Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers.

BACKGROUND: Gastric cancer (GC) is the fifth most common and the fourth most lethal malignant tumour in the world. Most patients are already in the advanced stage when they are diagnosed, which also leads to poor overall survival. The effect of postoperative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence. AIM: To investigate the safety and efficacy of a programmed cell death 1 (PD-1) inhibitor combined with oxaliplatin and S-1 (SOX) in the treatment of Borrmann large type III and IV GCs. METHODS: A retrospective analysis (IRB-2022-371) was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy (NAT) from January 2020 to December 2021. According to the different neoadjuvant treatment regimens, the patients were divided into the SOX group (61 patients) and the PD-1 + SOX (P-SOX) group (28 patients). RESULTS: The pathological response (tumor regression grade 0/1) in the P-SOX group was significantly higher than that in the SOX group (42.86% vs 18.03%, P = 0.013). The incidence of ypN0 in the P-SOX group was higher than that in the SOX group (39.29% vs 19.67%, P = 0.05). The use of PD-1 inhibitors was an independent factor affecting tumor regression grade. Meanwhile, the use of PD-1 did not increase postoperative complications or the adverse effects of NAT. CONCLUSION: A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

Burdens of stomach and esophageal cancer from 1990 to 2019 and projection to 2030 in China: Findings from the 2019 Global Burden of Disease Study.

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.

Development and validation of nomogram for predicting early recurrence after radical gastrectomy of gastric cancer.

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.

The role of macrophages in gastric cancer.

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.

A predictive model of immune infiltration and prognosis of head and neck squamous cell carcinoma based on cell adhesion-related genes: including molecular biological validation.

Background: Focal adhesion serves as a bridge between tumour cells and the extracellular matrix (ECM) and has multiple roles in tumour invasion, migration, and therapeutic resistance. However, studies on focal adhesion-related genes (FARGs) in head and neck squamous cell carcinoma (HNSCC) are limited. Methods: Data on HNSCC samples were obtained from The Cancer Genome Atlas and GSE41613 datasets, and 199 FARGs were obtained from the Molecular Signatures database. The integrated datasets' dimensions were reduced by the use of cluster analysis, which was also used to classify patients with HNSCC into subclusters. A FARG signature model was developed and utilized to calculate each patient's risk score using least extreme shrinkage and selection operator regression analysis. The risk score was done to quantify the subgroups of all patients. We evaluated the model's value for prognostic prediction, immune infiltration status, and therapeutic response in HNSCC. Preliminary molecular and biological experiments were performed to verify these results. Results: Two different HNSCC molecular subtypes were identified according to FARGs, and patients with C2 had a shorter overall survival (OS) than those with C1. We constructed an FARG signature comprising nine genes. We constructed a FARG signature consisting of nine genes. Patients with higher risk scores calculated from the FARG signature had a lower OS, and the FARG signature was considered an independent prognostic factor for HNSCC in univariate and multivariate analyses. FARGs are associated with immune cell invasion, gene mutation status, and chemosensitivity. Finally, we observed an abnormal overexpression of MAPK9 in HNSCC tissues, and MAPK9 knockdown greatly impeded the proliferation, migration, and invasion of HNSCC cells. Conclusion: The FARG signature can provide reliable prognostic prediction for patients with HNSCC. Apart from that, the genes in this model were related to immune invasion, gene mutation status, and chemosensitivity, which may provide new ideas for targeted therapies for HNSCC.

Efficient plasma metabolic fingerprinting as a novel tool for diagnosis and prognosis of gastric cancer: a large-scale, multicentre study.

