Biomarkers For Disease Prognosis Research Articles

Diagnostic and prognostic potential of the intra-tumoral microbiota profile in HPV-independent endocervical adenocarcinoma.

Microbial community dynamics have been involved in numerous diseases, including cancer. The diversity of intertumoral microbiota in human papillomavirus independent endocervical adenocarcinoma (HPVI ECA) is not well-characterized. Our objective is to delineate the intratumoral microbiota profile in HPVI ECA and investigate its potential influence on oncogenesis. We analyzed 45 HPVI ECA cases, comprising 36 gastric-type ECA (GEA) and 9 clear cell carcinomas (CCC). We compared the microbial composition within cancerous and adjacent noncancerous tissue samples using 5R-16S ribosomal DNA sequencing. Further, we investigated the correlation between specific microbes and clinical-pathological metrics as well as patient outcomes. Our findings demonstrate notable differences in the microbial spectra between cancerous and adjacent noncancerous tissues. Amongst HPVI ECA subtypes, GEAs exhibit more microbial variations compared to CCCs. Using the Random Forest algorithm, we identified two distinct microbial signatures that could act as predictive biomarkers for HPVI ECA and differentiate between GEA and CCC. Varied microbial abundances was related to clinical characteristics of HPVI ECA patients. In addition, high levels of Micrococcus and low levels of unknown genus75 from the Comamonadaceae family were associated with poorer outcomes in HPVI ECA patients. Similarly, an abundance of Microbacterium correlated with reduced overall survival (OS), and a high presence of Streptococcaceae family microbes was linked to reduced recurrence-free survival (RFS) in GEA patients. Intriguingly, a high abundance of Micrococcus was also associated with a worse OS in GEA patients. The study reveals distinct microbial signatures in HPVI ECA, which have potential as biomarkers for disease prognosis. The correlation between these tumor-associated microbiota features and clinicopathological characteristics underscores the possibility of microbiome-based interventions. Our research provides a foundation for more in-depth studies into the cervical microbiome's role in HPVI ECA.

Identification and experimental validation of a tumor-infiltrating lymphocytes-related long noncoding RNA signature for prognosis of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common aggressive malignant tumor of the urinary system. Given the heterogeneity of the tumor microenvironment, immunotherapy may not fully exert its role in the treatment of advanced patients. Long noncoding RNA (lncRNA) has been reported to be critically associated with the differentiation and maturation of tumor-infiltrating lymphocytes (TILs), which work against tumor cells. In this study, we identified 10 TIL-related lncRNAs (AL590094.1, LINC02027, LINC00460, AC147651.1, AC026401.3, LINC00944, LINC01615, AP000439.2, AL162586.1, and AC084876.1) by Pearson correlation, univariate Cox regression, Lasso regression, and multivariate Cox regression based on The Cancer Genome Atlas (TCGA) database. A risk score model was established based on these lncRNAs. Next, a nomogram was constructed to predict the overall survival. By employing differentially expressed genes (DEGs) between groups with high and low risk scores, gene ontology (GO) enrichment analysis was performed to identify the major biological processes (BP) related to immune DEGs. We analyzed the mutation data of the groups and demonstrated that SETD2 and BAP1 had the highest mutation frequency in the high-risk group. The "CIBERSORT" R package was used to detect the abundance of TILs in the groups. The expression of lymphocyte markers was compared. We also determined the expression of two lncRNAs (AC084876.1 and AC026401.3) and their relationship with lymphocyte markers in the kidney tissue of ccRCC patients and showed that there was a positive correlation between AC084876.1 and FoxP3. Proliferation, migration, and invasion of AC084876.1-downregulated ccRCC cell lines were inhibited, and the expression of PD-L1 and TGF-β secretion decreased. To our knowledge, this is the first bioinformatics study to establish a prognostic model for ccRCC using TIL-related lncRNAs. These lncRNAs were associated with T-cell activities and may serve as biomarkers of disease prognosis.

