Genomic characterization and risk stratification of esophageal squamous dysplasia.

Objectives: The majority of esophageal squamous dysplasia (ESD) patients progress slowly, while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment. However, the molecular mechanisms underlying these clinical observations are still largely unknown. Methods: By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma (ESCC) patients, we demonstrated lower somatic mutation and copy number alteration (CNA) burden in ESD compared with ESCC. Results: Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD progression. Furthermore, we revealed that miR-4292 promoted ESD progression and could serve as a non-invasive diagnostic marker for ESD. Conclusions: These findings largely expanded our understanding of ESD genetics and tumorigenesis, which possessed promising significance for improving early diagnosis, reducing overtreatment, and identifying high-risk ESD patients.

Pharmacologically inducing anoikis offers novel therapeutic opportunities in hepatocellular carcinoma.

Tumor metastasis occurs in hepatocellular carcinoma (HCC), leading to tumor progression and therapeutic failure. Anoikis is a matrix detachment-induced apoptosis, also known as detachment-induced cell death, and mechanistically prevents tumor cells from escaping their native extracellular matrix to metastasize to new organs. Deciphering the regulators and mechanisms of anoikis in cancer metastasis is urgently needed to treat HCC. Several natural and synthetic products induce anoikis in HCC cells and in vivo models. Here, we first briefly summarize the current understanding of the molecular mechanisms of anoikis regulation and relevant regulators involved in HCC metastasis. Then we discuss the therapeutic potential of pharmacological induction of anoikis as a potential treatment against HCC. Finally, we discuss the key limitations of this therapeutic paradigm and propose possible strategies to overcome them. Cumulatively this review suggests that the pharmacological induction of anoikis can be used a promising therapeutic modality against HCC.

Periplcymarin targets glycolysis and mitochondrial oxidative phosphorylation of esophageal squamous cell carcinoma: Implication in anti-cancer therapy.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer (EC) in China, and demonstrates varying levels of resistance to multiple chemotherapeutic agents. Our previous studies have proved that periplocin (CPP), derived from the extract of cortex periplocae, exhibiting the capacity to hinder proliferation and induce apoptosis in ESCC cells. Several studies have identified additional anti-cancer constituents in the extract of cortex periplocae, named periplcymarin (PPM), sharing similar compound structure with CPP. Nevertheless, the inhibitory effects of PPM on ESCC and their underlying mechanisms remain to be further elucidated. PURPOSE: The aim of this study was to investigate function of PPM inhibiting the growth of ESCC in vivo and in vitro and to explore its underlying mechanism, providing the potential anti-tumor drug for ESCC. METHODS: Initially, a comparative analysis was conducted on the inhibitory activity of three naturally compounds obtained from the extract of cortex periplocae on ESCC cells. Among these compounds, PPM was chosen for subsequent investigation owing to its comparatively structure and anti-tumor activity simultaneously. Subsequently, a series of biological functional experiments were carried out to assess the impact of PPM on the proliferation, apoptosis and cell cycle arrest of ESCC cells in vitro. In order to elucidate the molecular mechanism of PPM, various methodologies were employed, including bioinformatics analyses and mechanistic experiments such as high-performance liquid chromatography combined with mass spectrometry (HPLC-MS), cell glycolysis pressure and mitochondrial pressure test. Additionally, the anti-tumor effects of PPM on ESCC cells and potential toxic side effects were evaluated in vivo using the nude mice xenograft assay. RESULTS: Our study revealed that PPM possesses the ability to impede the proliferation of ESCC cells, induce apoptosis, and arrest the cell cycle of ESCC cells in the G2/M phase in vitro. Mechanistically, PPM exerted its effects by modulating glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), as confirmed by glycolysis pressure and mitochondrial pressure tests. Moreover, rescue assays demonstrated that PPM inhibits glycolysis and OXPHOS in ESCC cells through the PI3K/AKT and MAPK/ERK signaling pathways. Additionally, we substantiated that PPM effectively suppresses the growth of ESCC cells in vivo, with only modest potential toxic side effects. CONCLUSION: Our study provides novel evidence that PPM has the potential to simultaneously target glycolysis and mitochondrial OXPHOS in ESCC cells. This finding highlights the need for further investigation into PPM as a promising therapeutic agent that targets the tumor glucose metabolism pathway in ESCC.

