Intratumoral microbiota are increasingly recognized for their impact on gastric cancer, with growing evidence highlighting their complexity and significance. This review synthesizes current knowledge on the origins, heterogeneity, detection, and mechanistic roles of intratumoral microbiota in gastric carcinogenesis. In gastric cancer, intratumoral microbiota can originate from mucosal disruption and may migrate from normal adjacent tissues or be influenced by the TME. It exhibits spatial and functional heterogeneity within gastric cancer. Despite challenges in the detection of intratumoral microbiota, advances in deep sequencing and spatial omics have enhanced our understanding of microbial diversity and functionality. Mechanistically, intratumoral microbiota influence gastric cancer development through genetic and epigenetic alterations, signaling pathway modulation, metabolic reprogramming, and regulation of chronic inflammation and immune responses. These insights underscore the microbiota's dual function in both promoting and hindering tumor advancement. Therapeutically, the microbiota's impact on chemotherapy resistance and immune modulation presents opportunities for novel interventions. Integrating microbiome analysis into cancer research and leveraging microbial therapies may enable more effective, personalized treatment strategies. Future research should further elucidate the intricate microbe-tumor interactions to advance clinical applications and improve outcomes for gastric cancer patients.

Helicobacter pylori and Candida spp. are widespread microorganisms found in the human gastrointestinal tract, often coexisting in the same ecological niche. H. pylori, a Gram-negative bacterium, is a well-known pathogen responsible for gastritis, peptic ulcers, and gastric cancer. In contrast, Candida fungi, often detected in food, particularly Candida albicans, are generally considered commensal organisms, but can become opportunistic pathogens under certain conditions. Recent studies suggest a possible link between these microorganisms, highlighting a new survival strategy of H. pylori, that is, its ability to internalize in Candida vacuoles. This phenomenon, confirmed by various microscopic and molecular techniques, may provide H. pylori with protection against adverse environmental conditions, especially clinically important antibiotic therapy. The basic premise of this theory is the ability of H. pylori to penetrate vacuoles in fungal cells, which then become a reservoir of infection, allowing the infection to recur. Understanding the interaction between H. pylori and Candida may offer new insights into the pathogenesis of gastrointestinal diseases and may lead to the development of treatments targeting both organisms simultaneously. The purpose of this article is to review the literature, considering the first observations on this problem in the literature and the current state of knowledge, and to suggest a direction for further research.

Gastric cancer (GC) is one of the most common malignancies worldwide, and Helicobacter pylori (HP) infection is a well-established risk factor for its development. Programmed death-ligand 1 (PD-L1) expression is a crucial biomarker for predicting the efficacy of immune checkpoint inhibitors in cancer treatment. While HP infection and PD-L1 expression in GC may be linked, the relationship between them remains unclear, in part because there have been conflicting results reported from various studies.

To perform a meta-analysis to assess the relationship between HP and PD-L1 expression in patients with GC.

A systematic literature review was conducted using PubMed, Embase, Cochrane Library, and Web of Science databases. Observational studies that examined the association between HP infection and PD-L1 expression in patients with GC were included. Odds ratios and 95% confidence intervals were calculated to estimate the association. Heterogeneity was assessed using Cochrane's Q test and I² statistic. A random-effects model was used due to significant heterogeneity across studies.

Fourteen studies involving a total of 3069 patients with GC were included. The pooled analysis showed a significant association between HP infection and increased PD-L1 expression in GC tissues (odd ratio = 1.69, 95% confidence interval: 1.24-2.29, P < 0.001, I 2 = 59%). Sensitivity analyses confirmed the robustness of these findings. Subgroup analyses did not show significant variation based on geographic region, sample size, or method of PD-L1 assessment. Publication bias was minimal, as shown by funnel plots and Egger's regression test.

HP infection is associated with increased PD-L1 expression in GC, suggesting that HP status may influence the response to programmed cell death protein 1/PD-L1 blockade therapy.