OBJECTIVE: Metabolic biomarkers are expected to decode the phenotype of gastric cancer (GC) and lead to high-performance blood tests towards GC diagnosis and prognosis. We attempted to develop diagnostic and prognostic models for GC based on plasma metabolic information. DESIGN: We conducted a large-scale, multicentre study comprising 1944 participants from 7 centres in retrospective cohort and 264 participants in prospective cohort. Discovery and verification phases of diagnostic and prognostic models were conducted in retrospective cohort through machine learning and Cox regression of plasma metabolic fingerprints (PMFs) obtained by nanoparticle-enhanced laser desorption/ionisation-mass spectrometry (NPELDI-MS). Furthermore, the developed diagnostic model was validated in prospective cohort by both NPELDI-MS and ultra-performance liquid chromatography-MS (UPLC-MS). RESULTS: We demonstrated the high throughput, desirable reproducibility and limited centre-specific effects of PMFs obtained through NPELDI-MS. In retrospective cohort, we achieved diagnostic performance with areas under curves (AUCs) of 0.862-0.988 in the discovery (n=1157 from 5 centres) and independent external verification dataset (n=787 from another 2 centres), through 5 different machine learning of PMFs, including neural network, ridge regression, lasso regression, support vector machine and random forest. Further, a metabolic panel consisting of 21 metabolites was constructed and identified for GC diagnosis with AUCs of 0.921-0.971 and 0.907-0.940 in the discovery and verification dataset, respectively. In the prospective study (n=264 from lead centre), both NPELDI-MS and UPLC-MS were applied to detect and validate the metabolic panel, and the diagnostic AUCs were 0.855-0.918 and 0.856-0.916, respectively. Moreover, we constructed a prognosis scoring system for GC in retrospective cohort, which can effectively predict the survival of GC patients. CONCLUSION: We developed and validated diagnostic and prognostic models for GC, which also contribute to advanced metabolic analysis towards diseases, including but not limited to GC.

Glutathione peroxidase 2 knockdown suppresses gastric cancer progression and metastasis via regulation of kynurenine metabolism.

Gastric cancer (GC) is among the most lethal malignancies due to its poor early diagnosis and high metastasis rate, and new therapeutic targets are urgently needed to develop effective anti-GC drugs. Glutathione peroxidase-2 (GPx2) plays various roles in tumor progression and patient survival. Herein, we found that GPx2 was overexpressed and negatively correlated with poor prognosis by using clinical GC samples for validation. GPx2 knockdown suppressed GC proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) in vitro and in vivo. In addition, proteomic analysis revealed that GPx2 expression regulated kynureninase (KYNU)-mediated metabolism. As one of the key proteins involved in tryptophan catabolism, KYNU can degrade the tryptophan metabolite kynurenine (kyn), which is an endogenous ligand for AhR. Next, we revealed that the activation of the reactive oxygen species (ROS)-mediated KYNU-kyn-AhR signaling pathway caused by GPx2 knockdown was involved in GC progression and metastasis. In conclusion, our results showed that GPx2 acted as an oncogene in GC and that GPx2 knockdown suppressed GC progression and metastasis by suppressing the KYNU-kyn-AhR signaling pathway, which was caused by the accumulation of ROS.

Deep learning radio-clinical signatures for predicting neoadjuvant chemotherapy response and prognosis from pretreatment CT images of locally advanced gastric cancer patients.

BACKGROUND: Early noninvasive screening of patients who would benefit from neoadjuvant chemotherapy (NCT) is essential for personalized treatment of locally advanced gastric cancer (LAGC). The aim of this study was to identify radio-clinical signatures from pretreatment oversampled computed tomography (CT) images to predict the response to NCT and prognosis of LAGC patients. METHODS: LAGC patients were retrospectively recruited from six hospitals from January 2008 to December 2021. An SE-ResNet50-based chemotherapy response prediction system was developed from pretreatment CT images preprocessed with an imaging oversampling method (i.e. DeepSMOTE). Then, the deep learning (DL) signature and clinic-based features were fed into the deep learning radio-clinical signature (DLCS). The predictive performance of the model was evaluated based on discrimination, calibration, and clinical usefulness. An additional model was built to predict overall survival (OS) and explore the survival benefit of the proposed DL signature and clinicopathological characteristics. RESULTS: A total of 1060 LAGC patients were recruited from six hospitals; the training cohort (TC) and internal validation cohort (IVC) patients were randomly selected from center I. An external validation cohort (EVC) of 265 patients from five other centers was also included. The DLCS exhibited excellent performance in predicting the response to NCT in the IVC [area under the curve (AUC), 0.86] and EVC (AUC, 0.82), with good calibration in all cohorts ( P >0.05). Moreover, the DLCS model outperformed the clinical model ( P <0.05). Additionally, we found that the DL signature could serve as an independent factor for prognosis [hazard ratio (HR), 0.828, P =0.004]. The concordance index (C-index), integrated area under the time-dependent ROC curve (iAUC), and integrated Brier score (IBS) for the OS model were 0.64, 1.24, and 0.71 in the test set. CONCLUSION: The authors proposed a DLCS model that combined imaging features with clinical risk factors to accurately predict tumor response and identify the risk of OS in LAGC patients prior to NCT, which can then be used to guide personalized treatment plans with the help of computerized tumor-level characterization.