Depletion of CPNE7 sensitizes colorectal cancer to 5-fluorouracil by downregulating ATG9B expression.

We aimed to explore the biological function of CPNE7 and determine the impact of CPNE7 on chemotherapy resistance in colorectal cancer (CRC) patients. According to the Gene Expression Profiling Interactive Analysis database and previously published data, CPNE7 was identified as a potential oncogene in CRC. RT-qPCR and Western blotting were performed to verify the expression of CPNE7. Chi-square test was used to evaluate the associations between CPNE7 and clinical features. Cell proliferation, colony formation, cell migration and invasion, cell cycle and apoptosis were assessed to determine the effects of CPNE7. Transcriptome sequencing was used to identify potential downstream regulatory genes, and gene set enrichment analysis was performed to investigate downstream pathways. The effect of CPNE7 on 5-fluorouracil chemosensitivity was verified by half maximal inhibitory concentration (IC50). Subcutaneous tumorigenesis assay was used to examine the role of CPNE7 in sensitivity of CRC to chemotherapy in vivo. Transmission electron microscopy was used to detect autophagosomes. CPNE7 was highly expressed in CRC tissues, and its expression was correlated with T stage and tumour site. Knockdown of CPNE7 inhibited the proliferation and colony formation of CRC cells and promoted apoptosis. Knockdown of CPNE7 suppressed the expression of ATG9B and enhanced the sensitivity of CRC cells to 5-fluorouracil in vitro and in vivo. Knockdown of CPNE7 reversed the induction of the autophagy pathway by rapamycin and reduced the number of autophagosomes. Depletion of CPNE7 attenuated the malignant proliferation of CRC cells and enhanced the chemosensitivity of CRC cells to 5-fluorouracil.

A model based on immunogenic cell death-related genes predicts prognosis and response to immunotherapy in kidney renal clear cell carcinoma.

Background: The prognosis of patients with kidney renal clear cell carcinoma (KIRC), a life-threatening condition, is poor. Immunogenic cell death (ICD) induces regulated cell death via immunogenic signal secretion and exposure. ICD induces regulated cell death through immunogenic signal secretion and exposure. ICD plays an essential role in tumorigenesis, however, the role of ICD in KIRC remains unclear. Methods: This study examined the expression levels of 34 ICD-related genes in The Cancer Genome Atlas (TCGA) data set. Signature genes linked to KIRC survival were identified using Cox regression. Next, a prognostic risk model (RM) was built. Subsequently, the KIRC patients were divided into low- and high-risk groups. Kaplan-Meier curves and receiver operating characteristic (ROC) curves were plotted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were carried out to investigate the possible role of differential gene expression between the two groups. The immune microenvironment (IME) was assessed using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression, CIBERSORT, and single-sample gene-set enrichment analysis algorithms. An enrichment analysis was used to determine the biological significance of these regulatory networks we conducted. The relationship between immune checkpoint gene expression and risk score, and the relationship between treatment outcome and gene expression were assessed using correlation analyses. Results: We developed a KIRC RM based on five ICD-related genes (i.e., FOXP3, IFNB1, IL6, LY96, and TLR4), which were identified as the prognostic signature genes. Using the TCGA data set, we conducted a survival analysis and found that the 3-year RM had an area under the curve (AUC) of 0.735, which validated the reliability of the signature. Similarly, using the International Cancer Genome Consortium (ICGC) data set, we found that the 3-year RM had an AUC of 0.732. Conclusions: A RM based on five ICD-related genes was built to predict the prognosis of KIRC patients. This RM predicted patient prognosis and reflected the tumor IME of KIRC patients. Thus, this RM could be used to promote individualized treatments and provide potential novel targets for immunotherapy.

