Development Of Adenocarcinoma Research Articles

Oxidative stress-associated gene signature predicts the prognosis and therapy response in prostate adenocarcinoma

Background: Oxidative stress contributes to the development of prostate adenocarcinoma (PRAD). However, the prognosis prediction and therapy response predicted based on oxidative stress-associated genes lacked comprehensive study. Herein, an integrated bioinformatics approach was adopted to identify the prognosis-associated oxidative stress genes for PRAD. Methods: From Gene-Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, the transcriptomic data and clinical data were collected. Genes related to oxidative stress were retrieved from oxidative stress pathway "GOBP_RESPONSE_TO_OXIDATIVE_STRESS" in the MsigDB. A risk model was constructed based on the hub genes selected by both WGCNA analysis and LASSO analysis. GEO cohort was used for verifying the model robustness. By running CIBERSORT and ESTIMATE algorithm, immune cell infiltration was quantified. TIDE algorithm and Spearman correlation analysis were used for evaluating the immunotherapy response and drug sensitivity. RT-qPCR analysis and CCK-8 were carried out to validate the results. Results: We established oxidative stress-related gene signature (NUDT7, NTRK3, MAP3K12, DRD5, C3orf18, and B3GALT2) as an independent factor for the prognostic survival of PRAD. In virto experiments showed that MAP3K12 had a higher expression in PRAD cell lines, and knockdown of MAP3K12 inhibited PC3 cell viability. The risk score was positively linked with T_ cells_ regulatory_ Tregs and Macrophages_ M2 and negatively linked with Plasma_cells. High-risk patients showed higher expressions of PDCD1, CD274, CTLA4, LAG3, PDCDILG2, BTLA, HAVCR2, TIGIT, and higher myeloid-derived suppressor (MDSC) score. Docetaxel, Cisplatin, and Bicalutamide could benefit low-risk patients more. Calibration curves and DCA showed an accurate prediction by the nomogram. Conclusion: We established a novel and reliable prognostic model for PRAD patients.

P53-loss induced prostatic epithelial cell plasticity and invasion is driven by a crosstalk with the tumor microenvironment

Prostate cancer is a heterogeneous disease with a slow progression and a highly variable clinical outcome. The tumor suppressor genes PTEN and TP53 are frequently mutated in prostate cancer and are predictive of early metastatic dissemination and unfavorable patient outcomes. The progression of solid tumors to metastasis is often associated with increased cell plasticity, but the complex events underlying TP53-loss-induced disease aggressiveness remain incompletely understood. Using genetically engineered mice, we show that Trp53 deficiency in Pten-null prostatic epithelial cells (PECs) does not impact early cell proliferation and neoplasia formation, nor growth arrest and senescence entry at a later time. However, Trp53-deficiency enhances invasive adenocarcinoma development and promotes metastatic cell dissemination. Importantly, our single-cell transcriptomic and chromatin accessibility analyses combined with histological examinations uncovered an epithelial cell population characterized by an induction of Jak/Stat3 signaling and displaying mesenchymal features. Moreover, we show that the transcriptomic signature of this cell population is prominent in tumors of patients with high-risk prostate cancer or metastatic disease. In addition, our in vivo and organoid-based experiments provide evidence that PEC plasticity occurs through bi-directional communication with cancer-associated fibroblasts (CAFs). Thus, our study demonstrates that p53 loss induces a protumorigenic crosstalk between PECs and CAFs, and identifies new vulnerabilities that might be targeted to limit cancer progression.