Extracellular Vesicles As Markers of Inflammation and Hypercoagulability during the First Month of Sars-COV-2 Infection in Outpatients and Hospitalized Patients

During SARS-CoV-2 infection, a severe hypercoagulability state is observed due to the stimulus of multiple mechanisms of hemostasis, such as intrinsic and extrinsic coagulation pathways, activation of platelets, endothelial cells, monocytes and neutrophils endothelial and impaired fibrinolysis. As a consequence, thrombotic complications are common in the course of COVID-19. Microvesicles (MVs) are intracellular transmitters that participate in pathological conditions, such as inflammatory and infectious processes, and are capable of triggering prothrombotic mechanisms. Since MVs release is potentially associated with COVID-19-induced coagulopathy, our aim was to identify the moment during the time course of the disease when the stimulus for MVs release occurs and whether this was associated with adverse outcomes. Therefore, we evaluate changes in MVs markers levels during the first month of SARS-CoV-2 infection in patients with severe disease (patients hospitalized in an intensive care unit - ICU) as compared to outpatients. We also evaluated the association between MVs markers and: acute phase inflammatory biomarkers (C-reactive protein, CRP), hypercoagulability (D-dimer) and death. Blood samples of patients were collected on three occasions: before the 10th day of symptoms (6th to 10th day), in the third week of symptoms (16th to 20th) and in the fourth week of symptoms (21st to 25th day) for the quantification of the following MVs markers by flow cytometry: CD41A (platelet activation), CD162 (PSGL-1; leukocyte-platelet interaction), CD31 (endothelium-platelet interaction) and CD142 (tissue factor). Statistical tests of ANOVA with repeated measures, Mann-Whitney and regression methods were used. The population studied was 85 patients, 65 outpatients and 20 ICU patients. Forty-three were men (51%), with a median age of 41 years old. The concentration of MVs expressing CD31+, CD41+, CD162+ and CD142+ were persistently elevated in patients who required ICU compared to outpatients at the 3 moments studied, except for the levels of MVs-CD31+ and MVs-CD142+ that were similar between ICU and outpatients in the fourth week of symptoms. However, despite the differences between the groups, there were no significant changes in the concentration of MVs during the course of the disease within the groups. In subgroup analysis, we observed that increases in the levels of MVs-CD162+ and MVs-CD142+ in the third week of symptoms were associated with the risk of death (P=0.02 and P=0.06, respectively). We also observed that before the 10th day of symptoms there was no correlation between MVs markers, CRP and D dimer levels. However, throughout the course of the disease the association between MVs, coagulability and inflammation was evident. In the third week of symptoms, D-dimer levels were correlated with MV-CD31+ (r=0.52; P<0.0001), MV-CD162+ (r=0.35, P=0.001), MV-CD41A+ (r=0.44, P<0.0001) and MV-CD142+ (r=0.47, P<0.0001). In the fourth week of symptoms, these correlations remained unchanged. CRP values from the third week of symptoms were correlated with MV-CD31+ (r=0.56, P=<0.0001), MV-CD162+ (r=0.48, P<0.0001), MV-CD41A+ (r= 0.41, P=0.0001), and MV-CD142+ (r=0.56, P<0.0001). In the fourth week of symptoms, these correlations remained unchanged. In conclusion, MVs that express antigens related to platelet activation, leukocyte-platelet interaction and endothelium-platelet interaction, as well as those related to tissue factor are released during the course of COVID-19 in patients with severe disease. After the 4th week of symptoms, the release of these MVs was associated with signs of inflammation and hypercoagulability. Additionally, MVs that express tissue factor and leukocyte-platelet interaction antigens were particularly high among non-survivors, suggesting that these MVs may serve as markers of the risk of death. Finally, these findings suggest the participation of innate immunity and tissue factor pathways in the prognosis of COVID-19, and point towards a possible role of MVs as biomarkers of disease prognosis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Mitochondrial Fatty Acid β-Oxidation Disorders: From Disease to Lipidomic Studies-A Critical Review.