Ropivacaine inhibits the malignant behavior of lung cancer cells by regulating retinoblastoma-binding protein 4.

Background: Ropivacaine is a local anesthetic commonly used in regional nerve blocks to manage perioperative pain during lung cancer surgery. Recently, the antitumor potential of ropivacaine has received considerable attention. Our previous study showed that ropivacaine treatment inhibits the malignant behavior of lung cancer cells in vitro. However, the potential targets of ropivacaine in lung cancer cells have not yet been fully identified. This study aimed to explore the antitumor effects and mechanisms of action of ropivacaine in lung cancer. Methods: Lung cancer A549 cells were treated with or without 1 mM ropivacaine for 48 h. Quantitative proteomics was performed to identify the differentially expressed proteins (DEPs) triggered by ropivacaine treatment. STRING and Cytoscape were used to construct protein-protein interaction (PPI) networks and analyze the most significant hub genes. Overexpression plasmids and small interfering RNA were used to modulate the expression of key DEPs in A549 and H1299 cells. MTS, transwell assays, and flow cytometry were performed to determine whether the key DEPs were closely related to the anticancer effect of ropivacaine on the malignant behavior of A549 and H1299 cells. Results: Quantitative proteomic analysis identified 327 DEPs (185 upregulated and 142 downregulated proteins) following ropivacaine treatment. Retinoblastoma-binding protein 4 (RBBP4) was one of the downregulated DEPs and was selected as the hub protein. TCGA database showed that RBBP4 was significantly upregulated in lung cancer and was associated with poor patient prognosis. Inhibition of RBBP4 by siRNA resulted in a significant decrease in the proliferation and invasive capacity of lung cancer cells and the induction of cell cycle arrest. Additionally, the results indicated RBBP4 knockdown enhanced antitumor effect of ropivacaine on A549 and H1299 cells. Conversely, the overexpression of RBBP4 using plasmids reversed the inhibitory effects of ropivacaine. Conclusion: Our data suggest that ropivacaine suppresses lung cancer cell malignancy by downregulating RBBP4 protein expression, which may help clarify the mechanisms underlying the antitumor effects of ropivacaine.

Identification of the immunogenic membrane proteins, catalase, PgbA, and PgbB, as potential antigens against Helicobacter pylori.

AIMS: This study aims to investigate the specific membrane antigens that are targeted by antibodies raised against Helicobacter pylori. METHODS AND RESULTS: Bovine milk antibodies were prepared using whole H. pylori, purified membrane proteins, or both. Enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments revealed that these immunogens triggered anti-H. pylori antibody production in milk. The highest antibody titer was induced by the mixture of whole bacteria and purified membrane proteins. The antibodies induced by mixed immunogens significantly inhibited H. pylori growth in vitro and were used to identify catalase, plasminogen-binding protein A (PgbA), and PgbB via western blotting, immunoprecipitation, and two-dimensional western blotting followed by liquid chromatography with tandem mass spectrophotometry. The immunogenicity of PgbA and PgbB was verified in mice vaccinated with their B-cell epitope vaccines. Following prophylactic vaccination of C57BL/6 mice, each of the three antigens alone and their combination reduced the weight loss in mice, increased antibody titers, and relieved the inflammatory status of the gastric mucosa following H. pylori infection. CONCLUSIONS: Catalase, PgbA, and PgbB could serve as valuable membrane antigens for the development of anti-H. pylori immunotherapies.

LncRNA CCAT1 facilitates the progression of gastric cancer via PTBP1-mediated glycolysis enhancement.