Identification of KRT16 and ANXA10 as cell cycle regulation genes for lung adenocarcinoma based on self-transcriptome sequencing of surgical samples and TCGA public data mining

AimThis study aimed to identify the genes associated with the development of lung adenocarcinoma (LUAD) and potential therapeutic targets.MethodsDifferentially expressed genes (DEGs) were identified by self-transcriptome sequencing of tumor tissues and paracancerous tissues resected during surgery and combined with The Cancer Genome Atlas (TCGA) data to screen for the genes associated with LUAD prognosis. The expression was validated at mRNA and protein levels, and the gene knockdown was used to examine the impact and underlying mechanisms on lung cancer cells.ResultsA total of 227 DEGs were identified by transcriptome sequencing, and the 20 DEGs with the most significant differences were used for co-analysis with TCGA data. The findings suggested that KRT16 and ANXA10 might have an important role in the development of LUAD after validating the mRNA and protein expression levels at the cellular level. The knockdown of KRT16 and ANXA10 inhibited the proliferation of lung cancer cells, and the cell cycle was blocked in the G1 phase. The expression of the G1/S–phase cell cycle checkpoint–related proteins cyclin D1 and cyclin E was inhibited by KRT16 and ANXA10 knockdown, respectively. The tumor formation ability decreased after KRT16 or ANXA10 knockdown in vivo.ConclusionsKRT16 and ANXA10 are potential genes regulating the development of LUAD. Also, they may be potential targets for the targeted therapy of LUAD by inhibiting the proliferation of lung cancer cells and blocking the cell cycle by affecting key protein expression levels at cell cycle checkpoints.

Identification of Metabolic Characteristic–Pancreatic Ductal Adenocarcinoma Associations Using Mendelian Randomization and Metabolomics

BackgroundMetabolic reprogramming is increasingly recognized as a crucial factor influencing the development, progression, and prognosis of pancreatic ductal adenocarcinoma (PDAC). Despite this, the potential association of specific metabolic characteristics and PDAC remains ambiguous due to the variability introduced by individual patient differences. In this study, we aimed to find out metabolic pathways that may be associated with the overall survival (OS) of PDAC patients.MethodsWe utilized Mendelian randomization (MR) to assess the associations between 1400 metabolites and metabolite ratios and PDAC. We performed functional annotation and pathway enrichment analysis on both significant metabolites and the shared proteins corresponding to the significant metabolite ratios. Additionally, we analyzed peripheral blood metabolites from 32 PDAC patients to correlate metabolites with clinicopathological features and OS. Functional enrichment analysis was also conducted on the significant metabolites.ResultsOur MR analysis revealed 55 metabolites/metabolite ratios associated with PDAC. Among the top 20 enriched metabolic pathways involving proteins related to significant metabolite ratios, seven were associated with amino acid metabolism, three with carbohydrate metabolism, and two with lipid metabolism. Serum metabolomics of PDAC patients highlighted significant upregulation in pathways related to primary bile acid biosynthesis, as well as taurine and hypotaurine metabolism, which correlated negatively with OS. Conversely, pathways involved in arginine biosynthesis, arginine and proline metabolism, and aminoacyl-tRNA biosynthesis were notably downregulated and positively associated with OS. Both upregulated and downregulated differential metabolites were notably enriched in the pyrimidine metabolism pathway, which was linked to poorer OS. These associations were corroborated by MR analysis.ConclusionThe study provides valuable insights into the metabolic characteristics associated with PDAC, offering a reference point for improving diagnosis and treatment for PDAC.

Overexpression of IL-6 and STAT3 may provide new insights into ovine pulmonary adenocarcinoma development

BackgroundOvine pulmonary adenocarcinoma (OPA) is caused by Jaagsiekte sheep retrovirus (JSRV) and is considered an important potential animal model for human lung cancer. The precise mechanisms of OPA oncogenesis are still uncertain. The transcription factor signal transducer and activator of transcription 3 (STAT3) is activated by interleukin-6 (IL-6) in many cancers, but this aspect is unknown in OPA. We therefore aimed to evaluate the expression of IL-6 and STAT3 in OPA for its potential role in pulmonary carcinogenesis.ResultsLung tissues from 9 grossly normal and JRSV-negative sheep and 20 cases of JSRV-positive OPA sheep were included in the study. Tissue samples were stained with antibodies against IL-6, STAT3, and JSRV-MA. IL-6 and STAT3 were further quantified in both groups using Western Blot (WB). Immunohistochemically, IL‑6 was expressed in stromal, inflammatory, and epithelial cells in all cases of OPA, while STAT3 immunoexpression was restricted to epithelial cells. In the OPA group, the percentage of immunolabelled cells for STAT3 accounted for a mean value of 96%. Using the H-SCORE method, 95% of cases were considered positive for STAT3 expression. Control tissues showed multifocal and weak immunoexpression for both markers. Using WB analyses, a highly significant amount of both IL-6 (p = 0.0078) and STAT3 (p < 0.0001) proteins were present in lung neoplasms, by comparison to the control lungs.ConclusionsOur data showed overexpression of IL-6 and STAT3 in lung tissues from OPA compared to lungs from JSRV-negative sheep. These results suggest a potential role of IL6-STAT3 in OPA carcinogenesis.

