Streptococcus suis serotype 4: a population with the potential pathogenicity in humans and pigs.

Streptococcus suis is a major bacterial pathogen in pigs and an emerging zoonotic pathogen. Different S. suis serotypes exhibit diverse characteristics in population structure and pathogenicity. Surveillance data highlight the significance of S. suis serotype 4 (SS4) in swine streptococcusis, a pathotype causing human infections. However, except for a few epidemiologic studies, the information on SS4 remains limited. In this study, we investigated the population structure, pathogenicity, and antimicrobial characteristics of SS4 based on 126 isolates, including one from a patient with septicemia. We discovered significant diversities within this population, clustering into six minimum core genome (MCG) groups (1, 2, 3, 4, 7-2, and 7-3) and five lineages. Two main clonal complexes (CCs), CC17 and CC94, belong to MCG groups 1 and 3, respectively. Numerous important putative virulence-associated genes are present in these two MCG groups, and 35.00% (7/20) of pig isolates from CC17, CC94, and CC839 (also belonging to MCG group 3) were highly virulent (mortality rate ≥ 80%) in zebrafish and mice, similar to the human isolate ID36054. Cytotoxicity assays showed that the human and pig isolates of SS4 strains exhibit significant cytotoxicity to human cells. Antimicrobial susceptibility testing showed that 95.83% of strains isolated from our labs were classified as multidrug-resistant. Prophages were identified as the primary vehicle for antibiotic resistance genes. Our study demonstrates the public health threat posed by SS4, expanding the understanding of SS4 population structure and pathogenicity characteristics and providing valuable information for its surveillance and prevention.

Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors primarily affecting individuals over the age of 50 years. Recent studies have suggested that the dysbiosis of the gut microbiota, a community of microorganisms in the human gut, is closely associated with the occurrence and development of CRC. Additionally, inflammatory factors (IFs) have also been reported to play a significant role in the development of CRC. However, the causal relationships between the gut microbiota, IFs, and CRC remain unclear. Methods: In this study, we performed Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data to explore the causal relationship between the gut microbiota, IFs, and CRC. The gut microbiota GWAS data were obtained from the MiBioGen study, while the IFs GWAS data were derived from the comprehensive analysis of three independent cohorts. Causal relationship analysis was conducted using appropriate instrumental variables (IVs) and statistical models. Results: MR analysis of the gut microbiota and CRC revealed a negative correlation between the Lachnospiraceae species in the gut and CRC risk, while a positive correlation was observed between Porphyromonadaceae species, Lachnospiraceae UCG010 genus, Lachnospira genus, and Sellimonas genus in the gut, and CRC risk. Additionally, we observed a causal relationship between IL-10 and CRC risk. These findings suggest that the dysbiosis of the gut microbiota might be associated with an increased risk of CRC and that specific bacterial groups may play a crucial role in the occurrence and development of CRC. Conclusion: Using MR analysis, this study revealed the causal relationships between the gut microbiota, IFs, and CRC. The negative correlation between the Lachnospiraceae species in the gut and CRC risk, as well as the causal relationship between IL-10 and CRC, provide important clues for the potential roles of gut microbiota regulation and inflammatory factor control in the prevention and treatment of CRC.

Investigation of genomic and pathogenicity characteristics of Streptococcus suis ST1 human strains from Guangxi Zhuang Autonomous Region (GX) between 2005 and 2020 in China.

Streptococcus suis is a significant and emerging zoonotic pathogen. ST1 and ST7 strains are the primary agents responsible for S. suis human infections in China, including the Guangxi Zhuang Autonomous Region (GX). To enhance our understanding of S. suis ST1 population characteristics, we conducted an investigation into the phylogenetic structure, genomic features, and virulence levels of 73 S. suis ST1 human strains from GX between 2005 and 2020. The ST1 GX strains were categorized into three lineages in phylogenetic analysis. Sub-lineage 3-1a exhibited a closer phylogenetic relationship with the ST7 epidemic strain SC84. The strains from lineage 3 predominantly harboured 89K-like pathogenicity islands (PAIs) which were categorized into four clades based on sequence alignment. The acquirement of 89K-like PAIs increased the antibiotic resistance and pathogenicity of corresponding transconjugants. We observed significant diversity in virulence levels among the 37 representative ST1 GX strains, that were classified as follows: epidemic (E)/highly virulent (HV) (32.4%, 12/37), virulent plus (V+) (29.7%, 11/37), virulent (V) (18.9%, 7/37), and lowly virulent (LV) (18.9%, 7/37) strains based on survival curves and mortality rates at different time points in C57BL/6 mice following infection. The E/HV strains were characterized by the overproduction of tumour necrosis factor (TNF)-α in serum and promptly established infection at the early phase of infection. Our research offers novel insights into the population structure, evolution, genomic features, and pathogenicity of ST1 strains. Our data also indicates the importance of establishing a scheme for characterizing and subtyping the virulence levels of S. suis strains.

Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence.

We conducted a proteomic analysis using mass spectrometry to identify and validate protein biomarkers for accurately predicting recurrence risk in gastrointestinal stromal tumors (GIST) patients, focusing on differentially expressed proteins in metastatic versus primary GIST tissues. We selected five biomarkers-GPX4, RBM4, TPM3, PFKFB2, and PGAM5-and validated their expressions in primary tumors of recurrent and non-recurrent GIST patients via immunohistochemistry. Our analysis of the association between these biomarkers with recurrence-free survival (RFS) and overall survival (OS), along with their interrelationships, revealed that immunohistochemistry confirmed significantly higher expressions of these biomarkers in primary GIST tissues of recurrent patients. Kaplan-Meier survival analysis showed that high expressions of GPX4, RBM4, TPM3, PFKFB2, and PGAM5 correlated with lower RFS, and GPX4 and RBM4 with lower OS. All biomarker pairs showed positive associations, with high expressions correlating with increased recurrence rates, and GPX4 and RBM4 with higher mortality rates. In conclusion, the biomarkers GPX4, RBM4, TPM3, PFKFB2, and PGAM5 are clinically relevant for predicting GIST recurrence, with their high expressions in primary tumors linked to poorer RFS and OS. They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.

Integrated analysis of disulfidptosis-related immune genes signature to boost the efficacy of prognostic prediction in gastric cancer.

BACKGROUND: Gastric cancer (GC) remains a malignant tumor with high morbidity and mortality, accounting for approximately 1,080,000 diagnosed cases and 770,000 deaths worldwide annually. Disulfidptosis, characterized by the stress-induced abnormal accumulation of disulfide, is a recently identified form of programmed cell death. Substantial studies have demonstrated the significant influence of immune clearance on tumor progression. Therefore, we aimed to explore the intrinsic correlations between disulfidptosis and immune-related genes (IRGs) in GC, as well as the potential value of disulfidptosis-related immune genes (DRIGs) as biomarkers. METHODS: This study incorporated the single-cell RNA sequencing (scRNA-seq) dataset GSE183904 and transcriptome RNA sequencing of GC from the TCGA database. Disulfidptosis-related genes (DRGs) and IRGs were derived from the representative literature on both cell disulfidptosis and immunity. The expression and distribution of DRGs were investigated at the single-cell level in different GC cell types. Pearson correlation analysis was used to identify the IRGs closely related to disulfidptosis. The prognostic signature of DRIGs was established using Cox and LASSO analyses. We then analyzed and evaluated the differences in long-term prognosis, Gene Set Enrichment Analysis (GSEA), immune infiltration, mutation profile, CD274 expression, and response to chemotherapeutic drugs between the two groups. A tissue array containing 63 paired GC specimens was used to verify the expression of 4 DRIGs and disulfidptosis regulator SLC7A11 through immunohistochemistry staining. RESULTS: The scRNA-seq analysis found that SLC7A11, SLC3A2, RPN1 and NCKAP1 were enriched in specific cell types and closely related to immune infiltration. Four DIRGs (GLA, HIF-1α, VPS35 and CDC37) were successfully identified to establish a signature to potently predict the survival time of GC patients. Patients with high risk scores generally experienced worse prognoses and exhibited greater resistant to classical chemotherapy drugs. Furthermore, the expression of GLA, HIF-1α, VPS35, CDC37 and SLC7A11 were elevated in GC tissues. A high expression of GLA, HIF-1α, VPS35 or CDC37 was associated with more advanced clinical stage of GC and increased SLC7A11 expression. CONCLUSION: Current study first highlights the potential value of DRIGs as biomarkers in GC. We successfully constructed a robust model incorporating four DRIGs to accurately predict the survival time and clinicopathological characteristics of GC patients.

The clustering status of detached gastric cancer cells inhibits anoikis-induced ferroptosis to promote metastatic colonization.