1-Methyl-4-R-1,2,4-triazolium (R = -CH2CH2OCH3, -CH2COOCH2CH3)-Based Ionic Liquids as Plasticizers for Solid Propellants.

In this paper, a series of energetic ionic liquid plasticizers of 1-methyl-4-methoxyethyl-1,2,4-triazolium chloride (1), 1-methyl-4-methoxyethyl-1,2,4-triazolium bis(trifluoromethylsulfonyl)imide (1a), 1-methyl-4-methoxyethyl-1,2,4-triazolium nitrate (1b), 1-methyl-4-ethyl acetate-1,2,4-triazolium chloride (2), 1-methyl-4-ethyl acetate-1,2,4-triazolium bis(trifluoromethylsulfonyl)imide (2a), and 1-methyl-4-ethyl acetate-1,2,4-triazolium nitrate (2b) were synthesized and characterized. The results show that compounds 1a, 1b, 2a, and 2b have lower melting points (Tm, -72.60 to -32.67 °C) and good thermal stability (Td, 161-348 °C) and are suitable as plasticizers for hydroxyl-terminated polybutadiene (HTPB) curing systems. Among these four ionic liquids, ester-functionalized cations can help to improve the tensile strength (2a, 0.943 MPa; 2b, 1.113 MPa) of the cured system, while ether-functionalized cations are more beneficial to improve elongation at break (1a, 522.90%; 1b, 484.45%). Ester-functionalized ionic liquids are more beneficial to reduce the glass transition temperature of HTPB elastomers. The storage modulus of HTPB elastomers containing NO3- is higher, while that of HTPB elastomers containing NTf2- is lower. The crosslink densities of HTPB/TDI/2a and HTPB/TDI/2b plasticized by ester-functionalized ionic liquids are larger, which are 9369 and 9616 mol/m3, respectively. There are hydrogen bond interactions between the ionic liquid and the HTPB elastomer, and these interactions changed the distribution of the hard and soft segments in the polymer molecules.

Corrigendum: NanoSIMS analysis of water content in bridgmanite at the micron scale: an experimental approach to probe water in Earth's deep mantle.

[This corrects the article DOI: 10.3389/fchem.2023.1166593.].

NanoSIMS analysis of water content in bridgmanite at the micron scale: An experimental approach to probe water in Earth's deep mantle.

Water, in trace amounts, can greatly alter chemical and physical properties of mantle minerals and exert primary control on Earth's dynamics. Quantifying how water is retained and distributed in Earth's deep interior is essential to our understanding of Earth's origin and evolution. While directly sampling Earth's deep interior remains challenging, the experimental technique using laser-heated diamond anvil cell (LH-DAC) is likely the only method available to synthesize and recover analog specimens throughout Earth's lower mantle conditions. The recovered samples, however, are typically of micron sizes and require high spatial resolution to analyze their water abundance. Here we use nano-scale secondary ion mass spectrometry (NanoSIMS) to characterize water content in bridgmanite, the most abundant mineral in Earth's lower mantle. We have established two working standards of natural orthopyroxene that are likely suitable for calibrating water concentration in bridgmanite, i.e., A119(H2O) = 99 ± 13 µg/g (1SD) and A158(H2O) = 293 ± 23 µg/g (1SD). We find that matrix effect among orthopyroxene, olivine, and glass is less than 10%, while that between orthopyroxene and clinopyroxene can be up to 20%. Using our calibration, a bridgmanite synthesized by LH-DAC at 33 ± 1 GPa and 3,690 ± 120 K is measured to contain 1,099 ± 14 µg/g water, with partition coefficient of water between bridgmanite and silicate melt ∼0.025, providing the first measurement at such condition. Applying the unique analytical capability of NanoSIMS to minute samples recovered from LH-DAC opens a new window to probe water and other volatiles in Earth's deep mantle.

