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Background: An increasing number of studies have demonstrated that differentially expressed circular RNAs (circRNAs) play critical roles in carcinogenesis. However, the biological function and clinical significance of hsa_circ_0005927 during gastric carcinogenesis remain unclear. The aim of this study was to investigate the acting mechanism and clinical significance of hsa_circ_0005927 in the invasion and metastasis of gastric cancer (GC). Methods: Hsa_circ_0005927 was detected in GC tissues, plasma and gastric juice from patients with GC, and its correlations with clinicopathological parameters were investigated. Receiver operating characteristic curves, Kaplan-Meier survival curves and a prognostic nomogram model were generated to analyze the diagnostic and prognostic value. Real-time cell analyzer, plate colony formation, and Transwell migration and invasion assays were utilized to assess GC cell proliferation, migration and invasion, respectively. Nucleoplasmic separation was applied to determine the distribution of hsa_circ_0005927 in cells. TargetScan and miRanda software were used for target microRNA (miRNA) prediction. Transcriptome sequencing and bioinformatics analysis were performed to annotate the functions of hsa_circ_0005927 in gastric carcinogenesis and metastasis from an RNomic perspective. Key target genes and immune cell infiltrations were analysed. Results: Hsa_circ_0005927 was found downregulated in high-grade intraepithelial neoplasia (HGIEN) tissues and GC tissues. Hsa_circ_0005927 levels in GC tissues were negatively correlated not only with lymphatic metastasis and distal metastasis but also with overall survival and disease-free survival. As a screening biomarker for GC, plasma hsa_circ_0005927 levels significantly increased in the early stages of GC, with a sensitivity and specificity of 52.38% and 76.19%, respectively. Hsa_circ_0005927 was mainly distributed in the cytoplasm, and structurally, it possesses multiple miRNA response elements (MREs) that interact with five miRNAs. A total of 421 downstream target genes of hsa_circ_0005927 were identified by transcriptome sequencing; and bioinformatics analysis suggested that these genes were involved mainly in the negative regulation of the T-cell apoptotic process, the interleukin-27-mediated signaling pathway, growth factor activity, guanylate cyclase activity, transcriptional misregulation in cancer, the cGMP-PKG signaling pathway, and the GnRH signaling pathway during gastric carcinogenesis and metastasis. GUCY1A2 and STK32A are key target genes significantly associated with immune infiltration. Conclusion: Our study revealed that hsa_circ_0005927 is a new player related to the invasion and metastasis of GC and is a potential indicator for early GC screening.
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BACKGROUND: The incidence of Barrett's esophagus (BE) in China is lower compared to the Western populations. Hence, studies conducted in the Chinese population has been limited. The current treatment options available for BE treatment includes argon plasma coagulation (APC), radiofrequency ablation and cryoablation, all with varying degrees of success. AIM: To determine the efficacy and safety of HybridAPC in the treatment of BE. METHODS: The study cohort consisted of patients with BE who underwent HybridAPC ablation treatment. These procedures were performed by seven endoscopists from different tertiary hospitals. The duration of the procedure, curative rate, complications and recurrent rate by 1-year follow-up were recorded. RESULTS: Eighty individuals were enrolled for treatment from July 2017 to June 2020, comprising of 39 males and 41 females with a median age of 54 years (range, 30 to 83 years). The technical success rate of HybridAPC was 100% and the overall curative rate was 98.15%. No severe complications occurred during the operation. BE cases were classified as short-segment BE and long-segment BE. Patients with short-segment BE were all considered cured without complications. Thirty-six patients completed the one-year follow-up without recurrence. Twenty-four percent had mild dysplasia which were all resolved with one post-procedural treatment. The mean duration of the procedure was 10.94 ± 6.52 min. CONCLUSION: Treatment of BE with HybridAPC was found to be a simple and quick procedure that is safe and effective during the short-term follow-up, especially in cases of short-segment BE. This technique could be considered as a feasible alternative ablation therapy for BE.