BACKGROUND AND PURPOSE: Ferroptosis is a form of regulated cell death characterized by iron-dependent lipid peroxidation. Its role in cancer metastasis remains unclear. In this study, we aimed to investigate the potential involvement of ferroptosis in gastric cancer (GC) metastasis. METHODS: GC cells (AGS, MKN45, HGC27) were used to explore the role of ferroptosis in single and clustered cells with extracellular matrix (ECM) detachment in vitro. We overexpressed glutathione peroxidase 4 (GPX4) to inhibit ferroptosis and assessed the changes in cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Then tumor tissues from 54 GC patients with and without lymphatic metastasis were collected for immunohistochemical staining to investigate the expression of ferroptosis and EMT markers. Finally, Kaplan-Meier survival curves were used to investigate the relationship between overall survival and expression of GPX4 in 178 GC patients. RESULTS: Detached single cells had lower viability than adherent cells, but cell clustering improved their survival under matrix-detached conditions. Detached single cells exhibited an induction of iron-dependent reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, lipid peroxidation, upregulation of ACSL4, TFRC and HO-1, increased iron levels, and changes in mitochondrial morphology. Opposite effects were observed in detached clustered cells, including the upregulation of the ferroptosis suppressors GPX4 and SLC7A11. Overexpression of GPX4 inhibited ferroptosis and promoted GC cell proliferation, migration, invasion, and EMT. Immunohistochemical analysis of tumor tissues from GC patients indicated that lymphatic metastasis was associated with higher potential for ferroptosis inhibition and EMT induction. Finally, Kaplan-Meier survival curves demonstrated a significant decrease in overall survival among GC patients with high GPX4 expression. CONCLUSIONS: Our study provides the first evidence that inhibition of ferroptosis is a crucial mechanism promoting GC metastasis. GPX4 may be a valuable prognostic factor for GC patients. These findings suggest that targeting ferroptosis inhibition may be a promising strategy for GC patients with metastatic potential. Trial registration The ethical approval code of this study in Institutional Review Board of Peking Union Medical College Hospital is No: K1447.

Comprehensive integration of single-cell RNA and transcriptome RNA sequencing to establish a pyroptosis-related signature for improving prognostic prediction of gastric cancer.

Cell pyroptosis, a Gasdermin-dependent programmed cell death characterized by inflammasome, plays a complex and dynamic role in Gastric cancer (GC), a serious threat to human health. Therefore, the value of pyroptosis-related genes (PRGs) as prognostic biomarkers and therapeutic indicators for patients needs to be exploited in GC. This study integrates single-cell RNA sequencing (scRNA-seq) dataset GSE183904 with GC transcriptome data from the TCGA database, focusing on the expression and distribution of PRGs in GC at the single-cell level. The prognostic signature of PRGs was established by using Cox and LASSO analyses. The differences in long-term prognosis, immune infiltration, mutation profile, CD274 and response to chemotherapeutic drugs between the two groups were analyzed and evaluated. A tissue array was used to verify the expression of six PRGs, CD274, CD163 and FoxP3. C12orf75, VCAN, RGS2, MKNK2, SOCS3 and TNFAIP2 were successfully screened out to establish a signature to potently predict the survival time of GC patients. A webserver (https://pumc.shinyapps.io/GastricCancer/) for prognostic prediction in GC patients was developed based on this signature. High-risk score patients typically had worse prognoses, resistance to classical chemotherapy, and a more immunosuppressive tumor microenvironment. VCAN, TNFAIP2 and SOCS3 were greatly elevated in the GC while RGS2 and MKNK2 were decreased in the tumor samples. Further, VCAN was positively related to the infiltrations of Tregs and M2 TAMs in GC TME and the CD274 in tumor cells. In summary, a potent pyroptosis-related signature was established to accurately forecast the survival time and treatment responsiveness of GC patients.

Perioperative Enteral Immunonutrition Support for the Immune Function and Intestinal Mucosal Barrier in Gastric Cancer Patients Undergoing Gastrectomy: A Prospective Randomized Controlled Study.