Integrated analysis of single-cell and bulk-RNA sequencing for the cellular senescence in prognosis of lung adenocarcinoma

Non-small cell lung cancer (NSCLC), half of which are lung adenocarcinoma (LUAD), is one of the most widely spread cancers in the world. Telomerase, which maintains telomere length and chromosomal integrity, enables cancer cells to avoid replicative senescence. When telomerase is inhibited, cancer cells’ senescence began, preventing them from growing indefinitely. Cellular senescence and telomeres are intrinsically linked. As of yet, still laking a systematic study of the involvement of telomere-senescence related genes in lung adenocarcinoma development. In this study, myeloid cells were identified as the cell type which are most correlated with cellular senescence based on its highest telomere-related gene activity. GO, KEGG, GSEA and GSVA analyses were used to explore the biological function of telomere-senescence related genes in LUAD. The combined analysis of single-cell RNA-sequencing and bulk-RNA sequencing identified a gene signature composed of 14 genes which can accurately predict the prognosis of patients with LUAD. In one training and four validation sets, patients with higher Telomere Related Gene Signature (TRGS) had a worse prognosis than those with lower TRGS. Different TRGS patient groups showed varying degrees of immune cell infiltration, frequency of gene missense mutation, sensitivity to different drugs, and tumor mutation burden (TMB). Collectively, we developed a brand new signature composed of telomere-senescence related genes that can accurately predicts patients’ prognosis in LUAD, which provides new insights for future research into the role of cellular senescence in LUAD.

A novel interplay between bacteria and metabolites in different early-stage lung cancer: an integrated microbiome and metabolome analysis.

The carcinogenesis mechanism of early-stage lung cancer (ESLC) remains unclear. Microbial dysbiosis is closely related to tumor development. This study aimed to analyze the relationship between microbiota dysbiosis in ESLC. We investigated a total of 108 surgical specimens of lung nodules, including ground glass nodules (GGN) diagnosed as lung adenocarcinoma (n = 25), solid nodules (SN) diagnosed as lung adenocarcinoma (n = 27), lung squamous carcinoma (LUSC) presenting as solid nodules (n = 26), and benign pulmonary nodules (BPD) (n = 30) that were collected. 16S rDNA amplicon sequencing and non-targeted metabolomics analysis were performed in all of the specimens. We found a significantly lower microbiota richness in SN than in the GGN and LUSC. Ralstonia may be an important flora promoting the development of early lung adenocarcinoma, while Feacalibacterium and Blautia play a protective role in the progression of GGN to SN. Akkermansia, Escherichia-shigella, and Klebsiella exhibited high abundance in early lung squamous carcinoma. Compared with BPD, the differential metabolites of both early adenocarcinomas (SN and GGN) are mainly involved in energy metabolic pathways, while early LUSC is mainly involved in glutathione metabolism, producing and maintaining high levels of intracellular redox homeostasis. A correlation analysis revealed that different microbiota in GGN may function in energy metabolism via N-acetyl-1-aspartylglutamic acid (NAAG) when compared to BPD, while creatine and N-acetylmethionine were the main relevant molecules for the function of differential microbiota in LUSC. Our study identified that early-stage lung adenocarcinoma and squamous carcinoma differ in microbial composition and metabolic status. Ralstonia may be an important flora promoting the development of early lung adenocarcinoma, while Feacalibacterium and Blautia play a protective role in the progression of GGN to SN. Conversely, Akkermansia, Escherichia-shigella, and Klebsiella exhibited high abundance in early lung squamous carcinoma. The metabolites of both early adenocarcinomas (SN and GGN) are mainly involved in energy metabolic pathways, while early LUSC is mainly involved in glutathione metabolism. Our study provides new insights into the carcinogenesis of ESLC.