BACKGROUND: Gastric cancer (GC) is one of the most prevalent malignant tumors of the digestive system. As a hallmark of cancer, energy-related metabolic reprogramming is manipulated by multiple factors, including long non-coding RNAs (lncRNAs). Notably, lncRNA CCAT1 has been identified as a crucial regulator in tumor progression. Nevertheless, the precise molecular mechanisms underlying the involvement of CCAT1 in metabolic reprogramming of GC remain unclear. METHODS: Gain- and loss-of-function experiments were performed to evaluate the roles of CCAT1 in tumorigenesis and glycolysis of GC. Bioinformatics analyses and mechanistic experiments, such as mass spectrometry (MS), RNA-pulldown, and RNA immunoprecipitation (RIP), were employed to reveal the potential interacting protein of CCAT1 and elucidate the regulatory mechanism of CCAT1 in GC glycolysis. Moreover, the nude mice xenograft assay was used to evaluate the effect of CCAT1 on GC cells in vivo. RESULTS: In this study, we identified that CCAT1 expression was significantly elevated in the tissues and plasma exosomes of GC patients, as well as GC cell lines. Functional experiments showed that the knockdown of CCAT1 resulted in a substantial decrease in the proliferation, migration and invasion of GC cells both in vitro and in vivo through decreasing the expression of glycolytic enzymes and glycolytic rate. Conversely, overexpression of CCAT1 exhibited contrasting effects. Mechanistically, CCAT1 interacted with PTBP1 and effectively maintained its stability by inhibiting the ubiquitin-mediated degradation process. As a critical splicing factor, PTBP1 facilitated the transition from PKM1 to PKM2, thereby augmenting the glycolytic activity of GC cells and ultimately fostering the progression of GC. CONCLUSIONS: Our findings demonstrate that CCAT1 plays a significant role in promoting the proliferation, migration, and invasion of GC cells through the PTBP1/PKM2/glycolysis pathway, thus suggesting CCAT1's potential as a biomarker and therapeutic target for GC.

Identification of combinatorial miRNA panels derived from extracellular vesicles as biomarkers for esophageal squamous cell carcinoma.

MicroRNAs (miRNAs) are relatively stable in blood, emerging as one of the most promising biomarkers in tumor liquid biopsy. Both total and extracellular vesicles (EVs) encapsulated miRNA have been studied for prognostic potential in a variety of cancers. Here, we systematically compared and verified the total and vesicle-derived miRNA expression profiles from plasma samples in healthy controls and patients with esophageal squamous cell carcinoma (ESCC). In the present study, four miRNA species miR-636, miR-7641, miR-28-3p, and miR-1246 that were differentially expressed in ESCC patients were chosen for further study. We first elucidated their essential function in ESCC progression and further explored their preliminary mechanism by identifying target proteins and involving signal pathways. Subsequently, the prognostic miRNA panels including miR-636, miR-7641, miR-1246, and miR-28-3p for ESCC diagnosis were constructed and validated using different cohort. Our results showed that the panel including the above four miRNAs derived from plasma EVs was most effective in distinguishing tumor patients from normal subjects, while integrated plasma EVs-derived miR-1246, miR-28-3p and total plasma miRNAs miR-636, miR-7641 showed the best capability in predicting lymph node metastasis. In summary, our studies revealed that plasma EVs-derived miRNAs could be emerged as promising biomarkers for ESCC diagnosis.

RNA sequencing reveals the implication of the circRNA-associated ceRNA network in oesophageal squamous cell carcinoma.