OBJECTIVE: The impact of perioperative immunonutrition on patients undergoing radical gastrectomy remains undetermined. This study aimed to assess the influence of enteral immunonutrition support on postoperative immune function and intestinal mucosal barrier function following radical gastrectomy, contrasting findings with a control group to furnish evidence for perioperative enteral nutrition support. METHODS: In this prospective randomized trial, 65 patients who underwent radical gastrectomy between June 2022 and June 2023 were included. Participants were allocated to either the study group (receiving enteral immunonutrition) or the control group (not receiving enteral immunonutrition). We compared postoperative rehabilitation and complications between the groups, analyzed the intestinal mucosal barrier function markers on the 3rd and 7th postoperative days, and delved deeper into peripheral blood cell immunity, inflammation, and nutritional indicators. RESULTS: The cohort consisted of 30 patients in the study group and 35 in the control group, with no significant differences in demographic attributes between the two groups. On the 3rd postoperative day, the diamine oxidase, D-lactic acid, and endotoxin levels in the study group were significantly lower than those in the control group (p = 0.029, p = 0.044, and p = 0.010, respectively). By the 7th postoperative day, these levels continued to be significantly diminished in the study group (p = 0.013, p = 0.033, and p = 0.004, respectively). The times to first flatus (p = 0.012) and first bowel movement (p = 0.012) were significantly shorter in the study group. Moreover, postoperative complications in the study group were fewer than in the control group (p = 0.039). On the 7th postoperative day, the study group had lower peripheral white blood cell (WBC) levels (p = 0.020) and neutrophil-lymphocyte ratios (NLR) (p = 0.031), but displayed elevated albumin levels (p = 0.006). One month post-surgery, the CD4+T and CD8+T counts were significantly greater in the study group (p = 0.003 and p = 0.012, respectively). Correlation analyses indicated that NLR and complications were associated with endotoxin levels. CONCLUSION: Administering perioperative enteral immunonutrition enhances postoperative immune and intestinal mucosal barrier functions in patients undergoing radical gastrectomy. This effect leads to diminished inflammatory responses, a decreased rate of postoperative complications, and accelerated patient recovery.

Perioperative chemotherapy versus adjuvant chemotherapy treatment for resectable locally advanced gastric cancer: a retrospective cohort study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced gastric cancer (LAGC), but the clinical safety and efficacy are still controversial. This study aims to compare perioperative chemotherapy (PEC) with adjuvant chemotherapy (AC) for resectable LAGC. METHODS: Patients who underwent D2 gastrectomy for resectable LAGC were retrospectively reviewed, and divided into NSA group (NAC plus surgery and AC) and SA group (surgery followed by AC). The baseline characteristics and perioperative data were compared. Survival analysis was based on Kaplan-Meier method. Multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: A total of 450 patients were eligible for this study. 218 patients received NAC plus surgery and AC, while 232 upfront surgery followed by AC. The baseline characteristics were comparable between the two groups. NSA group showed significant superiority in R0 resection rate (P = 0.014), excised tumor size (P = 0.038), and tumor downstage (all P < 0.001). NAC did not affect postoperative complications or AC-related grade 3/4 adverse events. Patients in NSA group achieved significantly longer OS (P = 0.021) and DFS (P = 0.002). The Cox regression model showed that NAC was independently associated with better OS (HR 0.245, P = 0.039) and DFS (HR 0.591, P = 0.031). CONCLUSIONS: Compared with SA, the administration of NSA was considered safe and feasible for achieving higher R0 resection rate without increasing the postoperative complications or AC-related grade 3/4 adverse events, and NAC was independently associated with better OS and DFS for resectable LAGC.

Tumour-associated macrophages in gastric cancer: From function and mechanism to application.

BACKGROUND: Gastric cancer (GC) is a malignant tumour, with high morbidity and mortality rates worldwide. The occurrence and development of GC is a complex process involving genetic changes in tumour cells and the influence of the surrounding tumour microenvironment (TME). Accumulative evidence shows that tumour-associated macrophages (TAMs) play a vital role in GC, acting as plentiful and active infiltrating inflammatory cells in the TME. MAIN BODY: In this review, the different functions and mechanisms of TAMs in GC progression, including the conversion of phenotypic subtypes; promotion of tumour proliferation, invasion and migration; induction of chemoresistance; promotion of angiogenesis; modulation of immunosuppression; reprogramming of metabolism; and interaction with the microbial community are summarised. Although the role of TAMs in GC remains controversial in clinical settings, clarifying their significance in the treatment selection and prognostic prediction of GC could support optimising TAM-centred clinicaltherapy. CONCLUSION: In summary, we reviewed the the phenotypic polarisation, function and molecular mechanism of TAMs and their potential applications in the treatment selection and prognostic prediction of GC.

