ; 15(19)2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36234366

RESUMEN

The organic piezoelectric polymer polyvinylidene fluoride (PVDF) has attracted extensive research because of its excellent flexibility and mechanical energy-harvesting properties. Here, the electrospinning technique was taken to fabricate synthesized fiber membranes of a PVDF/cellulose acetate (CA) composite. The obtained PVDF/CA electrospun fiber membranes (EFMs) were employed to prepare a flexible nanogenerator. XRD and FTIR spectroscopy revealed the enhancement of piezoelectric behavior due to an increase in ß-phase in PVDF/CA EFMs compared with cast films. The PVDF/CA fibers (mass ratio of PVDF to CA = 9:1) showed an output voltage of 7.5 V and a short-circuit current of 2.1 µA under mechanical stress of 2 N and frequency of 1 Hz, which were 2.5 and two times greater than those of the pure PVDF fibers, respectively. By charging a 4.7 µF capacitor for 15 min with the voltage generated by the PVDF/CA EFMs, nine LED lamps could be lit. The work provides an effective approach to enhancing the piezoelectric effects of PVDF for low-power electronic loading of macromolecule polymers.

12.
Nano Lett ; 22(12): 5055-5064, 2022 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-35583490

RESUMEN

Oncolytic viruses (OVs) have been widely used as anticancer therapeutics because of their systemic immune responses during viral replication. However, the low enrichment of OVs within tumors and limited immune activation have hindered their clinical application. Herein, we proposed the concept of bacteria-assisted targeting of OVs to tumors, with liposome-cloaked oncolytic adenoviruses (OAs) conjugated onto tumor-homing Escherichia coli BL21 (designated as E. coli-lipo-OAs) for enhanced cancer immunotherapy. Notably, the enrichment of OAs transported by self-propelled bacterial microbe vehicles in E. coli-lipo-OAs in a nonsmall cell lung tumor can be potentiated by more than 170-fold compared with that of intravenously injected bare OAs. In vivo studies further revealed that E. coli-lipo-OAs administered intravenously significantly enhanced antitumor immunity through bacterial-viral-augmented immune responses. Our findings suggest that the self-driving microbe vehicle as a systemic delivery system for OVs can be a potent platform for developing future anticancer biotherapeutics at the clinical level.


Asunto(s)
Neoplasias , Viroterapia Oncolítica , Virus Oncolíticos , Escherichia coli , Humanos , Inmunoterapia , Neoplasias/terapia , Virus Oncolíticos/genética
13.
BMC Cancer ; 22(1): 474, 2022 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-35488236

RESUMEN

BACKGROUND: The Lauren classification of gastric tumors strongly correlates with prognosis. The purpose of this study was to explore the specific molecular mechanism of Lauren classification of gastric cancer and provide a possible theoretical basis for the treatment of gastric cancer. METHODS: We standardized the gene expression data of five Gene Expression Omnibus gastric cancer databases and constructed a Weighted Co-expression Network Analysis (WGCNA) model based on clinicopathological information. The overall survival (OS) and disease-free survival (DFS) curves were extracted from the Cancer Genome Atlas (TCGA) and GSE62254 databases. Western blotting was used to measure protein expression in cells and tissues. Scratch and transwell experiments were used to test the migration ability of tumor cells. Immunohistochemistry was used to measure tissue protein expression in clinical tissue samples to correlate to survival data. RESULTS: The WGCNA model demonstrated that blue cyan was highly correlated with the Lauren classification of the tumor (r = 0.24, P = 7 × 1016). A protein-protein interaction network was used to visualize the genes in the blue cyan module. The OS and PFS TCGA analysis revealed that LMOD1 was a gene of interest. The proportion of diffuse gastric cancer patients with high expression of LMOD1 was significantly higher than that of intestinal type patients. LMOD1 promoted the migration of gastric cancer cells by regulating the FAK-Akt/mTOR pathway in vitro. Additionally, a Gene Set Enrichment Analysis using the TCGA and GSE62254 databases, and western blot data, showed that LMOD1 could promote an epithelial-mesenchymal transition (EMT), thus potentially affecting the occurrence of peritoneal metastasis of gastric cancer. Immunohistochemistry showed that LMOD1 was highly expressed in cancer tissues, and the prognosis of patients with high LMOD1 expression was poor. CONCLUSION: LMOD1 is an oncogene associated with diffuse gastric cancer and can affect the occurrence and development of EMT by regulating the FAK-Akt/mTOR pathway. LMOD1 can therefore promote peritoneal metastasis of gastric cancer cells and can be used as a novel therapeutic target for gastric cancer.