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Gastric cancer is a prevalent malignancy that poses a serious threat to global health. Despite advances in medical technologies, screening methods, and public awareness, gastric cancer remains a significant cause of morbidity and mortality worldwide. Early gastric cancer frequently does not present with characteristic symptoms, while advanced stage disease is characterized by a dismal prognosis. As such, early screening in gastric cancer is of great importance. In recent years, advances have been made globally in both clinical and basic research for the screening of early gastric cancer. The current predominant screening methods for early gastric cancer include imaging screening, endoscopic screening and serum biomarker screening. Imaging screening encompasses upper gastrointestinal barium meal, multidimensional spiral computed tomography (MDCT), Magnetic resonance imaging (MRI), and ultrasonography. Endoscopic screening methods include white light endoscopy, chromoendoscopy, computed virtual chromoendoscopy, and other endoscopic techniques like endocytoscopy, confocal laser endomicroscopy, optical coherence tomography and so on. Biomarkers screening involves the assessment of conventional biomarkers such as CEA, CA19-9 and CA72-4 as well as more emerging biomarkers such as peptides (PG, G-17, GCAA, TAAs and others), DNA (cfDNA, DNA methylation, MSI), noncoding RNA (miRNA, lncRNA, circRNA, and tsRNA) and others. Each screening method has its strengths and limitations. This article systematically summarizes worldwide progress and future development of early gastric cancer screening methods to provide new perspectives and approaches for early diagnostic and treatment advancements in gastric cancer worldwide.
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Background: Human aldo-keto reductase family 1 member C3 (AKR1C3) is an important molecule that participates in multiple physiological metabolic processes. However, its expression, biological functions and clinical significance in gastric carcinogenesis are unclear. Methods: We collected data from several public data portals and clinical samples and systematically analyzed the clinical significance of tissue and plasma AKR1C3 expression. Then, we filtered prognostic risk factors and established novel prognosis-related nomogram models for predicting overall survival time and postoperative recurrence risk. The application value of the nomogram models was further assessed using clinical samples. Moreover, we explored the potential biological functions of AKR1C3 in gastric carcinogenesis and metastasis through multiomics functional analysis and immune infiltration analysis. Results: AKR1C3 levels were reduced in cancer tissue but increased significantly in the plasma of GC patients; AKR1C3 expression in either sample type was closely associated with multiple clinicopathological characteristics. By combining clinicopathological factors and AKR1C3 levels, two novel nomogram models were developed to predict overall survival time and postoperative recurrence risk. Multiomics functional analysis revealed that when its expression is dysregulated, AKR1C3 can widely participate in gene expression regulation through multiple regulatory modes at the gene, RNA and protein levels and exert various crucial biological effects in carcinogenesis and metastasis. Moreover, AKR1C3 expression was correlated with the infiltration of several immune cell types, and AKR1C3 was predicted to interact with several clinical drugs. Conclusion: Dysregulated AKR1C3 expression is related to gastric carcinogenesis and immunotherapy response and is a promising biomarker and effective biotherapy target in GC.
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Helicobacter pylori (H. pylori) resistance is the most important risk factor for eradication failure. However, in most regions, antibiotic resistance rates of H. pylori in patients with different types of gastric mucosal lesions are still unclear. An 8-year clinical retrospective cohort study involving 2847 patients was performed. In this study, we first summarized and compared the resistance status of H. pylori in different years, ages, sexes, and gastric diseases. The resistance profiles of amoxicillin (AMX), clarithromycin (CLR), levofloxacin (LVX) and furazolidone (FR) and their changing trends in the clinic were described. Then, multiple antibiotic resistance in different gastric diseases and years were described and compared. The relationship between proton pump inhibitor (PPI) medication history and antibiotic resistance in H. pylori was also explored. Finally, an antibiotic resistance risk model was constructed for clinical resistance risk prediction. The overall resistance rates of AMX, CLR, LVX and FR in gastric diseases were 8.18%, 38.11%, 43.98%, and 13.73%, respectively. The mono resistance, double resistance, triple resistance, and quadruple resistance rates were 30.17%, 25.96%, 6.46%, and 0.63%, respectively. Compared with the period from 2014 to 2016, the rates of mono-resistance and multiple resistance all showed relatively downward trends in the past 5 years. Factors including age, sex, type of gastric lesions and recent PPI treatment history are associated with the antibiotic resistance rate of H. pylori. Atrophic gastritis is an important clinical feature of high-risk antibiotic resistance in H. pylori-infected patients. Patients with atrophic gastritis have higher risk of resistant strains infection. In this study, our data provide the association between antibiotic resistance of H. pylori and gastritis pattern, which indicate the higher risk of resistant strain infection if the patients with atrophic gastritis, PPI history and older age.