Comparison of the predictive value of pathological response at primary tumor and lymph node status after neoadjuvant chemotherapy in locally advanced gastric cancer

Background Preoperative chemotherapy has been increasingly used in locally advanced gastric cancer (LAGC). However, the prognostic factors are still insufficient. This study aimed to investigate the prognostic significance of pathological response of the primary tumor to neoadjuvant chemotherapy (NACT) and the lymph node status after NACT. Methods Data from 160 patients with LAGC treated with NACT followed by gastrectomy and met the inclusion criteria between March 2016 and December 2019 were retrospectively reviewed. Pathological evaluation after NACT was based on the grade of pathological response of the primary tumor and the status of lymph node. Survival curves for overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan–Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. Results Among 160 selected cases, 90 had pathological response (PR), while 70 had no pathological response (nPR) to NACT. Smaller tumor size was presented in PR group, which also had lower level of signet ring cell features, compared to nPR group (all p < 0.05). Based on the status of lymph nodes, nodal status (−) group showed smaller tumor size, lower depth of tumor invasion, better differentiated degree, lower level of signet ring cell features, lower rate of lymphatic and venous invasion and less advanced ypTNM stage (all p < 0.05). Survival was equivalent between PR and nPR group (all p > 0.05), while patients with no lymph node metastasis had better DFS than that with lymph node metastasis (HR 0.301, 95% CI 0.194–0.468, p = 0.002) (AU)

Comprehensive analysis of cuproptosis-related immune biomarker signature to enhance prognostic accuracy in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a malignant tumor with high prevalence and fatality. Cuproptosis is a recently identified copper-dependent programmed cell death mechanism. Multiple studies have demonstrated the profound impact of the immune microenvironment on tumor development. Hence, we decided to excavate the potential functional roles of cuproptosis-related immune genes (CRIGs) in GC and their values as biomarkers. METHODS: Cuproptosis- and immune-related genes were curated from top published studies on cell cuproptosis and cellular immunity. Transcriptome data and clinical information were obtained from TCGA, GTEx, and GEO databases. Cox and LASSO analyses were used to establish a prognostic signature for GC. Long-term prognosis, immune infiltration, immune checkpoint, and drug response were compared between signature groups. CRIG expression in GC scRNA-seq was analyzed. Immunohistochemistry was used to evaluate CRIG and cuproptosis regulator FDX1 in GC tissues. RESULTS: Seven CRIGs (ANOS1, CTLA4, ITGAV, CXCR4, NRP1, FABP3, and LGR6) were selected to establish a potent signature to forecast the long-term prognosis of patients. GC patients had worse prognosis and poor responses to chemotherapeutic drugs (5-Fluorouracil and paclitaxel) in the high-risk group. scRNA-seq revealed that CTLA4, ITGAV, CXCR4, and NRP1 enrichment in specific cell types regulated the progression of GC. Moreover, NRP1, CXCR4, LGR6, CTLA4, and FDX1 were elevated in GC tissues, with a positive correlation between their expression and FDX1. CONCLUSIONS: To conclude, this study first provides insights into the functions of CRIGs in GC. Furthermore, a robust cuproptosis-related immune biomarker signature was established to forecast the long-term survival of GC patients accurately.

Comparison of the predictive value of pathological response at primary tumor and lymph node status after neoadjuvant chemotherapy in locally advanced gastric cancer.

BACKGROUND: Preoperative chemotherapy has been increasingly used in locally advanced gastric cancer (LAGC). However, the prognostic factors are still insufficient. This study aimed to investigate the prognostic significance of pathological response of the primary tumor to neoadjuvant chemotherapy (NACT) and the lymph node status after NACT. METHODS: Data from 160 patients with LAGC treated with NACT followed by gastrectomy and met the inclusion criteria between March 2016 and December 2019 were retrospectively reviewed. Pathological evaluation after NACT was based on the grade of pathological response of the primary tumor and the status of lymph node. Survival curves for overall survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: Among 160 selected cases, 90 had pathological response (PR), while 70 had no pathological response (nPR) to NACT. Smaller tumor size was presented in PR group, which also had lower level of signet ring cell features, compared to nPR group (all p < 0.05). Based on the status of lymph nodes, nodal status (-) group showed smaller tumor size, lower depth of tumor invasion, better differentiated degree, lower level of signet ring cell features, lower rate of lymphatic and venous invasion and less advanced ypTNM stage (all p < 0.05). Survival was equivalent between PR and nPR group (all p > 0.05), while patients with no lymph node metastasis had better DFS than that with lymph node metastasis (HR 0.301, 95% CI 0.194-0.468, p = 0.002). Multivariable Cox regression analysis identified that lymph node status after NACT was an independent prognostic factor associated with survival (OS: hazard ratio 1.756, 95% CI 1.114-3.278, p = 0.029; DFS: hazard ratio 1.901, 95% CI 1.331-3.093, p = 0.012). CONCLUSION: Lymph node status is a potential independent prognostic factor for LAGC patients treated with NACT and may be more efficient than pathological response in primary tumor.