Circular RNAs (circRNAs) have attracted increasing attention in cancer research. However, there are few studies about the high-throughput sequencing for clinical cohorts focussing on the expression characteristics and regulatory networks of circRNAs in oesophageal squamous cell carcinoma (ESCC) until now. Present study aim to comprehensively recognize the functional and mechanistic patterns of circRNA through constructing a circRNA-related competing endogenous RNA (ceRNA) network in ESCC. Summarily, RNA high-throughput sequencing was adopted to assess the circRNA, miRNA and mRNA expression profiles in ESCC. Through bioinformatics methods, a circRNA-miRNA-mRNA coexpression network was constructed and hub genes was identified. Finally, cellular function experiments combined with bioinformatics analysis were conducted to verify the identified circRNA was involved in the progression of ESCC through ceRNA mechanism. In this study, we established a ceRNA regulatory network, including 5 circRNAs, 7 miRNAs and 197 target mRNAs, and 20 hub genes were screened and identified to exert important roles in the progression of ESCC. As a verification, hsa_circ_0002470 (circIFI6) was revealed to be highly expressed in ESCC and regulate the expression of hub genes by absorbing miR-497-5p and miR-195-5p through ceRNA mechanism. Our results further indicated that silencing of circIFI6 repressed proliferation and migration of ESCC cells, highlighting the tumour promotion effects of circIFI6 in ESCC. Collectively, our study contributes a new insight into the progression of ESCC from the perspective of the circRNA-miRNA-mRNA network, shedding light on the circRNA research in ESCC.

[Research progress of Helicobacter pylori vaccine].

Helicobacter pylori (Hp) is one of most common pathogens causing gastrointestinal disorder including gastric ulcer, duodenal ulcer and gastric cancer, etc. It has been verified as class I carcinogen by WHO. Nowadays, combination antibiotics and proton pump inhibitor are mainly used to erase Hp in clinical application. However, with the increased resistance of Hp, the vaccine against Hp might become the best strategy to eradicate Hp. Elements including urease, virulence factor, outer membrane protein, flagella, play an important role in Hp infection, colonization and reproduction. They have become potential candidate antigens in the development of Hp vaccine, as reported in previous studies. Presently, these antigens-centric vaccines have been tested in animal models. Therefore, this article reviews the studies on Hp vaccine with urease, virulence genes, outer membrane protein and flagella as their candidate antigens, in an attempt to provide insights for research in this regard.

The NR_109/FUBP1/c-Myc axis regulates TAM polarization and remodels the tumor microenvironment to promote cancer development.

BACKGROUND: Tumor-associated macrophages (TAMs) are a major component of the tumor microenvironment (TME) and exert an important role in tumor progression. Due to the heterogeneity and plasticity of TAMs, modulating the polarization states of TAMs is considered as a potential therapeutic strategy for tumors. Long noncoding RNAs (lncRNAs) have been implicated in various physiological and pathological processes, yet the underlying mechanism on how lncRNAs manipulate the polarization states of TAMs is still unclear and remains to be further investigated. METHODS: Microarray analyses were employed to characterize the lncRNA profile involved in THP-1-induced M0, M1 and M2-like macrophage. Among those differentially expressed lncRNAs, NR_109 was further studied, for its function in M2-like macrophage polarization and the effects of the condition medium or macrophages mediated by NR_109 on tumor proliferation, metastasis and TME remodeling both in vitro and in vivo. Moreover, we revealed how NR_109 interacted with far upstream element-binding protein 1 (FUBP1) to regulate the protein stability through hindering ubiquitination modification by competitively binding with JVT-1. Finally, we examined sections of tumor patients to probe the correlation among the expression of NR_109 and related proteins, showing the clinical significance of NR_109. RESULTS: We found that lncRNA NR_109 was highly expressed in M2-like macrophages. Knockdown NR_109 impeded IL-4 induced M2-like macrophage polarization and significantly reduced the activity of M2-like macrophages to support the proliferation and metastasis of tumor cells in vitro and in vivo. Mechanistically, NR_109 competed with JVT-1 to bind FUBP1 at its C-terminus domain, impeded the ubiquitin-mediated degradation of FUBP1, activated c-Myc transcription and thus promoted M2-like macrophages polarization. Meanwhile, as a transcription factor, c-Myc could bind to the promoter of NR_109 and enhance the transcription of NR_109. Clinically, high NR_109 expression was found in CD163+ TAMs from tumor tissues and was positively correlated with poor clinical stages of patients with gastric cancer and breast cancer. CONCLUSIONS: Our work revealed for the first time that NR_109 exerted a crucial role in regulating the phenotype-remodeling and function of M2-like macrophages via a NR_109/FUBP1/c-Myc positive feedback loop. Thus, NR_109 has great translational potentials in the diagnosis, prognosis and immunotherapy of cancer.