Polyphyllin B Suppresses Gastric Tumor Growth by Modulating Iron Metabolism and Inducing Ferroptosis.

Gastric cancer (GC) is one of the most common malignant tumors in the world. GPx4, as the core regulator of ferroptosis, has become a potential molecular target for developing anticancer agents. In the present study, we found that GPx4 was overexpressed and negatively correlated with poor prognosis in GC, while it was associated with the GC development. Molecular docking and structure-based virtual screening assays were used to screen potential GPx4 inhibitors, and we identified a novel GPx4 inhibitor, polyphyllin B (PB), which can induce ferroptosis by down-regulating GPx4 expression in GC cells. It has also been shown to inhibit cell proliferation, suppress invasion and migration, induce apoptosis, and block the cell cycle progression in GC cells in vitro. Then, immunofluorescence and western blotting assay confirmed that PB can regulate the expression of LC3B, TFR1, NOCA4 and FTH1 in vitro, which suggested that suggest that PB may increase the level of Fe2+ by transporting Fe3+ into the cell by TFR1 and promoting NCOA4-dependent iron autophagy. In addition, PB can also suppresses tumor growth in an orthotopic mouse model of GC via regulating the expression of GPx4, TFR1, NOCA4 and FTH1 in vivo. In summary, we confirmed that GPx4 may be a potential target for GC treatment, PB may be a novel and promising drug for the treatment of GC, which shows good antitumor efficacy without causing significant host toxicity via inducing ferroptosis in both gastric cancer cells and mouse models.

A Novel Method for Dynamically Assessing the Prognosis of Patients with pT1 Gastric Cancer: A Large Population-Based Dynamic Prognostic Analysis.

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.

Ruthenium-catalyzed reductive amination of ketones with nitroarenes and nitriles.

The Ru(dppbsa)-catalyzed reductive amination of ketones with nitroarenes and nitriles using H2 as the environmentally benign hydrogen surrogate is developed in this study. Cross-experiments demonstrated that both reactions are initiated by the reduction of nitroarenes or nitriles to the corresponding amines, followed by condensation with ketones to give imines and thereafter hydrogenation. However, the route to the formation of an amino-ligated Ru complex during the reduction of nitroarenes or nitriles, followed by in situ nucleophilic C-N coupling, cannot be completely excluded. This newly developed versatile method features good functional group tolerance, which provides a novel design platform for homogeneous catalysts in constructing motifs of secondary amines.

Prognostic significance of inflammatory and nutritional markers in perioperative period for patients with advanced gastric cancer.

BACKGROUND: It has been reported that inflammatory and nutritional markers are related to prognosis in numerous malignancies. The present study analyzed the significance of these markers' alterations during neoadjuvant chemotherapy in the long-term outcomes in patients with advanced gastric cancer. METHODS: A retrospective review was performed of 437 advanced gastric cancer patients who underwent a neoadjuvant chemotherapy (NACT) regimen followed by surgical treatment. Inflammatory and nutritional markers measured from the blood samples collected from the patients before the first neoadjuvant chemotherapy and after the last neoadjuvant chemotherapy were used for analysis. Statistical analysis, including Mann-Whitney U or chi-square tests, the Kaplan-Meier method and Cox multivariate analysis, were performed to analyze the predictive value of these markers for overall survival outcomes (OS). RESULTS: Most biomarkers, including lymphocyte, leucocyte, neutrophil, monocyte, platelet, LMR, PLR, SII, CRP, CAR, hemoglobulin and albumin levels, changed during NACT (P <  0.05). After separately grouping the patients based on the normal range of hematologic indexes and the change rate (α) of systemic inflammatory and nutritional markers by the cutoff value derived from X-tile (P <  0.05), we found that differentiation, TRG, pre-NACT BMI, pre-NACT platelet counts, post-NACT lymphocyte counts, the change in lymphocyte counts, change in platelet counts and LMR(α), PLR(α), SII(α), and CAR(α) were associated with OS. Multivariate analysis revealed that PLR (α) > - 19% was correlated with a 3.193-fold (95% CI: 2.194-4.649) higher risk of death (P <  0.001) than others. CONCLUSION: NACT could significantly change several inflammatory and nutritional markers in the perioperative period; the platelet counts before NACT, and the change in lymphocytes during NACT truly correlated with long-term outcomes among patients with advanced gastric cancer. The systemic inflammatory marker PLR may be a reliable marker for the prediction of prognosis.