Gastric cancer (GC) remains a prevalent and aggressive malignancy worldwide, characterized by significant morbidity and mortality. The regulator of G-protein signaling 1 (RGS1) plays an oncogenic role in various cancers, including GC, but its clinical relevance and mechanisms remain underexplored. In this pilot study, we investigated RGS1 expression in GC tissues and its potential as a prognostic marker, laying the groundwork for future research. Our analysis of patient data from the TCGA data and our cohort of 375 surgically resected GC patients revealed that RGS1 was upregulated in GC tissues and had prognostic significance (TCGA: adjusted HR:1.49, 95%CI: 1.02-2.18; GC cohort: adjusted HR: 1.38, 95%CI: 1.02-1.85). GO function and KEGG enrichment analyses suggest that RGS1 is involved in macrophage-mediated immune responses in GC. We observed a positive correlation between RGS1 expression and M2 macrophage infiltration. Furthermore, co-occurrence of elevated RGS1 expression and M2 macrophage infiltration predicts a worse prognosis (adjusted HR: 1.73, 95%CI: 1.24-2.42 in our cohort). In vitro, RGS1 upregulation and the presence of M2 macrophages enhanced malignant phenotypes of GC cells. Additionally, we confirmed that RGS1 promoted macrophage recruitment and M2 polarization via upregulation of CCL4 expression in vivo. In conclusion, this study suggests that RGS1 could serve as a promising prognostic marker for GC and a potential target for immunotherapy. However, further investigation with more advanced experimental models is needed to confirm these preliminary findings.

Cholesterol and Helicobacter pylori (H. pylori) are both risk factors for gastric cancer (GC). However, the relationship between cholesterol and H. pylori and their function in the progression of GC are controversial. In this study, we addressed that H. pylori could induce mitochondrial cholesterol accumulation and promote GC proliferation and protect GC cells against apoptosis via cholesterol. Metabolomic and transcriptomic sequencing were used to identify CYP11A1 responsible for H. pylori-induced cholesterol accumulation. In vitro and in vivo function experiments revealed that cholesterol could promote the proliferation of GC and inhibit apoptosis. Mechanically, the interaction of Cytotoxin-associated gene A (CagA) and CYP11A1 redistributed mitochondrial CYP11A1 outside the mitochondria and subsequently caused mitochondrial cholesterol accumulation. The CYP11A1-knockdown upregulated cholesterol accumulation and reproduced the effect of cholesterol on GC in a cholesterol-dependent manner. Moreover, CYP11A1-knockdown or H. pylori infection inhibited mitophagy and maintained the mitochondria homeostasis. H. pylori could contribute to the progression of GC through the CagA/CYP11A1-mitoCHO axis. This study demonstrates that H. pylori can contribute to the progression of GC via cholesterol, and eradicating H. pylori is still prognostically beneficial to GC patients.

Non-antibiotic adjuncts may improve Helicobacter pylori infection control. Our aim was to emphasize curcumin benefits in controlling H. pylori infection. We discussed publications in English mostly published since 2020 using keyword search. Curcumin is the main bioactive substance in turmeric. Curcumin inhibited H. pylori growth, urease activity, three cag genes, and biofilms through dose- and strain-dependent activities. Curcumin also displayed numerous anticancer activities such as apoptosis induction, anti-inflammatory and anti-angiogenic effects, caspase-3 upregulation, Bax protein enhancement, p53 gene activation, and chemosensitization. Supplementing triple regimens, the agent increased H. pylori eradication success in three Iranian studies. Bioavailability was improved by liposomal preparations, lipid conjugates, electrospray-encapsulation, and nano-complexation with proteins. The agent was safe at doses of 0.5->4 g daily, the most common (in 16% of the users) adverse effect being gastrointestinal upset. Notably, curcumin favorably influences the intestinal microbiota and inhibits Clostridioides difficile. Previous reports showed the inhibitory effect of curcumin on H pylori growth. Curcumin may become an additive in the therapy of H. pylori infection, an adjunct for gastric cancer control, and an agent beneficial to the intestinal microbiota. Further examination is necessary to determine its optimal dosage, synergy with antibiotics, supplementation to various eradication regimens, and prophylactic potential.