Pancreatic cancer-derived extracellular vesicles remodel the tumor microenvironment and enhance chemoresistance by delivering KRASG12D protein to cancer-associated fibroblasts.

KRAS mutations are instrumental in the development and progression of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the efficacy of direct targeting of KRAS mutations to inhibit tumor development remains doubtful. It is therefore necessary to gain a deeper insight into the mechanism in which KRAS mutations influence the effectiveness of clinical treatments. In this study, KRASG12D protein was detected in cancer-associated fibroblasts (CAFs) from clinical samples of pancreatic ductal adenocarcinoma (PDAC). In vitro experiments demonstrated that KRASG12D protein in CAFs was not expressed from its own mutant gene but was derived from the ingestion of tumor cell-derived extracellular vesicles (EVs). The presence of KRASG12D protein in CAFs resulted in enhanced proliferation and migration. Furthermore, KRASG12D-containing CAFs were observed to promote tumor chemoresistance to gemcitabine treatment both in vitro and in vivo. Application of a KRAS mutation-specific inhibitor, MRTX1133, has been demonstrated to reverse chemoresistance in PDAC. Moreover, clinical data suggest that patients with KRAS mutations have poorer prognosis following adjuvant chemotherapy. These findings elucidate the mechanism by which oncogenic KRAS mutations promote cancer chemoresistance and remodel tumor environment in a non-autonomous manner, suggesting a novel strategy for targeting KRAS mutations to enhance chemosensitivity in PDAC.

Liver transplantation in glycogen storage disease type III: A case-series.

Glycogen storage disease type III (GSD III) is a rare metabolic disorder characterized by a deficiency of liver and muscle amylo-1,6-glucosidase. This condition presents with severe hepatic symptoms in childhood, mostly hepatomegaly, hypoglycemia in half of patients, while muscular complications may predominate in adulthood. Hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC) are common complications in older patients. Therefore, regular monitoring, including HCC screening, is essential for effective disease management. In some severe cases, liver transplantation (LT) may be necessary to treat life-threatening complications. Here, we report the cases of three adult patients who required LT during the course of GSD III. Case #1: Diagnosis of GSD III was made in childhood, with development of hepatocellular carcinoma requiring partial hepatectomy followed by LT due to post-operative complications. The patient recovered well and had favorable surveillance over a seven-year period. Case #2: Diagnosis of GSD III in early childhood, with progression to cirrhosis in adulthood. Severe hepatic encephalopathy necessitated urgent transplantation, with a favorable recovery, although muscular symptoms remained present. Case #3: Diagnosis of GSD III in childhood, followed by later development of hepatocellular adenocarcinoma requiring LT. The patient recovered well and did not exhibit post-transplant muscular symptoms. Post-LT outcome was positive for all three GSD III patients, with significant improvement in liver function and no complications related to immunosuppression. Long-term hepatic monitoring is essential for early detection of complications such as cirrhosis and HCC. LT indications should be individually evaluated, preferring less invasive options. These cases highlight the importance of a multidisciplinary approach to the effective management of GSD III, with particular attention to hepatic and muscular surveillance.