P-Hydroxylcinnamaldehyde induces tumor-associated macrophage polarization toward the M1 type by regulating the proteome and inhibits ESCC in vivo and in vitro.

P-Hydroxylcinnamaldehyde (CMSP) was firstly isolated from Chinese medicine Cochinchinnamomordica seed (CMS) by our team and has been verified to have growth-inhibiting abilities in malignant tumors including esophageal squamous cell carcinoma (ESCC). However, the detailed mechanism of its function is still unclear. Tumor-associated macrophages (TAMs) are an essential component of the tumor microenvironment (TME), playing important roles in tumor growth, metastasis, angiogenesis, and epithelial-mesenchymal transition (EMT). In the present study, we found that the percentage of M1-like macrophages was significantly increased in TME of ESCC cell derivedxenograft tumor model after CMSP treatment, while the ratios of other immune cells showed relatively low variation. To confirm these results, we further examined the effect of CMSP on macrophage polarization in vitro. The results revealed that CMSP also could induce phorbol-12-myristate-13-acetate (PMA)-induced M0 macrophages from THP-1 and mouse peritoneal macrophages toward the M1-like macrophages. Furthermore, CMSP could exert anti-tumor effect through TAMs in vitro co-culture model, in addition, the growth inhibition effect of CMSP was partly abolished in macrophage depletion model. To determine the potential pathway of CMSP induced polarization, we used quantitative proteomics (label-free) technology to explore the proteomic changes under CMSP treatment. The results revealed that immune-activating protein and M1 macrophage biomarkers were significantly increased after CMSP treatment. More importantly, CMSP stimulated pathways related to M1 macrophage polarization, such as the NF-κB signaling pathway and Toll-like receptor pathway, indicating that CMSP might induce M1-type macrophage polarization through these pathways. In conclusion, CMSP can regulate immune microenvironment in vivo and induce TAM polarization toward the M1 type by promoting proteomic changes, and exert anti-tumor effect through TAMs.

RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis.

Cellular senescence provides a protective barrier against tumorigenesis in precancerous or normal tissues upon distinct stressors. However, the detailed mechanisms by which tumor cells evade premature senescence to malignant progression remain largely elusive. Here we reported that RBM4 adversely impacted cellular senescence to favor glutamine-dependent survival of esophageal squamous cell carcinoma (ESCC) cells by dictating the activity of LKB1, a critical governor of cancer metabolism. The level of RBM4 was specifically elevated in ESCC compared to normal tissues, and RBM4 overexpression promoted the malignant phenotype. RBM4 contributed to overcome H-RAS- or doxorubicin-induced senescence, while its depletion caused P27-dependent senescence and proliferation arrest by activating LKB1-AMPK-mTOR cascade. Mechanistically, RBM4 competitively bound LKB1 to disrupt the LKB1/STRAD/MO25 heterotrimeric complex, subsequently recruiting the E3 ligase TRIM26 to LKB1, promoting LKB1 ubiquitination and degradation in nucleus. Therefore, such molecular process leads to bypassing senescence and sustaining cell proliferation through the activation of glutamine metabolism. Clinically, the ESCC patients with high RBM4 and low LKB1 have significantly worse overall survival than those with low RBM4 and high LKB1. The RBM4 high/LKB1 low expression confers increased sensitivity of ESCC cells to glutaminase inhibitor CB-839, providing a novel insight into mechanisms underlying the glutamine-dependency to improve the efficacy of glutamine inhibitors in ESCC therapeutics.

PRMT5 promotes ovarian cancer growth through enhancing Warburg effect by methylating ENO1.