Preoperative chemotherapy combined with para-aortic lymph node dissection has clinical value in the treatment of gastric cancer with para-aortic lymph node metastases.

BACKGROUND: Lymph node metastases often occur in advanced gastric cancer, with some patients presenting with metastases in the para-aortic lymph nodes. There are persistent Controversies about the benefit of para-aortic lymph node dissection (PAND). Our purpose is to probe whether PAND following preoperative chemotherapy had any clinical significance in individuals with PALNs in gastric cancer. MATERIAL AND METHODS: To retrospectively analyze the clinical data of 86 gastric cancer patients (40 in the D2 + PAND group and 46 in the D2 group) who attended the abdominal surgery department of Zhejiang Cancer Hospital between September 1, 2008, and July 30, 2018. RESULTS: In the D2 + PAND group (40 cases), the average number of lymph nodes cleared per case was 4.3 in group 16 (16a2, 16b1), and the postoperative pathology confirmed lymph node positivity in 16 cases, with a metastasis rate of 40%. The median overall survival times were 63 and 34 months for the patients in the D2 + PAND group and D2 group, respectively. The 3-year overall survival (OS) compared to the D2 group (D2 + PAND 69.1% vs. D2 50%, P = 0.012) and a statistically significant difference in 3-year disease-free survival (DFS) (D2 + PAND 69.6% vs. D2 38.3%, P = 0.007). Lymph node dissection extent and recurrence of para-aortic lymph nodes were independent prognostic variables for the patients. The recurrence rate was reduced in the D2 + PAND group compared to the D2 group (D2 + PAND 7.5% vs. D2 26.1%, p = 0.023). CONCLUSIONS: For patients with gastric cancer whose imaging suggests metastasis in the para-aortic lymph nodes, preoperative chemotherapy combined with PAND is an effective and safe treatment that may benefit patient survival.

A literature review on the potential clinical implications of streptococci in gastric cancer.

Streptococcus is widely found in nature and the human body, and most species are not pathogenic. In recent years, studies have found that Streptococcus is associated with gastric cancer. Streptococcus was found to be enriched in the oral cavity, stomach and intestine of gastric cancer patients and found to be increased in gastric cancer tissues, suggesting that Streptococcus may be the pathogenic bacteria underlying gastric cancer. This review discusses the discovery of Streptococcus, the relationship between Streptococcus and gastric cancer, and the possible carcinogenic mechanism of Streptococcus and summarizes the progress of the research on the role of Streptococcus in gastric cancer to provide new ideas for the early detection, diagnosis and treatment of gastric cancer.

High CHAF1A Expression Levels Are Positively-Correlated with PD-L1 Expression and Indicate Poor Prognosis in Gastric Cancer.