The role of KRT18 in lung adenocarcinoma development: integrative bioinformatics and experimental validation

Lung adenocarcinoma (LUAD) represents one of the most common subtypes of lung cancer with high rates of incidence and mortality, which contributes to substantial health and economic demand across the globe. Treatment today mainly consists of surgery, radiotherapy, and chemotherapy, but their efficacy in advanced stages is often suboptimal and emphasizes the clear need for new biomarkers and therapeutic targets. Using comprehensive bioinformatics analyses consisting of the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), immune infiltration analysis and functional enrichment analysis, and single-cell analysis, we examined the potential of keratin 18 (KRT18) as a candidate biomarker in advanced LUAD. KRT18 was significantly elevated in LUAD tissue relative to normal adjacent tissue (p < 0.05), and its expression was correlated with poor clinical-pathological features and inferior prognostic outcome. Furthermore, KRT18 expression was associated with several populations of immune cells, suggesting KRT18 may contribute to the local tumor microenvironment and potentially pathways of immune evasion. Survival analysis indicated that elevated KRT18 expression correlated with poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI), reinforcing its legitimacy as a prognostic tool (AUC = 0.846). Importantly, gene enrichment analysis found KRT18-associated genes enriched for pathways associated with lymphocyte differentiation and immune response pathways, which provides mechanistic insight into biological effects attributed to KRT18. Notably, NU.1025 has demonstrated the capability of reversing KRT18-modulated oncogenic features, and targeted therapeutic strategies can be developed moving forward. In conclusion, our data demonstrate that KRT18 has utility as a potential biomarker but may also serve as a therapeutic target in LUAD and merit further investigation into underlying mechanistic functions and potential therapeutic roles in the clinic.

The regulation of the cell cycle and epithelial-mesenchymal transition through FUCA2/GGH signaling promotes the progression of lung adenocarcinoma.

The development of lung adenocarcinoma (LUAD) is intricately linked with cell cycle regulation and epithelial-mesenchymal transition (EMT). Our study, leveraging bioinformatics and database analysis, identified FUCA2 as a key gene influencing the prognosis and progression of LUAD. We observed that FUCA2 is highly expressed in LUAD and correlates with poor outcomes. Functionally, we assessed the role of this gene through cell cloning, scratch assays, transwell migration, and western blotting, revealing that FUCA2 knockdown significantly inhibits tumor cell proliferation and migration, downregulates the expression of cell cycle and EMT-related proteins, and markedly reduces tumor burden. Mechanistically, pathway enrichment analysis identified GGH as a downstream target of FUCA2. Knockdown of GGH similarly inhibits the proliferation, migration, and cell cycle progression of LUAD cells. FUCA2 upregulates GGH to modulate cell cycle and EMT in LUAD. Collectively, our findings indicate that the FUCA2/GGH axis promotes LUAD progression by regulating cell cycle and EMT.

Bioinformatics analysis of colorectal cancer transcriptomic data reveals novel prognostic signature and potential biomarker genes

Objective Colorectal cancer (CRC) is a type of digestive system cancer. At the molecular level, some factors, including genetic and epigenetic factors, as well as various signaling pathways such as oxidative stress and inflammation, play an active role in the onset of CRC. Genetic and epigenetic mutations, particularly in oncogenes and tumor suppressor genes, occur during colorectal adenocarcinoma development as a result of a change in gastrointestinal epithelial cell proliferation and self-renewal rates. This study aimed to determine the genes and molecular mechanisms that play a role in the emergence of this disease by analyzing the CRC data. Material and methods Microarray data selected for bioinformatics analysis is Gene Expression data stored with the code GSE110224 in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Gene expression analysis, functional clustering analysis, enrichment analysis, and pathway analysis were performed using this data set. Results Analysis of raw transcriptomic data revealed 1770 common DEGs in CRC. While the expression level of 769 of these genes increased, the expression level of 1001 genes decreased. A Protein–protein interaction (PPI) network was created from the first 25 genes with increased expression levels and 11 signature genes were identified. Increased expression of REG1A, MMP3, FOXQ1 and CEMIP genes and decreased expression of AQP8, CA1, CLDN8, PYY, CA4, CEACAM7 and SLC30A10 genes were observed. Conclusions This approach revealed a CRC-specific molecular profile and may provide some guidance for further investigation of potential biomarkers for diagnosis and prognosis prediction of CRC patients.