Subject(s)
Gastritis, Atrophic , Helicobacter Infections , Helicobacter pylori , Stomach Diseases , Humans , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Helicobacter Infections/drug therapy , Helicobacter Infections/epidemiology , Retrospective Studies , Amoxicillin/pharmacology , Clarithromycin/therapeutic use , Stomach Diseases/drug therapy , Levofloxacin/pharmacology , Proton Pump Inhibitors/therapeutic use , Proton Pump Inhibitors/pharmacology , Furazolidone/pharmacology , Furazolidone/therapeutic use , Drug Resistance, Bacterial , Metronidazole/pharmacologyABSTRACT
Colorectal cancer (CRC) is a prevalent clinical malignancy of the gastrointestinal system, and its clinical drug resistance is the leading cause of poor prognosis. Mechanistically, CRC cells possess a specific oxidative stress defense mechanism composed of a significant number of endogenous antioxidants, such as glutathione, to combat the damage produced by drug-induced excessive reactive oxygen species (ROS). We report on a new anti-CRC nanoplatform, a multifunctional chemo-photothermal nanoplatform based on Camptothecin (CPT) and IR820, an indocyanine dye. The implementation of a GSH-triggered ferroptosis-integrated tumor chemo-photothermal nanoplatform successfully addressed the poor targeting ability of CPT and IR820 while exhibiting significant growth inhibitory effects on CRC cells. Mechanistically, to offset the oxidative stress created by the broken SeSe bonds, endogenous GSH was continuously depleted, which inactivated GPX4 to accumulate lipid peroxides and induce ferroptosis. Concurrently, exogenously administered linoleic acid was oxidized under photothermal conditions, resulting in an increase in LPO accumulation. With the breakdown of the oxidative stress defense system, chemotherapeutic efficacy could be effectively enhanced. In combination with photoacoustic imaging, the nanoplatform could eradicate solid tumors by means of ferroptosis-sensitized chemotherapy. This study indicates that chemotherapy involving a ferroptosis mechanism is a viable method for the treatment of CRC.
Subject(s)
Colorectal Neoplasms , Ferroptosis , Humans , Oxidative Stress , Glutathione , Colorectal Neoplasms/drug therapyABSTRACT
BACKGROUND: Esophageal strictures significantly impair patient quality of life and present a therapeutic challenge, particularly due to the high recurrence post-ESD/EMR. Current treatments manage symptoms rather than addressing the disease's etiology. This review concentrates on the mechanisms of esophageal stricture formation and recurrence, seeking to highlight areas for potential therapeutic intervention. METHODS: A literature search was conducted through PUBMED using search terms: esophageal stricture, mucosal resection, submucosal dissection. Relevant articles were identified through manual review with reference lists reviewed for additional articles. RESULTS: Preclinical studies and data from animal studies suggest that the mechanisms that may lead to esophageal stricture include overdifferentiation of fibroblasts, inflammatory response that is not healed in time, impaired epithelial barrier function, and multimethod factors leading to it. Dysfunction of the epithelial barrier may be the initiating mechanism for esophageal stricture. Achieving perfect in-epithelialization by tissue-engineered fabrication of cell patches has been shown to be effective in the treatment and prevention of esophageal strictures. CONCLUSION: The development of esophageal stricture involves three stages: structural damage to the esophageal epithelial barrier (EEB), chronic inflammation, and severe fibrosis, in which dysfunction or damage to the EEB is the initiating mechanism leading to esophageal stricture. Re-epithelialization is essential for the treatment and prevention of esophageal stricture. This information will help clinicians or scientists to develop effective techniques to treat esophageal stricture in the future.