Asunto(s)
Neoplasias Peritoneales , Neoplasias Gástricas , Autoantígenos , Línea Celular Tumoral , Movimiento Celular/genética , Proteínas del Citoesqueleto/genética , Humanos , Oncogenes , Neoplasias Peritoneales/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Gástricas/patología , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo
14.
Front Pharmacol ; 13: 777612, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35295342

RESUMEN

Background: Spindle and kinetochore-related complex subunit 3 (SKA3), a member of the SKA family of proteins, is associated with the progression of multiple cancers. However, the role of SKA3 in gastric cancer has not been studied. Methods: The expression levels of SKA3 and dual-specificity phosphatase 2 (DUSP2) proteins were detected by immunohistochemistry. The effects of SKA3 and DUSP2 on the proliferation, migration, invasion, adhesion, and epithelial-mesenchymal transition of gastric cancer were studied in vitro and in vivo. Results: Immunohistochemical analysis of 164 cases of gastric cancer revealed that high expression of SKA3 was negatively correlated with DUSP2 expression and related to N stage, peritoneal metastasis, and poor prognosis. In vitro studies showed that silencing SKA3 expression inhibited the proliferation, migration, invasion, adhesion and epithelial-mesenchymal transition of gastric cancer. In vivo experiments showed that silencing SKA3 inhibited tumor growth and peritoneal metastasis. Mechanistically, SKA3 negative regulates the tumor suppressor DUSP2 and activates the MAPK/ERK pathway to promote gastric cancer. Conclusion: Our results indicate that the SKA3-DUSP2-ERK1/2 axis is involved in the regulation of gastric cancer progression, and SKA3 is a potential therapeutic target for gastric cancer.

15.
Hum Cell ; 35(2): 599-612, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34981466

RESUMEN

RNA-binding protein with multiple splicing 2 (RBPMS2) is a critical gene that encodes a member of the RNA-recognition-motif-containing protein family and is involved in the development and dedifferentiation of digestive smooth muscle cells. However, whether RBPMS2 has an effect on the prognosis of gastric cancer (GC) and its possible mechanism during GC progression remain unknown. Here, we collected 596 GC patients who underwent curative surgical resection to evaluate expression of RBPMS2. RBPMS2 was upregulated in GC tissues, and was associated with lymph node metastasis. We analysis the KEGG pathway and GO biological processes, cellular component and molecular function of RBPMS2 interactive genes, as well as RBPMS2-binding partner ESRP1 interactive genes. We also focus on the correlation analysis between EMT-related genes and RBPMS2/ESRP1. Finally, we analysed the correlation between RBPMS2 expression and chemotherapeutic drugs which may assist in GC therapy and demonstrated that RBPMS2 expression was associated with tumour mutation burden (TMB) and Microsatellite Instability (MSI), as well as immune infiltration level in GC.


Asunto(s)
Neoplasias Gástricas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Humanos , Metástasis Linfática , Inestabilidad de Microsatélites , Miocitos del Músculo Liso/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología
16.
Int Immunopharmacol ; 101(Pt B): 108258, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34678693

RESUMEN

BACKGROUNDS: Advanced gastric cancer (GC) remains difficult to conduct individualized prognostic evaluations owing to the highly heterogeneous nature and the low level of immune cell infiltration (ICI) within GC tumors. This study thus sought to develop a model capable of classifying GC patients according to the degree of tumor ICI and gauging prognosis. METHODS: The degree of ICI in GC patients from the GSE15459, GSE57303, and GSE62254 datasets were estimated, and these values were used to group patients via an unsupervised clustering approach, after which ICI cluster-related genes were identified the association with prognosis through Cox and LASSO regression analyses. The primary risk genes were then verified by immunohistochemical staining of GC tumor tissue samples. RESULTS: 570 patients were clustered into three clusters and 289 ICI cluster-related genes were identified. A prognostic model based on the expression of six crucial ICI risk genes (CXCL11, RBPMS2, LOC400043, JCHAIN, CT83, and ORM1) wa constructed. Patients identified as being high risk based upon the model have poorer clinical features and survival outcomes compared to the other patients. Adjuvant intervention was found to be more beneficial for patients expressing high levels of RBPMS2, JCHAIN, or ORM1. Furthermore, patients expressing low levels of JCHAIN or CT83 in GC tumor tissues were verified to exhibit a significantly better prognosis in a CMU cohort. CONCLUSION: Advanced GC patients were successfully grouped into clusters based on the degree of intratumoral ICI, and a prognostic evaluation model based on 6 ICI risk genes was developed and validated.