Integrated analysis from multicentre studies identities m7G-related lncRNA-derived molecular subtypes and risk stratification systems for gastric cancer.

Introduction: Gastric cancer (GC) is the fourth leading cause of cancer death worldwide. Due to the lack of effective chemotherapy methods for advanced gastric cancer and poor prognosis, the emergence of immunotherapy has brought new hope to gastric cancer. Further research is needed to improve the response rate to immunotherapy and identify the populations with potential benefits of immunotherapy. It is unclear whether m7G-related lncRNAs influence tumour immunity and the prognosis of immunotherapy. Methods: This study evaluated 29 types of immune cells and immune functions in gastric cancer patients, and m7G-related lncRNAs and their molecular subtypes were identified. In addition, we also studied the biological function characteristics of m7G-related lncRNA molecular subtypes. Finally, the patient's risk score was calculated based on m7G-related lncRNAs, and a nomogram of staging and risk groups was established to predict the prognosis. For experimental verification, RT-qPCR were preformed from the native cohort. Results: After identifying m7G-related lncRNAs and their molecular subtypes, we found three molecular subtypes, the B subtype had the highest level of infiltration, and the B subtype may benefit more from immunotherapy. We divided GC patients into two regulator subtypes based on biological function. The two subtypes have significant immunological differences and can be used to judge ICI treatment. We established a risk score formula based on five lncRNAs, including LINC00924, LINC00944, LINC00865, LINC00702, and ZFAS1. Patients with poor prognoses were closely related to patients in the high-risk group. After comprehensive analysis of different risk groups, the efficacy of the high-risk group on bleomycin, cisplatin, docetaxel, doxorubicin and etoposide was better than that of the low-risk group, suggesting that risk subgroups based on risk scores play a guiding role in chemotherapy and that the high-risk group may benefit more from immunotherapy. RT-qPCR results showed that LINC00924, LINC00944, and LINC00865 were highly expressed in tumour tissues, while LINC00702 and ZFAS1 were expressed at low levels in tumour tissues. Discussion: In conclusion, we were the first to discover that m7G-related lncRNAs play a vital role in the tumour immune microenvironment of gastric cancer, and a risk prediction model was established to identify patients with potential benefits from immunotherapy and predict the prognosis of GC patients.

Comparisons of nutritional status and complications between patients with and without postoperative feeding jejunostomy tube in gastric cancer: a retrospective study.

Background: Feeding jejunostomy tube (FJT) enables early postoperative nutritional supply for gastric cancer patients undergoing surgery. However, the nutritional benefit of FJT may be accompanied by potential risk of increased complications, so both the nutritional improvement and the complication rates associated with FJT should be assessed. Methods: From January 2009 to December 2014, 715 consecutive patients underwent gastric cancer resection at the Peking Union Medical College Hospital in China. The perioperative nutritional index and incidence of complications in patients with FJT placement were retrospectively compared to those in patients without FJT placement. Nutritional data including albumin, prealbumin, hemoglobin, and high sensitivity C-reactive protein, the neutrophil-to-lymphocyte ratio (NLR), and Onodera's prognostic nutrition index (OPNI) were recorded at the following 3 timepoints: preoperatively, 1-week postoperatively, and 1-month postoperatively. Postoperative complications including surgical site infection, intra-abdominal infections, anastomotic leaks and gastroparesis were assessed. Multivariate logistic regression was used to study the association between FJT and complications. Results: A total of 715 patients were included in the study. The mean age was 60.4 years and 72.2% were male. The overall characteristics between FJT and no-FJT groups were comparable. Of the 247 total gastrectomy cases, 98 (39.7%) had a FJT placed. Compared to the total gastrectomy patients without a FJT, the 98 patients with a FJT had a lower hemoglobin level (P=0.048) and NLR (P=0.030) preoperatively, and higher albumin (P=0.005), prealbumin (P<0.001), and hemoglobin (P=0.014) levels, a higher OPNI (P=0.027), and a lower NLR (P=0.005) 1-month postoperatively. Of the 468 subtotal gastrectomy cases, 87 (18.6%) had a FJT placed. Compared to the subtotal gastrectomy patients without a FJT, these 87 patients had a lower NLR (P=0.006) 1-week postoperatively, and a higher albumin level (P=0.009) 1-month postoperatively. In the multivariate analysis, FJT placement was not associated with postoperative adverse outcomes, including surgical site infection [odds ratio (OR) =1.21, P=0.79], intra-abdominal infection (OR =0.38, P=0.11), anastomotic leak (OR =0.58, P=0.53), reoperation (OR =0.22, P=0.23), gastroparesis (OR =6.35, P=0.08), or hospitalization for more than 30 days (OR =0.58, P=0.32). Conclusions: Early enteral nutritional support by FJT after gastrectomy tended to improve the nutritional status of patients, while it did not appear to increase the incidence rate of postoperative complications.