Subject(s)
Esophageal Neoplasms , Esophageal Stenosis , Animals , Humans , Esophageal Stenosis/therapy , Esophageal Stenosis/prevention & control , Esophagoscopy/adverse effects , Esophagoscopy/methods , Constriction, Pathologic/complications , Quality of LifeABSTRACT
Objective@#To explore the interaction of multi-target stool DNA (MT-sDNA), intestinal flora and environmental factors in the development of colorectal cancer, so as to provide insights into pathogenesis study of colorectal cancer.@*Methods@#A total of 54 cases of colorectal cancer from the First Affiliated Hospital of Ningbo University were included in the case group and 51 healthy subjects were included in the control group. Demographic information, diet and family history of colorectal cancer were collected by a questionnaire survey. MT-sDNA, intestinal flora, cancer antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA) and other tumor markers were detected. Interactions of MT-sDNA, intestinal flora and environmental factors with the development of colorectal cancer was analyzed by multifactor dimensionality reduction (MDR), crossover analysis and additive model.@*Results@#The case group included 20 males (37.04%) and 34 females (62.96%), and had a mean age of (64.89±9.72) years. The control group included 24 males (47.06%) and 27 females (52.94%), and had a mean age of (53.94±10.33) years. MDR analysis showed that subjects with both high absolute intestinal flora indexes and positive MT-sDNA had an increased risk of colorectal cancer (OR=3.782, 95%CI: 1.190-5.034). Crossover analysis showed that subjects with positive MT-sDNA and >5 μg/L of CEA had an increased risk of colorectal cancer (OR=2.121, 95%CI: 1.162-4.033). Additive model analysis showed that MT-sDNA had positive additive interaction with CEA (SI=3.687, 95%CI: 1.229-7.238), and MT-sDNA had negative additive interaction with fruit intake (SI=0.145, 95%CI: 0.020-0.753).@*Conclusion@#Positive MT-sDNA can synergistically increase the risk of colorectal cancer with high intestinal flora index and CEA, and fruit intake can reduce the risk of colorectal cancer in MT-sDNA-positive population.
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Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.
Subject(s)
Carcinoma, Hepatocellular , Jaundice, Obstructive , Liver Neoplasms , Thrombosis , Female , Humans , Middle Aged , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/diagnostic imaging , Jaundice, Obstructive/etiology , Liver Neoplasms/diagnosis , Liver Neoplasms/diagnostic imaging , Hepatic Duct, Common/pathology , Thrombosis/diagnostic imaging , Thrombosis/complications , Hemorrhage/complicationsABSTRACT
Background: Endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) does not always lead to curative resection. Risk factors of lymph node metastasis (LNM)/local cancer residue after non-curative ESD for EGC have not been fully elucidated. We therefore aimed to clarify them and evaluate whether the "eCura system" is reliable for the risk stratification of LNM after non-curative ESD. Methods: We conducted a multicenter retrospective study at seven institutions in Zhejiang, China, on 128 patients who underwent non-curative ESD for EGC. We divided the patients into two groups according to their therapeutic regimen after non-curative ESD. We analyzed the risk factors for LNM, local cancer residue, cancer recurrence, and cancer-specific mortality. Furthermore, we compared the outcomes in each risk category after applying the "eCura system". Results: Among 68 patients undergoing additional surgery, LNM was found in three (4.41%) patients, while local cancer residue was found in eight (11.76%) patients. Multivariate analysis showed that upper third location and deep submucosal invasion were independent risk factors of LNM and local cancer residue. Among 60 patients who underwent simple follow-up, local cancer recurrence was found in four (6.67%) patients and cancer-specific mortality was found in one (1.67%) patient. There were no independent risk factors of cancer recurrence and cancer-specific mortality in our study. During the follow-up period, 5-year overall survival (OS) and disease-free survival (DFS) were 93.8% and 88.9%, respectively. Additionally, LNM and cancer recurrence were significantly associated with the eCura scoring system (p = 0.044 and p = 0.017, respectively), while local cancer residue and cancer-specific mortality were not (p = 0.478 and p = 0.131, respectively). Conclusion: Clinicians should be aware of the risk factors for the prognosis of patients with non-curative ESD to determine subsequent treatment. Through the application of the "eCura system", additional surgery should be performed in patients with intermediate/high risk of LNM.