Asunto(s)
Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias Gástricas/diagnóstico , Antígenos de Neoplasias/genética , Biomarcadores de Tumor/metabolismo , Quimiocina CXCL11/genética , Conjuntos de Datos como Asunto , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Estadificación de Neoplasias , Pronóstico , Análisis de Regresión , Riesgo , Índice de Severidad de la Enfermedad , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Análisis de Supervivencia
17.
BMC Gastroenterol ; 21(1): 352, 2021 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-34563111

RESUMEN

BACKGROUND: Individuals with pN3 gastric cancer (GC) account for a large proportion of pN + GC, and exhibit poor survival outcomes. The pN3 stage is defined based upon the number of metastatic lymph nodes (mLNs), but the subclassification of pN3 patients based upon the number of examined LNs (eLNs) is rarely performed. METHODS: In total, 2894 pTxN3M0 GC patients in the Surveillance, Epidemiology, and End Results database that had undergone surgery from 2000 to 2016 were selected for analysis. The X-tile software was used to select the optimal cutoff values. Cox proportional regression analyses were used to evaluated hazard ratios corresponding to the risk of death. Selection bias was minimized via propensity score matching (PSM). RESULTS: As the number of eLNs rose, the risk of death for patients trended downwards. Survival analyses indicated that patients with ≤ 31 eLNs exhibited significantly poorer survival outcomes as compared to patients with > 31 eLNs (5-year OS: 18.4% vs. 24.7%), and this result remained significant when analyzing 857 pairs of patients following PSM analysis. Significant differences in prognosis were additionally observed when comparing pN3a and pN3b patients with ≤ 31 or > 31 eLNs under pT3/4a stage. For pT4b stage, pN3a patients with > 31 eLNs also exhibited a better prognosis than other patients. The novel TNM staging system designed exhibited excellent utility as a tool for the prognostic evaluation of this GC patient population. CONCLUSIONS: These results suggest that in pN3 GC, a minimum of 32 LNs should be examined. The novel TNM staging system for pN3 patients described herein, which was developed based upon the number of eLNs, may thus be of value in clinical settings.


Asunto(s)
Neoplasias Gástricas , Humanos , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Estadificación de Neoplasias , Pronóstico , Puntaje de Propensión , Estudios Retrospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía
18.
J Cancer ; 12(18): 5583-5592, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34405019

RESUMEN

Background: Patients with early gastric cancer (EGC) must suffer reoperation if diagnosed with a high possibility of lymph node (LN) metastasis. The purpose of the current study was to develop and validate a model to predict the risk of LN metastasis in elderly patients before endoscopic resection. Methods: A total of 1911 EGC patients who had undergone radical surgery were selected and assigned randomly (2:1) to either the training cohort or the validation cohort. A nomogram was established based on the univariate and multivariate logistic regression models using the training cohort. Cox proportional hazards regression models were applied to identify the prognostic factors in univariate and multivariable analyses. Results: Three variables-tumor size, grade, and T stage-were derived from the multivariate analyses in the training cohort and incorporated into the nomogram. The AUC of the nomogram was 0.732 in the training cohort and 0.706 in the validation cohort. There were significant differences in survival among patients with different degrees of LN metastasis risk (training cohort: five-year disease-specific survival (DSS): low risk 88.1% vs. moderate risk 80.0% vs. high risk 72.9%, P < 0.001; validation cohort five-year DSS: low risk 89.0% vs. moderate risk 84.3% vs. high risk 72.2%, P < 0.001). The LN metastasis risk assessed from the model was also an independent prognostic factor. Conclusion: We established a nomogram that accurately predicts LN metastasis risk for elderly patients with EGC before endoscopic resection to avoid further injury from reoperation.

20.
Front Oncol ; 11: 554779, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33718128

RESUMEN

BACKGROUND: Gastric cancer (GC) is a major public health problem worldwide. In recent decades, the treatment of gastric cancer has improved greatly, but basic research and clinical application of gastric cancer remain challenges due to the high heterogeneity. Here, we provide new insights for identifying prognostic models of GC. METHODS: We obtained the gene expression profiles of GSE62254 containing 300 samples for training. GSE15459 and TCGA-STAD for validation, which contain 200 and 375 samples, respectively. Weighted gene co-expression network analysis (WGCNA) was used to identify gene modules. We performed Lasso regression and Cox regression analyses to identify the most significant five genes to develop a novel prognostic model. And we selected two representative genes within the model for immunohistochemistry staining with 105 GC specimens from our hospital to verify the prediction efficiency. Moreover, we estimated the correlation coefficient between our model and immune infiltration using the CIBERSORT algorithm. The data from GSE15459 and TCGA cohort validated the robustness and predictive accuracy of this prognostic model. RESULTS: Of the 12 gene modules identified, 1,198 green-yellow module genes were selected for further analysis. Multivariate Cox analysis was performed on genes from univariate Cox regression and Lasso regression analysis using the Cox proportional hazards regression model. Finally, we constructed a five gene prognostic model: Risk Score = [(-0.7547) * Expression (ARHGAP32)] + [(-0.8272) * Expression (KLF5)] + [1.09 * Expression (MAMLD1)] + [0.5174 * Expression (MATN3)] + [1.66 * Expression (NES)]. The prognosis of samples in the high-risk group was significantly poorer than that of samples in the low-risk group (p = 6.503e-11). The risk model was also regarded as an independent predictor of prognosis (HR, 1.678, p < 0.001). The observed correlation with immune cells suggested that this risk model could potentially predict immune infiltration. CONCLUSION: This study identified a potential risk model for prognosis and immune infiltration prediction in GC using WGCNA and Cox regression analysis.

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