Protein arginine methyltransferase 5 (PRMT5) is a major type II enzyme responsible for symmetric dimethylation of arginine (SDMA), and plays predominantly roles in human cancers, including in ovarian cancer. However, the exactly roles and underlying mechanisms of PRMT5 contributing to the progression of ovarian cancer mediated by reprogramming cell metabolism remain largely elusive. Here, we report that PRMT5 is highly expressed and correlates with poor survival in ovarian cancer. Knockdown or pharmaceutical inhibition of PRMT5 is sufficient to decrease glycolysis flux, attenuate tumor growth, and enhance the antitumor effect of Taxol. Mechanistically, we find that PRMT5 symmetrically dimethylates alpha-enolase (ENO1) at arginine 9 to promotes active ENO1 dimer formation, which increases glycolysis flux and accelerates tumor growth. Moreover, PRMT5 signals high glucose to increase the methylation modification of ENO1. Together, our data reveal a novel role of PRMT5 in promoting ovarian cancer growth by controlling glycolysis flux mediated by methylating ENO1, and highlights that PRMT5 may represent a promising therapeutic target for treating ovarian cancer.

Relationship between pathogenic microorganisms and the occurrence of esophageal carcinoma based on pathological type: a narrative review.

INTRODUCTION: Esophageal cancer (EC) is one of the most common malignant tumors of the upper gastrointestinal tract. The etiology of EC is complicated and increasing evidence has shown that microbial infection is closely related to the occurrence of various malignant tumors. Though many studies have been focused on this subject in recent years, the exact relationship between microbial infection and the occurrence of EC remains unclear. AREAS COVERED: In this review, we searched all eligible literature reports, summarized the most recent studies in this research field, and analyzed the pathogenic microorganisms associated with EC, providing the latest evidence and references for the prevention of pathogenic microorganism-related EC. EXPERT OPINION: In recent years, increasing evidence has shown that pathogenic microbial infections are closely associated with the development of EC. Therefore, it is necessary to describe in detail the relationship between microbial infection and EC and clarify its possible pathogenic mechanism, which will shed a light on clinical prevention and treatment of cancer caused by pathogenic microbial infection.

LncRNA SNHG5 Suppresses Cell Migration and Invasion of Human Lung Adenocarcinoma via Regulation of Epithelial-Mesenchymal Transition.

Long noncoding RNAs (lncRNAs) are gradually being annotated as important regulators of multiple cellular processes. The goal of our study was to investigate the effects of the lncRNA small nucleolar RNA host gene 5 (SNHG5) in lung adenocarcinoma (LAD) and its underlying mechanisms. The findings revealed a substantial drop in SNHG5 expression in LAD tissues, which correlated with clinical-pathological parameters. Transcriptome sequencing analysis demonstrated that the inhibitory effect of SNHG5 was associated with cell adhesion molecules. Moreover, the expression of SNHG5 was shown to be correlated with epithelial-mesenchymal transition (EMT) markers in western blots and immunofluorescence. SNHG5 also had significant effects of antimigration and anti-invasion on LAD cells in vitro. Furthermore, the migration and invasion of A549 cells were suppressed by overexpressed SNHG5 in the EMT progress induced by transforming growth factor ß1 (TGF-ß1), and this might be due to the inhibition of the expression of EMT-associated transcription factors involving Snail, SLUG, and ZEB1. In LAD tissues, the expression of SNHG5 exhibited a positive association with E-cadherin protein expression but a negative correlation with N-cadherin and vimentin, according to the results of quantitative real-time PCR (qRT-PCR). In summary, the current work demonstrated that the lncRNA SNHG5 might limit cell migration and invasion of LAD cancer via decreasing the EMT process, indicating that SNHG5 might be used as a target for LAD therapeutic methods.

Combination of size-exclusion chromatography and ion exchange adsorption for improving the proteomic analysis of plasma-derived extracellular vesicles.