Spatially resolved gene expression profiling of tumor microenvironment reveals key steps of lung adenocarcinoma development

The interaction of tumor cells and their microenvironment is thought to be a key factor in tumor development. We present spatial RNA profiles obtained from 30 lung adenocarcinoma patients at the non-invasive and later invasive stages. We use spatial transcriptome sequencing data in conjunction with in situ RNA profiling to conduct higher resolution analyses. The detailed examination of each case, as well as the subsequent computational analyses based on the observed diverse profiles, reveals that significant changes in the phenotypic appearances of tumor cells are frequently associated with changes in immune cell features. The phenomenon coincides with the induction of a series of cellular expression programs that enable tumor cells to transform and break through the immune cell barrier, allowing them to progress further. The study shows how lung tumors develop through interaction in their microenvironments.

Fatty Acid Metabolism Signature Contributes to the Molecular Diagnosis of a Malignant Gastric Cancer Subtype with Poor Prognosis and Lower Mutation Burden.

Gastric cancer (GC) is a common gastrointestinal tumor with high morbidity and mortality. Fatty acid metabolism (FAM) contributes to GC development. Patents have been issued for the use of compositions comprising fatty acid analogues for the treatment of many clinical conditions. However, its clinical significance and its relationship with tumor-related mutations have not been thoroughly discovered. This study was conducted to analyze and explore FAM-related genes' molecular characteristics, prognostic significance, and association with tumor- related mutations. The gastric adenocarcinoma's transcriptome, clinical data, and tumor mutation load (TMB) data were downloaded from TCGA and GEO databases. The differentially expressed FAM genes (FAM DEGs) between cancer and control samples were screened, and their correlation with TMB and survival was analyzed. A PPI network of FAM DEGs was constructed, and a downscaling clustering analysis was performed based on the expression of the FAM DEGs. Further immuno- infiltration and GO/KEGG enrichment analyses of the identified FAM clusters were performed to explore their heterogeneity in biological functions. The effects of FAM score and gastric cancer (STAD) on TMB, MSI, survival prognosis, and drug sensitivity were jointly analyzed, and finally, a single-gene analysis of the obtained core targets was performed. Through differential analysis, 68 FAM DEGs were obtained, and they were highly associated with STAD tumor mutation load. In addition, a high FAM DEGs CNV rate was observed. The PPI network showed a complex mutual correlation between the FAM DEGs. Consensus clustering classified the patients into three clusters based on the FAM DEGs, and the clusters presented different survival rates. The GSVA and immune infiltration analysis revealed that metabolism, apoptosis, and immune infiltration-related pathways were variated. In addition, FAM genes, STAD prognostic risk genes, and PCA scores were closely associated with the survival status of STAD patients. FAM score was closely correlated with STAD TMB, MSI, and immunotherapy, and the TMB values in the low FAM score group were significantly higher than those in the high FAM score group. Finally, combining the above results, it was found that the core gene PTGS1 performed best in predicting STAD survival prognosis and TMB/MSI/immunotherapy. Fatty acid metabolism genes affect the development of gastric adenocarcinoma and can predict the survival prognosis, tumor mutational load characteristics, and drug therapy sensitivity of STAD patients, which can help explore more effective immunotherapy targets for GC.

In Vitro and Vivo Experiments Revealing Astragalin Inhibited Lung Adenocarcinoma Development via LINC00582/miR‐140‐3P/PDPK1

ABSTRACTThis study aimed to explore the mechanism of the development of lung adenocarcinoma (LUAD) treated by astragalin. Transcriptome sequencing was performed to obtain the gene profile of LUAD treated by astragalin. Combining with bioinformatics analysis including differential gene screening, function enrichment analysis (gene ontology and KEGG), and ceRNA construction, we obtained the novel mechanism of lncRNA mediated miRNA/mRNA axis. Then, the cell experiments were performed to examine the role of lncRNA in cell proliferation, migration and invasion, and apoptosis for LUAD treated with astragalin. Moreover, the tumor formation in nude mice was carried out to detect the ceRNA mechanism in LUAD treated by astragalin in vivo. The lncRNA mediated ceRNA network was obtained, that is, LINC00852 LINC00582/miR‐140‐3p/PDPK1 played an important role in LUAD treated by astragalin. Function experiments indicated that si‐LINC00852 inhibited LUAD cell proliferation, migration and invasion, and promoted cell apoptosis via miR‐140‐3p/PDPK1 (p &lt; 0.05, p &lt; 0.01). The animal experiments further confirmed that si‐LINC00852 inhibited tumor growth through miR‐140‐3p/PDPK1 in vivo. Conversely, this study provides comprehensive insights into the diagnostic and therapeutic implications of LINC00582 in LUAD, LINC00582 mediated miR‐140‐3p/PDPK1 axis was the novel drug target of astragalin for treating LUAD.