Fatty acid oxidation disorders (FAODs) are inborn errors of metabolism (IEMs) caused by defects in the fatty acid (FA) mitochondrial β-oxidation. The most common FAODs are characterized by the accumulation of medium-chain FAs and long-chain (3-hydroxy) FAs (and their carnitine derivatives), respectively. These deregulations are associated with lipotoxicity which affects several organs and potentially leads to life-threatening complications and comorbidities. Changes in the lipidome have been associated with several diseases, including some IEMs. In FAODs, the alteration of acylcarnitines (CARs) and FA profiles have been reported in patients and animal models, but changes in polar and neutral lipid profile are still scarcely studied. In this review, we present the main findings on FA and CAR profile changes associated with FAOD pathogenesis, their correlation with oxidative damage, and the consequent disturbance of mitochondrial homeostasis. Moreover, alterations in polar and neutral lipid classes and lipid species identified so far and their possible role in FAODs are discussed. We highlight the need of mass-spectrometry-based lipidomic studies to understand (epi)lipidome remodelling in FAODs, thus allowing to elucidate the pathophysiology and the identification of possible biomarkers for disease prognosis and an evaluation of therapeutic efficacy.

Unravelling hub genes as potential therapeutic targets in lung cancer using integrated transcriptomic meta-analysis and in silico approach

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Smoking has been identified as the main contributing cause of the disease’s development. The study aimed to identify the key genes in small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), the two major types of LC. Meta-analysis was performed with two datasets GSE74706 and GSE149507 obtained from Gene Expression Omnibus (GEO). Both the datasets comprised samples from cancerous and adjacent non-cancerous tissues. Initially, differentially expressed genes (DEGs) were identified. To understand the underlying molecular mechanism of the identified genes, pathway enrichment, gene ontology (GO) and protein–protein interaction (PPI) analyses were done. A total of hub genes were identified which were subjected to mutation study analysis in LC patients using cBioPortal. These genes (i.e. AURKA, AURKB, KIF23, RACGAP1, KIF2C, KIF20A, CENPE, TPX2 and PRC1) have shown overexpression in LC patients and can be explored as potential candidates for prognostic biomarkers. TPX2 reported a maximum mutation of This was followed with high throughput screening and docking analysis to identify the potential drug candidates following competitive inhibition of the AURKA-TPX2 complex. Four compounds, CHEMBL431482, CHEMBL2263042, CHEMBL2385714, and CHEMBL1206617 were identified. The results signify that the selected 9 genes can be explored as biomarkers in disease prognosis and targeted therapy. Also, the identified 4 compounds can be further analyzed as promising therapeutic candidates. Communicated by Ramaswamy H. Sarma

EXTRACELLULAR VESICLES AS MARKERS OF INFLAMMATION AND HYPERCOAGULABILITY DURING THE FIRST MONTH OF SARS-COV-2 INFECTION IN OUTPATIENTS AND HOSPITALIZED PATIENTS