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BACKGROUND: Colorectal cancer (CRC) is a major global health burden. The current diagnostic tests have shortcomings of being invasive and low accuracy. AIM: To explore the combination of intestinal microbiome composition and multi-target stool DNA (MT-sDNA) test in the diagnosis of CRC. METHODS: We assessed the performance of the MT-sDNA test based on a hospital clinical trial. The intestinal microbiota was tested using 16S rRNA gene sequencing. This case-control study enrolled 54 CRC patients and 51 healthy controls. We identified biomarkers of bacterial structure, analyzed the relationship between different tumor markers and the relative abundance of related flora components, and distinguished CRC patients from healthy subjects by the linear discriminant analysis effect size, redundancy analysis, and random forest analysis. RESULTS: MT-sDNA was associated with Bacteroides. MT-sDNA and carcinoembryonic antigen (CEA) were positively correlated with the existence of Parabacteroides, and alpha-fetoprotein (AFP) was positively associated with Faecalibacterium and Megamonas. In the random forest model, the existence of Streptococcus, Escherichia, Chitinophaga, Parasutterella, Lachnospira, and Romboutsia can distinguish CRC from health controls. The diagnostic accuracy of MT-sDNA combined with the six genera and CEA in the diagnosis of CRC was 97.1%, with a sensitivity and specificity of 98.1% and 92.3%, respectively. CONCLUSION: There is a positive correlation of MT-sDNA, CEA, and AFP with intestinal microbiome. Eight biomarkers including six genera of gut microbiota, MT-sDNA, and CEA showed a prominent sensitivity and specificity for CRC prediction, which could be used as a non-invasive method for improving the diagnostic accuracy for this malignancy.
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BACKGROUND: Worldwide, gastric cancer (GC) is a common lethal solid malignancy with a poor prognosis. Cuproptosis is a novel type of cell death mediated by protein lipoylation and may be related to GC prognosis. AIM: To offer new insights to predict GC prognosis and provide multiple therapeutic targets related to cuproptosis-related genes (CRGs) for future therapy. METHODS: We collected data from several public data portals, systematically estimated the expression level and prognostic values of CRGs in GC samples, and investigated related mechanisms using public databases and bioinformatics. RESULTS: Our results revealed that FDX1, LIAS, and MTF1 were differentially expressed in GC samples and exhibited important prognostic significance in The Cancer Genome Atlas (TCGA) cohort. We constructed a nomogram model for overall survival and disease-specific survival prediction and validated it via calibration plots. Mecha-nistically, immune cell infiltration and DNA methylation prominently affected the survival time of GC patients. Moreover, protein-protein interaction network, KEGG pathway and gene ontology enrichment analyses demonstrated that FDX1, LIAS, MTF1 and related proteins play key roles in the tricarboxylic acid cycle and cuproptosis. Gene Expression Omnibus database validation showed that the expression levels of FDX1, LIAS, and MTF1 were consistent with those in the TCGA cohort. Top 10 perturbagens has been filtered by Connectivity Map. CONCLUSION: In conclusion, FDX1, LIAS, and MTF1 could serve as potential prognostic biomarkers for GC patients and provide novel targets for immunotarget therapy.