Extracellular vesicles (EVs) are lipid membrane vesicles released by live cells that carry a variety of biomolecules, including nucleic acids, lipids, and proteins. Recently, proteins in plasma-derived EVs have emerged as novel biomarkers with essential functions in the diagnosis and prognosis of human diseases. However, the current methods of isolating EVs from plasma often lead to coisolated impurities in biological fluids. Therefore, before performing any research protocol, the process of extracting EVs from plasma for proteomic analysis must be optimized. In this study, two EV isolation strategies, size exclusion chromatography (SEC) and SEC combined with ion exchange adsorption (SEC + IEA), were compared in terms of the purity and quantity of protein in EVs. Our results demonstrated that, compared to single-step SEC, SEC combined with IEA could produce plasma-derived EVs with a higher purity by decreasing the abundance of lipoprotein. Additionally, with MS analysis, we demonstrated that the combination approach maintained the stability and improved the purity of EVs in many plasma samples. Furthermore, by combining SEC with IEA, more cancer-associated proteins were detected in the plasma of various cancer samples.

Perspectives from recent advances of Helicobacter pylori vaccines research.

BACKGROUND: Helicobacter pylori (H. pylori) infection is the main factor leading to some gastric diseases. Currently, H. pylori infection is primarily treated with antibiotics. However, with the widespread application of antibiotics, H. pylori resistance to antibiotics has also gradually increased year by year. Vaccines may be an alternative solution to clear H. pylori. AIMS: By reviewing the recent progress on H. pylori vaccines, we expected it to lead to more research efforts to accelerate breakthroughs in this field. MATERIALS & METHODS: We searched the research on H. pylori vaccine in recent years through PubMed®, and then classified and summarized these studies. RESULTS: The study of the pathogenic mechanism of H. pylori has led to the development of vaccines using some antigens, such as urease, catalase, and heat shock protein (Hsp). Based on these antigens, whole-cell, subunit, nucleic acid, vector, and H. pylori exosome vaccines have been tested. DISCUSSION: At present, researchers have developed many types of vaccines, such as whole cell vaccines, subunit vaccines, vector vaccines, etc. However, although some of these vaccines induced protective immunity in mouse models, only a few were able to move into human trials. We propose that mRNA vaccine may play an important role in preventing or treating H. pylori infection. The current study shows that we have developed various types of vaccines based on the virulence factors of H. pylori. However, only a few vaccines have entered human clinical trials. In order to improve the efficacy of vaccines, it is necessary to enhance T-cell immunity. CONCLUSION: We should fully understand the pathogenic mechanism of H. pylori and find its core antigen as a vaccine target.

Prognosis value of IL-6, IL-8, and IL-1ß in serum of patients with lung cancer: A fresh look at interleukins as a biomarker.

Interleukins are assumed to be closely related to the occurrence and development of human malignant tumors, while a few of them were commonly used as diagnostic markers in clinical cancer, including lung cancer. This study aimed to explore the value of serum interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and interleukin-8 (IL-8) combined with carcinoembryonic antigen (CEA) as biomarker panel for the diagnosis and metastasis prediction of lung cancer. IL-1ß, IL-6, IL-8, and CEA in serum were determined using electrochemiluminescence immunoassay (ECLIA) and flow cytometry, and the diagnostic value of each marker was analyzed using receiver operating characteristic (ROC) curves and logistic fitting regression. We found that the levels of serum IL-1ß, IL-6, and IL-8 showed no significant difference among squamous cell carcinoma, adenocarcinoma, and small cell carcinoma, while they were significantly higher in the lung cancer group or benign group than those in the healthy group. The levels of IL-8 and CEA were positively correlated with clinical stages respectively. Importantly, the panel of CEA + IL-6 + IL-8 has the highest efficacy for the diagnosis of lung cancer (AUC = 0.883) among all the detected panels, while the panel of IL-8 + CEA showed the most promising predictive value for the lymph node metastasis (AUC = 0.686) and distant metastasis of lung cancer (AUC = 0.793). In conclusion, IL-6 and IL-8 could be used as promising molecular biomarkers to diagnose and predict the metastasis of lung cancer independent of pathological types, improving the specificity and sensitivity of diagnosis for lung cancer when they were combined with CEA.