OS EFEITOS DA TERAPIA DE ERRADICAÇÃO DO HELICOBACTER PYLORI SOBRE A INCIDÊNCIA DO ADENOCARCINOMA GÁSTRICO

INTRODUCTION: Helicobacter pylori is the major risk factor for the development of gastric adenocarcinoma, and may increase its risk by two times. Thus, in the last twenty years, many studies have investigated whether eradicating this agent reduces the risk of gastric cancer. However, the results were initially inconsistent. Therefore, this systematic review was carried out to identify the impact of H. pylori eradication on the incidence of gastric adenocarcinoma. METHOD: Using the Pubmed, Cochrane, Medline, and LILACS databases, a systematic review of studies involving H. pylori eradication treatment and the incidence of gastric adenocarcinoma was carried out from 2019 to 2024. Meta-analyses, reviews, systematic reviews, clinical trials, and randomized controlled trials in English, involving humans, were included in the review. RESULTS: 12 studies were included. All of them showed that the eradication of H. pylori reduced the incidence of gastric adenocarcinoma in individuals without preneoplastic lesions, so that this decrease ranged from 43% to 76% among the articles (CI=95%). DISCUSSION: Gastric adenocarcinoma is unlikely to develop in those not infected with H. pylori. Thus, investigating the effects of the eradication of this bacterium is of great interest to public health. Many factors interfere with the relationship between H. pylori and host and, therefore, with the development of gastric cancer. To mention, the socioeconomic condition and specific virulence factors. Another challenge in the issue of H. pylori is the treatment of the infection, due to the variety of strains and antimicrobial resistance, making it difficult to eradicate. In countries where H. pylori infection and gastric cancer are very prevalent, strategies aimed at analyzing the susceptibility of certain strains to antimicrobials and identifying which genes are responsible for this resistance may be the key to controlling the infection and, therefore, to reducing gastric cancer cases. CONCLUSION: Eradication of H. pylori decreases the incidence of gastric adenocarcinoma. Thus, screening and treating these infections in populations with a high prevalence of H. pylori is beneficial to prevent gastric cancer, with public health in mind.

Unveiling the distinctive variations in multi-omics triggered by TP53 mutation in lung cancer subtypes: An insight from interaction among intratumoral microbiota, tumor microenvironment, and pathology

The TP53 mutation is one of the most common gene mutations in non-small cell lung cancer (NSCLC) and plays a significant role in the occurrence, development, and prognosis of both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Recent studies have also suggested the predictive value of TP53 mutations in the response to immunotherapy for NSCLC. It is known that intratumoral microbiota, tumor immune microenvironment (TIME) and histology are associated with the roles of TP53 mutation in NSCLC. However, the intrinsic associations among these three factors and their underlying interaction with TP53 mutation are not well understood. Additionally, the potential of predicting TP53 mutations using deep learning methods has not yet been fully evaluated. In this paper, we comprehensively evaluated the tissue microbiome, host gene expression characteristics, and histopathological slides of 992 NSCLC patients obtained from the cancer genome atlas (TCGA) and validated the findings using multi-omics data of 332 NSCLC patients from the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Compared to LUSC, LUAD exhibited more substantial differences between patients with and without TP53 mutation in all three aspects. In LUAD, our results imply underlying links between the tissue microbiome and immune cell components in the TIME, and show that the abundance of immune cells is reflected in histology slides. Furthermore, we propose a novel multimodal deep learning model that focuses on histopathology images, which achieves an area under the curve (AUC) of 0.84 in LUAD. In summary, TP53 mutation of LUAD resulted more significant changes in intratumoral microbiota, TIME and histology than that of LUSC. And histopathology images can be used to predict TP53 mutation in LUAD with reasonable accuracy.