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Gastric cancer (GC) is a particularly malignant disease; thus, early diagnosis and treatment are especially important. Transfer RNA-derived small RNAs (tsRNAs) have been implicated in the onset and progression of various cancers. Therefore, the aim of this study was to explore the role of tRF-18-79MP9P04 (previously named tRF-5026a) in the onset and progression of GC. Expression levels of tRF-18-79MP9P04 were quantified in gastric mucosa specimens of healthy controls and plasma samples of patients with different stages of GC. The results showed that plasma levels of tRF-18-79MP9P04 were significantly decreased in the early and advanced stages of GC. The results of the nucleocytoplasmic separation assay found that tRF-18-79MP9P04 was localized in the nuclei of GC cells. High-throughput transcriptome sequencing identified genes regulated by tRF-18-79MP9P04 in GC cells, and the function of tRF-18-79MP9P04 was predicted by bioinformatics. Collectively, the findings of this study suggest that tRF-18-79MP9P04 would be useful as non-invasive biomarker for early diagnosis of GC and is related to cornification, the type I interferon signaling pathway, RNA polymerase II activities, and DNA binding.
Subject(s)
Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , RNA, Transfer/genetics , RNA, Transfer/metabolism , BiomarkersABSTRACT
BACKGROUND: Gastric cancer (GC) carries significant morbidity and mortality globally. An increasing number of studies have confirmed that circular RNA (circRNA) is tightly associated with the carcinogenesis and development of GC, especially acting as a competing endogenous RNA for miRNAs. OBJECTIVE: Our study aimed to construct the circRNA-miRNA-mRNA regulatory network and analyze the function and prognostic significance of the network using bioinformatics tools. METHODS: We first downloaded the GC expression profile from the Gene Expression Omnibus database and identified differentially expressed genes and differentially expressed circRNAs. Then, we predicted the miRNA-mRNA interaction pairs and constructed the circRNA-miRNA-mRNA regulatory network. Next, we established a protein-protein interaction network and analyzed the function of these networks. Finally, we primarily validated our results by comparison with The Cancer Genome Atlas cohort and by performing qRT-PCR. RESULTS: We screened the top 15 hub genes and 3 core modules. Functional analysis showed that in the upregulated circRNA network, 15 hub genes were correlated with extracellular matrix organization and interaction. The function of downregulated circRNAs converged on physiological functions, such as protein processing, energy metabolism and gastric acid secretion. We ascertained 3 prognostic and immune infiltration-related genes, COL12A1, COL5A2, and THBS1, and built a nomogram for clinical application. We validated the expression level and diagnostic performance of key prognostic differentially expressed genes. CONCLUSIONS: In conclusion, we constructed two circRNA-miRNA-mRNA regulatory networks and identified 3 prognostic and screening biomarkers, COL12A1, COL5A2, and THBS1. The ceRNA network and these genes could play important roles in GC development, diagnosis and prognosis.