Association between Plasma FGF21 Levels and Body Composition in Patients with Gastric Cancer.

BACKGROUND: Accumulating evidence has suggested that Fibroblast growth factor 21 (FGF21) plays an important role in metabolic diseases. This study aimed to investigate the relationship between plasma FGF21 levels and body composition parameters in gastric cancer (GC) patients. METHODS: This study was cross-sectional based on a prospective cohort of GC patients in a single center. Computer tomography (CT) and bioelectrical impedance analysis (BIA) were used to estimate skeletal muscle and adipose tissue mass. Blood samples were collected and plasma concentrations of FGF21 were measured by ELISA. Spearman's rank correlation test and logistic regression analysis were performed to assess associations between plasma FGF21 levels and these body composition parameters. RESULTS: A total of 66 GC patients were enrolled in this study. Plasma FGF21 levels were significantly higher in women compared with men. The plasma FGF21 levels were positively correlated with fat mass index (FMI), fat mass percentage (FM%), and subcutaneous adipose tissue index (SATI). Furthermore, after adjustment for confounders, the lower plasma FGF21 levels were remain associated with increased odds for low SATI. CONCLUSIONS: Plasma FGF21 levels were positively associated with FMI, FM%, and SATI in GC patients, suggesting a potential mechanistic link between FGF21 and subcutaneous adipose tissue in GC.

Visceral Adipose Tissue Assessment Enhances the Prognostic Value of GLIM Criteria in Patients with Gastric Cancer Undergoing Radical Gastrectomy after Neoadjuvant Treatment.

BACKGROUND: The Global Leadership Initiative on Malnutrition (GLIM) criteria has been recently published for diagnosing malnutrition in adults. However, the validity of the GLIM criteria has not been well-established in patients with gastric cancer (GC) treated with neoadjuvant treatment (NT) followed by radical gastrectomy. The present study aimed to explore the prognostic value of GLIM-defined malnutrition before NT and after NT in GC patients and to investigate whether additional visceral adipose tissue (VAT) assessment could improve the predictive power of the GLIM criteria for NT-related adverse events (AEs) and long-term survival. METHODS: GC patients who underwent radical surgery after NT from June 2016 to June 2020 were enrolled in this study. The cross-sectional areas of total skeletal muscle (TSM) and VAT were measured using computed tomography (CT) before NT and after NT. GLIM-defined malnutrition was diagnosed using the two-step approach, including nutritional risk screening and diagnostic assessment. Low VAT was also added to the diagnosis of malnutrition in this study. The predictive value of these malnutrition diagnoses for NT-related AEs, and long-term survival was evaluated in GC patients. RESULTS: A total of 182 GC patients were included in this study, of which 66 (36.3%) patients before NT and 55 (30.2%) patients after NT were diagnosed with GLIM-defined malnutrition, respectively. In addition to GLIM-defined malnutrition, 54 (29.7%) patients had additional low VAT before NT, and 39 (21.4%) patients had additional low VAT after NT. GLIM-defined malnutrition alone before NT was not associated with NT-related AEs in GC patients. The addition of low VAT to GLIM-defined malnutrition led to a significant predictive value for NT-related AEs. Furthermore, GLIM-defined malnutrition before NT and after NT were both identified as independent risk factors for overall survival (OS) and disease-free survival (DFS). The combination of low VAT and GLIM-defined malnutrition showed a higher hazard ratio for the prediction of OS and DFS both before NT and after NT. CONCLUSIONS: The addition of VAT assessment using CT improved the predictive value of GLIM-defined malnutrition for NT-related AEs and long-term survival in GC patients treated with NT followed by radical gastrectomy, which further supports the prognostic importance of assessing adipose tissue simultaneously during the routine nutritional assessment in patients with cancer.

Does postoperative chemotherapy improve overall survival of patients with ypT1-2N0 cancer?