Inflammation Mediated by Gut Microbiome Alterations Promotes Lung Cancer Development and an Immunosuppressed Tumor Microenvironment.

Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely coupled with tobacco-associated lung adenocarcinoma in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice exacerbates protumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on lung adenocarcinoma development remains poorly understood. In this study, we investigated the role of gut microbiome changes in lung adenocarcinoma development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of proinflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with lung adenocarcinoma with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in lung adenocarcinoma and present new potential targets for interception and therapy.

Cytomorphological and histomorphological features of lung adenocarcinoma with epidermal growth factor receptor mutation and anaplastic lymphoma kinase gene rearrangement.

Lung cancer is among the lethal and most prevalent oncological diseases globally. It is known that two types of mutations, namely anaplastic lymphoma kinase (ALK) gene rearrangement and epidermal growth factor receptor (EGFR) gene mutation, are responsible for the development of lung adenocarcinoma. The present study aimed to investigate the differences in the frequency of clinical, cytomorphological and histomorphological features of ALK and EGFR-positive lung adenocarcinomas. The present retrospective study comprised 101 patients diagnosed with lung adenocarcinoma. Based on the molecular findings, the patients were categorized into three groups as follows: The ALK-rearranged group (n=28), the EGFR group (n=42) and the negative group (n=31). The clinical features analyzed included sex, age, smoking status and disease stage. The cytomorphological and histomorphological features examined encompassed the following: Cell cluster size, the arrangement of tumor cells, the size of nuclei, nuclear atypia, the visibility of nucleoli, the presence of necrosis, intracytoplasmic vacuoles, signet ring cells, stromal characteristics and the presence of inflammatory infiltrate presence. The results indicated that the female sex was more prevalent in the EGFR group, but statistically significant differences (P<0.05) were observed between the EGFR and negative group. A significantly greater percentage of non-smokers was identified in the EGFR group compared with the ALK group (P<0.01). The majority of patients with confirmed ALK or EGFR mutations received onco-specific treatment. Focal and abundant necrosis was significantly less common in cytological samples in the EGFR group than in the other groups (21.43 vs. 57.14 and 51.61%, combined, P<0.01). No significant differences were observed in other cytomorphological features between the groups. Intracytoplasmic vacuoles, signet ring cells and cells with visible nucleoli were significantly more frequent in histological specimens of the ALK group (P<0.01). The predictive model composed of these features or combined with sex and smoking habits exhibited statistically significant differences for mutation status as a criterion (P<0.01). Collectively, the findings of the present study confirmed that, in addition to clinical characteristics, certain cytological and histological features of lung adenocarcinoma are associated with the mutational status of the tumor.

Association between Helicobacter pylori infection and gastric adenocarcinoma: a retrospective and comparative analysis

The Helicobacter pylori infection increases the risk of development gastric neoplasia. This is the most important risk factor for causing intestinal adenocarcinoma, which is the most prevalent gastric cancer, and is also strongly associated with mucosa-associated lymphoid tissue lymphoma - MALT. A retrospective and comparative analysis was carried out at Hospital de Amor de Barretos, a reference oncology service, in the years 2017 and 2021, in order to determine whether there is an association between the existence of the infection and gastric adenocarcinoma, and whether there was any change over 05 years. In total, 369 medical records of patients diagnosed with gastric cancer were analyzed, 218 and 151, respectively. In 2017, 45.1% of patients were investigated for Helicobacter pylori and 54% in 2021 (p=0.104). Infection was detected in 42.3 and 33.3% (p=0.232) respectively, and eradication therapy in 19.5 and 24%. Although the present study was carried out in a referral oncology hospital, it was not possible to objectively determine the relationship between Helicobacter pylori infection and the development of gastric adenocarcinoma.