Subject(s)
MicroRNAs , Stomach Neoplasms , Humans , MicroRNAs/genetics , RNA, Circular/genetics , Stomach Neoplasms/genetics , RNA, Messenger/genetics , PrognosisABSTRACT
Background: The transition from a healthy gastric mucosa to gastric cancer is a multi-step process. Early screening can significantly improve the survival rate of gastric cancer patients. A reliable liquid biopsy for gastric cancer prediction is urgently needed and since tRNA-derived fragments (tRFs) are abundant in various body fluids, tRFs are possible new biomarkers for gastric cancer. Methods: A total of 438 plasma samples from patients with different gastric mucosal lesions as well as healthy individuals were collected. A specific reverse transcription primer, a forward primer, a reverse primer, and a TaqMan probe were designed. A standard curve was constructed and an absolute quantitation method was devised for detection of tRF-33-P4R8YP9LON4VDP in plasma samples of individuals with differing gastric mucosa lesions. Receiver operating characteristic curves were constructed to evaluate the diagnostic values of tRF-33-P4R8YP9LON4VDP for individual with differing gastric mucosa. A Kaplan-Meier curve was established to calculate the prognostic value of tRF-33-P4R8YP9LON4VDP for advanced gastric cancer patients. Finally, a multivariate Cox regression analysis was performed to assess the independent prognostic value of tRF-33-P4R8YP9LON4VDP for advanced gastric cancer patients. Results: A detection method for plasma tRF-33-P4R8YP9LON4VDP was successfully established. Levels of plasma tRF-33-P4R8YP9LON4VDP were shown to reflect a gradient change from healthy individuals to gastritis patients to early and advanced gastric cancer patients. Significant differences were found among individuals with differing gastric mucosa, with reduced levels of tRF-33-P4R8YP9LON4VDP significantly related to a poor prognosis. tRF-33-P4R8YP9LON4VDP was found to be an independent predictor of an unfavorable survival outcome. Conclusions: In this study, we developed a quantitative detection method for plasma tRF-33-P4R8YP9LON4VDP that exhibited hypersensitivity, convenience, and specificity. Detection of tRF-33-P4R8YP9LON4VDP was found to be a valuable means by which to monitor different gastric mucosa and to predict patient prognosis.
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Background: Hepatocellular carcinoma (HCC) remains notorious for its high malignancy, poor prognosis and high mortality. The exploration of novel therapeutic agents for HCC has remained challenging due to its complex aetiology. Therefore, it is necessary to elucidate the pathogenesis and mechanism of HCC for clinical intervention. Methods: We collected data from several public data portals and systematically analysed the association between transcription factors (TFs), eRNA-associated enhancers and downstream targets. We next filtered the prognostic genes and established a novel prognosis-related nomogram model. Moreover, we explored the potential mechanisms of the identified prognostic genes. The expression level was validated by several ways. Results: We first constructed a significant TF-enhancer-target regulatory network and identified DAPK1 as a coregulatory differentially expressed prognosis-related gene. We combined common clinicopathological factors and built a prognostic nomogram model for HCC. We found that our regulatory network was correlated with the processes of synthesizing various substances. Moreover, we explored the role of DAPK1 in HCC and found that it was associated with immune cell infiltration and DNA methylation. Several immunostimulators and targeting drugs could be promising immune therapy targets. The tumor immune microenvironment was analyzed. Finally, the lower DAPK1 expression in HCC was validated via the GEO database, UALCAN cohort, and qRT-PCR. Conclusion: In conclusion, we established a significant TF-enhancer-target regulatory network and identified downregulated DAPK1 as an important prognostic and diagnostic gene in HCC. Its potential biological functions and mechanisms were annotated using bioinformatics tools.
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Gastric cancer (GC) is one of the most common malignancies worldwide. Patients with advanced GC need palliative care to ensure survival. This includes the use of chemotherapy agents, such as cisplatin, 5-fluorouracil, oxaliplatin, paclitaxel, and pemetrexed, as well as targeted agents. However, the emergence of drug resistance evidence in poor patient outcomes and poor prognosis is a motivation to determine the specific mechanism of drug resistance. Interestingly, circular RNAs (circRNAs) play an important part in the carcinogenesis and progression of GC and are involved in GC drug resistance. This review systematically summarizes the functions and mechanisms of circRNAs underlying GC drug resistance, especially chemoresistance. It also emphasizes that circRNAs can serve as promising targets for improving drug resistance and therapeutic efficacy.