Various forms of malignancies have been linked to Helicobacter pylori. Despite advancements in chemotherapeutic and surgical approaches, the management of cancer, particularly at advanced stages, increasingly relies on the integration of immunotherapy. As a novel, safe therapeutic modality, immunotherapy harnesses the immune system of the patient to treat cancer, thereby broadening treatment options. However, there is evidence that H. pylori infection may influence the effectiveness of immunotherapy in various types of cancer. This association is related to H. pylori virulence factors and the tumor microenvironment. This review discusses the influence of H. pylori infection on immunotherapy in non-gastrointestinal and gastrointestinal tumors, the mechanisms underlying this relationship, and directions for the development of improved immunotherapy strategies.

Background: COVID-19 has been ravaging the globe for more than three years. Due to systemic immunosuppression of anti-tumor therapy, application of chemotherapy and adverse effects of surgery, the short- and long-term prognosis of cancer patients to COVID-19 are of significant concern. Method: This research included three parts of data. The first part of the data came from the public database that covered Veneto residents. The second part of the data included participants in Guangzhou. The third part of the data was used for MR analysis. We assessed the associations by logistic, linear or Cox regression when appropriate. Result: Lung cancer patients with COVID-19 had shorter progression-free survival (PFS) after COVID-19 (Model II: HR: 3.28, 95% CI: 1.6~6.72; Model III: HR: 3.39, 95% CI: 1.45~7.95), compared with lung cancer patients without COVID-19. Targeted therapy patients recovered from SARS-CoV-2 infection more quickly (Model I: β: -0.58, 95% CI: -0.75~-0.41; Model II: β: -0.59, 95% CI: -0.76~-0.41; Model III: β: -0.57; 95% CI: -0.75~-0.40). Conclusions: PFS in lung cancer patients is shortened by COVID-19. The outcome of COVID-19 in lung cancer patients was not significantly different from that of the healthy population. In lung cancer patients, targeted therapy patients had a better outcome of COVID-19, while chemotherapy patients had the worst.

Carcinogenic viruses (oncoviruses) can initiate cancer, but their impact on established cancer varies. Some of these viruses prolong survival while others shorten it. This study classifies oncoviruses into two categories: viruses which induce a strong CD8+T cell reaction in non-cancerous tissues, and viruses which induce a weak CD8+ T cell reaction in non-cancerous tissues. The classification proves useful in predicting the effect of oncoviruses on the prognosis of solid cancers. Therefore, while eliminating carcinogenic viruses in healthy individuals (for example by immunization) may be important for cancer prevention, this study suggests that only viruses which induce a weak CD8+ T cell reaction should be eradicated in established solid tumors. The model correctly predicts the effect of oncoviruses on survival for six out of seven known oncoviruses, indicating that immune modulation by oncoviruses has a prominent effect on prognosis. It seems that CD8+ T cell response to oncoviruses observed in infected benign tissues is retained in infected tumors. Clinical significance: the effect of oncoviruses on solid cancer prognosis can be predicted with confidence based on immunological responses when clinical data are unavailable.

Helicobacter pylori is a gastrointestinal pathogen that infects around half of the world's population. H. pylori infection is the most severe known risk factor for gastric cancer (GC), which is the second highest cause of cancer-related deaths globally. We conducted a systematic review and meta-analysis to assess the global prevalence of GC in H. pylori-infected individuals.

We performed a systematic search of the PubMed, Web of Science, and Embase databases for studies of the prevalence of GC in H. pylori-infected individuals published from 1 January 2011 to 20 April 2021. Metaprop package were used to calculate the pooled prevalence with 95% confidence interval. Random-effects model was applied to estimate the pooled prevalence. We also quantified it with the I2 index. Based on the Higgins classification approach, I2 values above 0.7 were determined as high heterogeneity.

Among 17,438 reports screened, we assessed 1053 full-text articles for eligibility; 149 were included in the final analysis, comprising data from 32 countries. The highest and lowest prevalence was observed in America (pooled prevalence: 18.06%; 95% CI: 16.48 - 19.63; I2: 98.84%) and Africa (pooled prevalence: 9.52%; 95% CI: 5.92 - 13.12; I2: 88.39%). Among individual countries, Japan had the highest pooled prevalence of GC in H. pylori positive patients (Prevalence: 90.90%:95% CI: 83.61-95.14), whereas Sweden had the lowest prevalence (Prevalence: 0.07%; 95% CI: 0.06-0.09). The highest and lowest prevalence was observed in prospective case series (pooled prevalence: 23.13%; 95% CI: 20.41 - 25.85; I2: 97.70%) and retrospective cohort (pooled prevalence: 1.17%; 95% CI: 0.55 - 1.78; I 2: 0.10%).