IntroductionDuring SARS-CoV-2 infection, a severe hypercoagulability state is observed due to the stimulus of multiple mechanisms of hemostasis, such as coagulation, activation of platelets, endothelial cells, monocytes and neutrophils and impaired fibrinolysis. As a consequence, thrombotic complications are common in the course of COVID-19. Microvesicles (MVs) are intracellular transmitters that participate in pathological conditions, such as inflammatory and infectious processes, and are capable of triggering prothrombotic mechanisms. Since MVs release is potentially associated with COVID-19-induced coagulopathy, our aim was to identify during the course of the disease when the stimulus for MVs release occurs and whether this was associated with adverse outcomes.ObjectiveWe evaluated changes in the levels of MVs markers during the first month of SARS-CoV-2 infection in patients (pts) with severe disease (hospitalized in an Intensive Care Unit ‒ ICU) as compared to outpatients. We also evaluated the association between MVs markers with: inflammatory biomarkers (C-reactive protein, CRP), hypercoagulability (D-dimer) and death.MethodsBlood samples were collected on three occasions: before the 10th day of symptoms, in the 3rd week of symptoms and in the 4th week of symptoms for the quantification of the following MVs markers by flow cytometry: CD41A (platelet activation), CD162 (PSGL-1; leukocyte-platelet interaction), CD31 (endothelium-platelet interaction) and CD142 (tissue factor). Statistical tests of ANOVA with repeated measures, Mann-Whitney and regression methods were used.ResultsThe population studied was 85 pts, being 25 from ICU. Mostly were men (51%), with a median age of 41 years. The concentration of MVs expressing CD31+, CD41+, CD162+ and CD142+ were persistently elevated in pts who required ICU compared to outpatients at the 3 moments studied, except for the levels of MVs-CD31+ and MVs-CD142+ that were similar between ICU and outpatients in the 4th week of symptoms. However, despite the differences between the groups, there were no significant changes in the levels of MVs during the course of the disease within the groups. In subgroup analysis, we observed that increases in the levels of MVs-CD162+ and MVs-CD142+ in the 3rd week of symptoms were associated with the risk of death (p=0.02 and p=0.06, respectively). We also observed that during the course of the disease an association between MVs, coagulability and inflammation was evident. In the 3rd week of symptoms, D-dimer levels were correlated with MV-CD31+ (r=0.52, p<0.0001), MV-CD162+ (r=0.35, p=0.001), MV-CD41A+ (r=0.44, p<0.0001) and MV-CD142+ (r=0.47, p<0.0001) and CRP values were correlated with MV-CD31+ (r=0.56, p=<0.0001), MV-CD162+ (r=0.48, p<0.0001), MV-CD41A+ (r= 0.41, p=0.0001), and MV-CD142+ (r=0.56, p<0.0001). By the 4th week of symptoms, both D-dimers and CRP correlations with the above MVs remained unchanged.ConclusionTo conclude, MVs that express antigens related to platelet activation, leukocyte-platelet interaction and endothelium-platelet interaction, as well as those related to tissue factor are released during the course of COVID-19 in pts with severe disease. After the 4th week of symptoms, the release of these MVs was associated with signs of inflammation and hypercoagulability. Additionally, MVs that express tissue factor and leukocyte-platelet interaction antigens were particularly high among non-survivors, suggesting that these MVs may serve as markers of the risk of death. Finally, these findings suggest the participation of innate immunity and tissue factor pathways in the prognosis of COVID-19, and point towards a possible role of MVs as biomarkers of disease prognosis.

Testing microbiome associations with survival times at both the community and individual taxon levels.

Finding microbiome associations with possibly censored survival times is an important problem, especially as specific taxa could serve as biomarkers for disease prognosis or as targets for therapeutic interventions. The two existing methods for survival outcomes, MiRKAT-S and OMiSA, are restricted to testing associations at the community level and do not provide results at the individual taxon level. An ad hoc approach testing each taxon with a survival outcome using the Cox proportional hazard model may not perform well in the microbiome setting with sparse count data and small sample sizes. We have previously developed the linear decomposition model (LDM) for testing continuous or discrete outcomes that unifies community-level and taxon-level tests into one framework. Here we extend the LDM to test survival outcomes. We propose to use the Martingale residuals or the deviance residuals obtained from the Cox model as continuous covariates in the LDM. We further construct tests that combine the results of analyzing each set of residuals separately. Finally, we extend PERMANOVA, the most commonly used distance-based method for testing community-level hypotheses, to handle survival outcomes in a similar manner. Using simulated data, we showed that the LDM-based tests preserved the false discovery rate for testing individual taxa and had good sensitivity. The LDM-based community-level tests and PERMANOVA-based tests had comparable or better power than MiRKAT-S and OMiSA. An analysis of data on the association of the gut microbiome and the time to acute graft-versus-host disease revealed several dozen associated taxa that would not have been achievable by any community-level test, as well as improved community-level tests by the LDM and PERMANOVA over those obtained using MiRKAT-S and OMiSA. Unlike existing methods, our new methods are capable of discovering individual taxa that are associated with survival times, which could be of important use in clinical settings.