Subject(s)
RNA, Circular , Stomach Neoplasms , Humans , RNA, Circular/genetics , Stomach Neoplasms/drug therapy , Stomach Neoplasms/genetics , Drug Resistance, Neoplasm/genetics , Cisplatin/therapeutic use , Fluorouracil/therapeutic useABSTRACT
Increasing rates of Helicobacter pylori resistance are associated with multiple clinical challenges. Bacterial factors linked to H. pylori resistance are mutations, efflux pumps, and biofilms. Gene mutations such as nucleic acid synthesis-related gene mutations, rRNA coding gene mutations, and cell wall synthesis-related gene mutations are the most important mechanisms by which H. pylori evades bactericidal effects. These mechanisms are also closely related to the biological activity of the efflux pump systems and biofilms. Activation of the efflux pump system and biofilm formation both lead to the emergence of MDR strains, further increasing the difficulty of eradication therapy. In this review, the status of antibiotic resistance in H. pylori from different regions and countries is summarized and compared, and H. pylori resistance profiles and their changing trends in the clinic are described. Then, research progress on biomolecular mechanisms underlying antibiotic resistance, diagnostic methods, and treatment strategies are introduced and discussed. Challenges resulting from increasing resistance, potential solutions to combat increasing resistance, and future directions are discussed to help clinicians and researchers better address the emergence and spread of resistant H. pylori strains and optimize drug regimens. With the rate of H. pylori resistance to commonly used antibiotics increasing, more attention should be given to the selection of antibiotics and to monitoring resistance when antibiotics are used for clinical eradication treatment. Individualized precise eradication treatment under the guidance of drug susceptibility testing will become the mainstream method of treatment in the future.
Subject(s)
Helicobacter Infections , Helicobacter pylori , Mycobacterium tuberculosis , Humans , Helicobacter pylori/genetics , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Drug Resistance, Bacterial/genetics , Clarithromycin/pharmacology , Metronidazole/pharmacology , Metronidazole/therapeutic useABSTRACT
Gastric cancer (GC) is a serious disease with high mortality and poor prognosis. It is known that tRNA halves play key roles in the progression of cancer. This study explored the function of the tRNA half tRF-41-YDLBRY73W0K5KKOVD in GC. Quantitative real-time reverse transcription-polymerase chain reaction was used to measure RNA levels. The level of tRF-41-YDLBRY73W0K5KKOVD in GC cells was regulated by its mimics or inhibitor. Cell proliferation was evaluated by using a Cell Counting Kit-8 and EdU cell proliferation assay. A Transwell assay was used to detect cell migration. Flow cytometry was used to measure cell cycle and apoptosis. The results showed that tRF-41-YDLBRY73W0K5KKOVD expression was decreased in GC cells and tissues. Functionally, overexpression of tRF-41-YDLBRY73W0K5KKOVD inhibited cell proliferation, reduced migration, repressed the cell cycle, and promoted cell apoptosis in GC cells. Based on RNA sequencing results and luciferase reporter assays, 3'-phosphoadenosine-5'-phosphosulfate synthase 2 (PAPSS2) was identified as a target gene of tRF-41-YDLBRY73W0K5KKOVD. These findings indicated that tRF-41-YDLBRY73W0K5KKOVD inhibited GC progression, suggesting that tRF-41-YDLBRY73W0K5KKOVD might be a potential therapeutic target in GC.
Subject(s)
Biomarkers, Tumor , Disease Progression , RNA, Transfer , Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , RNA, Transfer/metabolism , Real-Time Polymerase Chain Reaction , Cell Proliferation , Cell Count , Cell Movement , Apoptosis , Multienzyme Complexes/genetics , Sulfate Adenylyltransferase/genetics , Gene Expression Regulation, Neoplastic , Male , Female , Adult , Middle Aged , Biomarkers, Tumor/metabolismABSTRACT
The heterogeneous species of tRNA-derived fragments (tRFs) with specific biological functions was recently identified. Distinct roles of tRFs in tumor development and viral infection, mediated through transcriptional and post-transcriptional regulation, has been demonstrated. In this review, we briefly summarize the current literatures on the classification of tRFs and the effects of tRNA modification on tRF biogenesis. Moreover, we highlight the tRF repertoire of biological roles such as gene silencing, and regulation of translation, cell apoptosis, and epigenetics. We also summarize the biological roles of various tRFs in cancer development and viral infection, their potential value as diagnostic and prognostic biomarkers for different types of cancers, and their potential use in cancer therapy.