H. pylori infection in GC patients varied between regions in this systematic review and meta-analysis. We observed that large amounts of GCs in developed countries are associated with H. pylori. Using these data, regional initiatives can be taken to prevent and eradicate H. pylori worldwide, thus reducing its complications.

Gastric cancer (GC) is a prevalent malignant tumor worldwide and ranks as the fourth leading cause of cancer-related mortality. Upper gastrointestinal bleeding (UGIB) is a frequent complication of GC. Radical gastrectomy and palliative therapy are widely used surgical procedures in the clinical management of GC. This study intends to probe the clinical efficacy and safety of radical gastrectomy and palliative therapy on the basis of exploratory laparotomy in patients with GC combined with UGIB, hoping to provide valuable information to aid patients in selecting the appropriate surgical intervention.

To investigate the clinical efficacy and safety of exploratory laparotomy + radical gastrectomy and palliative therapy in patients with GC and UGIB combined.

A total of 89 GC patients admitted to the First Affiliated Hospital of the University of South China between July 2018 and July 2020 were selected as participants for this study. The 89 patients were divided into two groups: radical resection group (n = 46) treated with exploratory laparotomy + radical gastrectomy and Palliative group (n = 43) treated with palliative therapy. The study compared several variables between the two groups, including surgical duration, intraoperative blood transfusion volume, postoperative anal exhaust time, off-bed activity time, length of hospitalization, and incidence of complications such as duodenal stump rupture, anastomotic obstruction, and postoperative incision. Additionally, postoperative immune function indicators (including CD3+, CD4+, CD8+, CD4+/CD8+, and CD3+/HLADR+), immunoglobulin (IgG and IgM), tumor markers (CEA, CA199, and CA125), and inflammatory factors (IL-6, IL-17, and TNF-α) were assessed. The surgical efficacy and postoperative quality of life recovery were also evaluated. The patients were monitored for survival and tumor recurrence at 6 mo, 1 year, and 2 years post-surgery.

The results indicated that the duration of operation time and postoperative hospitalization did not differ between the two surgical procedures. However, patients in the radical resection group exhibited shorter intraoperative blood loss, anus exhaust time, off-bed activity time, and inpatient activity time than those in the Palliative group. Although there was no substantial difference in the occurrence of postoperative complications, such as duodenal stump rupture and anastomotic obstruction, between the radical resection group and Palliative group (P > 0.05), the radical resection group exhibited higher postoperative immune function indicators (including CD3+, CD4+, CD8+, etc.) and immunoglobulin levels (IgG, IgM) than the Palliative group, while tumor markers and inflammatory factors levels were lower than those in the radical resection group. Additionally, surgical efficacy, postoperative quality of life, and postoperative survival rates were higher in patients who underwent radical gastrectomy than in those who underwent palliative therapy. Moreover, the probability of postoperative tumor recurrence was lower in the radical gastrectomy group compared to the palliative therapy group, and these differences were all statistically significant (P < 0.05).

Compared to palliative therapy, exploratory laparotomy + radical gastrectomy can improve immune function, reduce the levels of tumor markers and inflammatory factors, improve surgical efficacy, promote postoperative quality of life recovery, enhance survival rates, and attenuate the probability of tumor recurrence.

Gastrointestinal (GI) cancers account for 35% of cancer-related deaths, predominantly due to their ability to spread and generate drug-tolerant metastases. Arising from different locations in the GI system, the majority of metastatic GI malignancies colonise the liver and the lungs. In this context, circulating tumour cells (CTCs) are playing a critical role in the formation of new metastases, and their presence in the blood of patients has been correlated with a poor outcome. In addition to their prognostic utility, prospective targeting of CTCs may represent a novel, yet ambitious strategy in the fight against metastasis. A better understanding of CTC biology, mechanistic underpinnings and weaknesses may facilitate the development of previously underappreciated anti-metastasis approaches. Here, along with related clinical studies, we outline a selection of the literature describing biological features of CTCs with an impact on their metastasis forming ability in different GI cancers.