BACKGROUND: Perioperative chemotherapy combined with curative gastrectomy has been increasingly represented the standard therapeutic strategy for resectable gastric cancer (GC). However, it is still unclear whether postoperative chemotherapy has a survival benefit for ypT1-2N0 gastric cancer patients who have undergone preoperative chemotherapy followed curative gastrectomy. METHODS: The data of patients who undergone neoadjuvant chemotherapy followed by gastrectomy and had pathological classification of ypT1-2N0 between March 2016 and December 2020 at Peking Union Medical College Hospital were retrospectively reviewed. Chi-square test was adopted to compare the difference between the patients with postoperative chemotherapy (pCHT) and without postoperative chemotherapy (no pCHT). Survival curves for overall survival (OS) were estimated using the Kaplan-Meier method, and the log-rank test was used to compare survival difference. Univariate and multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: A total of 134 patients met the inclusion criteria and 56 (41.8%) of them have undergone postoperative chemotherapy. There were no statistically significant differences in demographic and clinicopathologic characteristics between pCHT group and no pCHT group (all p > 0.05). Postoperative chemotherapy was not associated with a significant improvement in overall survival (OS) (Hazard ratio [HR] 0.815, 95% confidence interval [CI] 0.403-1.650; p = 0.474). Subgroup analyses demonstrated survival was equivalent between pCHT and no CHT group in ypT1N0 patients (HR 0.832, CI 0.222-3.121; p = 0.786) and ypT2N0 patients (HR 1.284, CI 0.564-2.924; p = 0.551). Multivariable analysis identified that clinical T stage independently influenced prognosis (cT3 vs. cT2: HR 2.875, 95% CI 0.998-8.281, p = 0.050; cT4 vs. cT2: HR 7.382, 95% CI 2.569-21.211, p < 0.001). In clinical T3-4 patients, there was an overall survival benefit for postoperative chemotherapy (HR 0.270, 95% CI 0.114-0.634; p = 0.006). No survival benefit of postoperative chemotherapy was identified in clinical T2 patients (HR 0.689, 95% CI 0.200-2.372; p = 0.579). Furthermore, postoperative chemotherapy was proved to be an independently positive prognostic factor for clinical T3-4 patients (HR 0.132, 95% CI 0.051-0.345; p < 0.001). CONCLUSION: Postoperative chemotherapy might offer survival benefit to patients with ypT1-2N0 gastric cancer whose clinical T stage was T3-4 before preoperative chemotherapy.

Risk factors for cancer-specific survival in elderly gastric cancer patients after curative gastrectomy.

BACKGROUND/OBJECTIVES: This study aimed to investigate cancer-specific survival (CSS) and associated risk factors in elderly gastric cancer (EGC) patients. SUBJECTS/METHODS: EGC patients (≥ 70 yrs) who underwent curative gastrectomy between January 2013 and December 2017 at our hospital were included. Clinicopathologic characteristics and survival data were collected. Receiver operating characteristic (ROC) analysis was used to extract the best cutoff point for body mass index (BMI). A Cox proportional hazards model was used to determine the risk factors for CSS. RESULTS: In total, 290 EGC patients were included, with a median age of 74.7 yrs. The median follow-up time was 31 (1-77) mon. The postoperative 1-yr, 3-yr and 5-yr CSS rates were 93.7%, 75.9% and 65.1%, respectively. Univariate analysis revealed risk factors for CSS, including age (hazard ratio [HR] = 1.08; 95% confidence interval [CI], 1.01-1.15), intensive care unit (ICU) admission (HR = 1.73; 95% CI, 1.08-2.79), nutritional risk screening (NRS 2002) score ≥ 5 (HR = 2.33; 95% CI, 1.49-3.75), and preoperative prognostic nutrition index score < 45 (HR = 2.06; 95% CI, 1.27-3.33). The ROC curve showed that the best BMI cutoff value was 20.6 kg/m2. Multivariate analysis indicated that a BMI ≤ 20.6 kg/m2 (HR = 2.30; 95% CI, 1.36-3.87), ICU admission (HR = 1.97; 95% CI, 1.17-3.30) and TNM stage (stage II: HR = 5.56; 95% CI, 1.59-19.43; stage III: HR = 16.20; 95% CI, 4.99-52.59) were significantly associated with CSS. CONCLUSIONS: Low BMI (≤ 20.6 kg/m2), ICU admission and advanced pathological TNM stages (II and III) are independent risk factors for CSS in EGC patients after curative gastrectomy. Nutrition support, better perioperative management and early diagnosis would be helpful for better survival.