Objective: The aim of this study was to analyze the association between the expression of chromatin assembly factor 1 subunit A (CHAF1A) in gastric cancer (GC) and clinicopathological features, disease prognosis, and expression of programmed cell death-ligand 1 (PD-L1). Material and Methods. A total of 140 GC tissue specimens were collected between January 2013 and December 2017. CHAF1A expression in GC and paracancerous tissues was determined. Then, the associations between CHAF1A expression level in the collected tissues and clinicopathological features as well as PD-L1 expression level were investigated. Cox regression analyses were carried out to determine whether CHAF1A is an independent prognostic factor for GC. Finally, the association between CHAF1A expression levels and survival of the GC patients was investigated. Results: A significantly higher level of CHAF1A expression in GC tissues was found compared to that in paracancerous tissues (p=0.042). CHAF1A expression level in GC tissues was found to be strongly associated with family history (p=0.005), smoking history (p=0.016), T stage (p=0.001), tumor marker AFP (p=0.017), tumor marker CEA (p=0.027), and PD-L1 expression (p=0.029). CHAF1A expression was also found to be positively correlated to PD-L1 expression (p=0.012). Moreover, high CHAF1A expression levels were found to lead to poor prognosis (p=0.019). Univariate and multivariate analyses all showed that CHAF1A was an independent poorer prognostic factor for gastric cancer (p=0.021, HR = 1.175, 95% CI: 1.090-2.890 for univariate analyses; p=0.014, HR = 2.191, 95% CI:1.170-4.105 for multivariate analyses). A high level of CHAF1A expression was thus found to be an independent risk factor for GC prognosis. Conclusion: High CHAF1A expression is associated with poor GC prognosis and positively correlated to PD-L1 expression. Thus, CHAF1A expression level may be used as a novel biomarker for GC diagnosis.

Trastuzumab in combination with chemotherapy for HER2-positive metastatic gastric cancer patients underwent conversion therapy.

Background: Conversion surgery is a treatment that aims for R0 resection of primary advanced gastric cancers (GCs) that have responded well to systemic chemotherapy. We investigated the role of conversion therapy in initially unresectable metastatic cancer with positive HER2 status that responded to chemotherapy plus trastuzumab. Methods: A total of 32 metastatic GC patients who underwent systemic chemotherapy plus trastuzumab sequenced by conversion surgery at Zhejiang Cancer Hospital between 2015 and 2020 were retrospectively reviewed. Results: The observed overall survival (OS) and progression-free survival (PFS) for all the patients were 30.2 and 25.1 months, respectively. The 1-year survival rate was 81.25%, and the 1-year PFS rate was 78.13%. Univariate and multivariate analyses demonstrated that liver metastasis (P=0.021), peritoneal metastasis (P=0.047), para-aortic lymph node metastasis (16a1/b2) (P=0.048), macroscopic type 4 (P=0.027), number of noncurative factors (P=0.011), Yoshida et al. category (P=0.021), and inductive chemotherapy cycles (P=0.025) were independent prognostic factors for OS. Conclusions: HER2-positive patients with potentially resectable disease had a remarkably good prognosis after conversion gastrectomy following trastuzumab treatment. Adequate selection of metastatic GC patients for conversion surgery is recommended.

SFRP4 Is a Potential Biomarker for the Prognosis and Immunotherapy for Gastric Cancer.

Purpose: Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family, which functions as either a tumor suppressor or a prooncogenic factor in distinct tumor types. Our research aimed to explore the expression of SFRP4 in gastric cancer, its prognostic significance, and its relationship with immune cell infiltration. Materials and Methods: Gastric cancer and paracancerous tissue specimens from surgically resected gastric cancer patients were collected to construct tissue microarrays, and immunohistochemistry was used to detect the expression of SFRP4, PD-L1, CD3+ T, CD4+ T, and CD8+ T in these microarrays. The differential expression of SFRP4 and its relationship with the immune microenvironment were evaluated using the TIMER and TISIDB databases. Finally, patient survival was assessed. Results: SFRP4 expression was elevated in gastric cancer tissues and linked to a poor prognosis (P=0.021). The 5-year survival rate for patients with high SFRP4 expression was only 39.81% but reached 60.02% for patients with low SFRP4 expression. Increased SFRP4 expression correlated with high CD8+ T-cell infiltration (P=0.015) and positive PD-L1 expression (P=0.036). High SFRP4 expression was an independent predictor of overall survival (P=0.024 in univariable analysis, P=0.011 in multivariable analysis). Using online databases, we found that SFRP4 expression was higher in gastric cancer tissues and substantially was associated with the immune microenvironment. Conclusion: SFRP4 is an oncogenic driver that can predict patient survival time in gastric cancer, as well as an important immune-related factor. SFRP4 may be important for guiding immunotherapy in gastric cancer patients.