Gastric cancer (GC) is one of the most common malignant tumors with a high incidence and mortality. Microbiota play a significant role in human health and disease. We aimed to investigate the prognostic value of the gastric microbiota in different stomach microhabitats. We used our previously published 16S rRNA gene sequence data. We retrospectively enrolled a cohort of 132 patients with GC with complete prognostic information and selected 78 normal tissues, 49 peritumoral tissues, and 112 tumoral tissues for microbiota analysis. Patients with different prognoses showed different gastric microbiota compositions and diversity. The association network of the abundant gastric microbiota was more complicated in patients with poor prognoses. In the peritumoral microhabitat of patients with good prognoses, Helicobacter was significantly increased, whereas Halomonas and Shewanella were significantly decreased relative to that in the peritumoral microhabitat of patients with poor prognoses. PiCRUSt analysis revealed that the peritumoral microbiota had more different Kyoto Encyclopedia of Genes and Genomes pathways than did the tumoral and normal microbiota. This study evaluated the long-term prognostic value of the gastric mucosal microbiota in patients with GC. These findings suggested that the characteristic alterations of the gastric mucosal microbiota may be markers for clinical outcomes in these patients.

High expression of programmed death ligand-1 (PD-L1) has been related to good response to immunotherapy patients with gastric cancer (GC). However, the influence of Helicobacter pylori (HP) infection on PD-L1 expression in GC remains unknown. A meta-analysis was performed to evaluate the association between HP infection and PD-L1 expression in GC.

Observational studies that investigated the relationship between HP infection and PD-L1 expression in patients with GC were obtained by search electronic databases, including PubMed, Embase, Cochrane's Library and Web of Science. A random-effect model incorporating the possible influence of between-study heterogeneity was used to pool the results.

Ten studies with 1870 patients with GC contributed to the meta-analysis. Pooled results showed that HP infection was significantly associated with the tumour expression of PD-L1 (odds ratio [OR]: 1.90, 95% confidence interval: 1.33-2.72, p < .001; I²  = 53%). Subgroup analyses showed that the association between HP infection and PD-L1 expression in GC was not significantly affected by sample size, methods for PD-L1 evaluation and quality score (p for subgroup analyses all >.05). However, a stronger association was observed in studies with higher prevalence of HP infection (≥35%, OR: 2.58) as compared with those with lower prevalence (<35%, OR: 1.45, p for subgroup difference = .04).

Helicobacter pylori infection in GC patients is associated with tumour expression of PD-L1, suggesting HP infection may be a predictor of good response to immunotherapy in GC.

Gastric cancer (GC) remains the fifth most common malignant tumor and the third leading cause of cancer death, despite the decline in incidence and mortality worldwide over the past five decades. Currently, the roles of Helicobacter pylori (H. pylori) in the development of GC have been established. The effects of H. pylori are mediated through interactions of H. pylori pathogen-associated molecular patterns (PAMPs) with pattern-recognition receptors (PRRs) located on immune and epithelial cells. It is known that this interaction leads to the generation of reactive oxygen species (ROS), activation of the mechanisms of angiogenesis, epithelial-mesenchymal transformation (EMT), and immunological tolerance. Not all this excludes the possibility that H. pylori may have an effect not only on the induction, but also on the mechanisms of GC progression. In this review, we will consider the main structural elements of the innate immune system and the mechanisms of their interaction with H. pylori; the possible role of H. pylori in GC progression; relationship of H. pylori with clinical and pathological characteristics and prognosis of GC, as well as data on the effect of eradication therapy on long-term results of GC patient treatment.

Helicobacter pylori is closely associated with gastric cancer. During persistent infection, Helicobacter pylori can form a microenvironment in gastric mucosa which facilitates the survival and colony formation of Helicobacter pylori. Tumor stromal cells are involved in this process, including tumor-associated macrophages, mesenchymal stem cells, cancer-associated fibroblasts, and myeloid-derived suppressor cells, and so on. The immune checkpoints are also regulated by Helicobacter pylori infection. Helicobacter pylori virulence factors can also act as immunogens or adjuvants to elicit or enhance immune responses, indicating their potential applications in vaccine development and tumor immunotherapy. This review highlights the effects of Helicobacter pylori on the immune microenvironment and its potential roles in tumor immunotherapy responses.