Long non-coding RNA mediated drug resistance in breast cancer.

Breast cancer is one of the most prevalent cancers in women and a leading cause of mortality. As per the GLOBCAN report of 2021, breast cancer has surpassed lung cancer which until recently was the most commonly diagnosed cancer. Despite significant efforts to improve early detection and therapeutic efficacy of breast cancer, the frequent emergence of drug resistance remains the predominant basis for the poor prognosis of cancer patients harboring various malignancies. Long non-coding RNA (lncRNAs) are known to affect a variety of components of genome function, including epigenetics, gene transcription, splicing, translation, as well as many central biological processes like cell cycle progression, cell differentiation, development, and pluripotency. LncRNAs are dysregulated in various malignancies and interact with a multitude of RNAs and proteins to impact drug resistance. LncRNAs regulate chemoresistance in cancer by employing an assortment of molecular mechanisms including multidrug efflux, suppression of apoptosis, DNA damage response, epigenetic alterations, as well as functioning as competitive endogenous RNA. When combined with other regulatory mechanisms, these pathways form a complex orchestration of signaling that ultimately lead to chemoresistance. The current review delves into the role of lncRNAs in inducing drug resistance to conventional therapeutic anti-cancer drugs used for the treatment of breast cancer. We propose that lncRNAs that provoke drug resistance could be used to develop new targeted and tailored therapeutics providing a novel approach to introduce promising personalized treatment modalities to overcome chemoresistance in breast cancer patients. Hence, lncRNAs that drive anticancer drug resistance can be potentially explored as biomarkers of disease prognosis and may provide unique opportunities to circumvent chemoresistance in breast cancer patients.

Serum superoxide dismutase level is a potential biomarker of disease prognosis in patients with hemorrhagic fever with renal syndrome caused by the Hantaan virus

BackgroundHemorrhagic fever with renal syndrome (HFRS) is a disease with increased systemic inflammation and a high fatality rate. Oxidative stress is crucial for inflammation in the pathogeneses of various diseases. We aimed to identify biomarkers of oxidative stress that may assess the severity and disease outcomes of patients with HFRS.MethodsBetween January 2015 and September 2018, we analyzed a retrospective cohort of 149 HFRS patients and 30 healthy individuals. Serum levels of SOD were measured using an ELISA commercial kit, and survival analysis was carried out using the Kaplan–Meier method.ResultsPatients with HFRS had significantly lower serum SOD levels compared with healthy controls (108.40 ± 2.47 U/mL vs 164.23 ± 3.82 U/mL, P < 0.01). SOD levels in patients were lower at acute than at convalescent stage (108.40 ± 2.47 U/mL vs 138.27 ± 2.87 U/mL, P < 0.01), and in severe and critical patients than in moderate and mild patients (89.63 ± 2.38 U/mL vs 122.53 ± 3.18 U/mL, P < 0.01). A serum level of SOD < 88.6 U/mL at admission was associated with a significant increase in mortality risk in HFRS patients.ConclusionOur results indicate that serum levels of SOD measured at admission can be used to assess disease severity and assign patients into high- and low-risk groups. SOD can be considered a novel biomarker of severity and outcomes in patients with HFRS.

Proteomic Identification of a Gastric Tumor ECM Signature Associated With Cancer Progression.

The extracellular matrix (ECM) plays an undisputable role in tissue homeostasis and its deregulation leads to altered mechanical and biochemical cues that impact cancer development and progression. Herein, we undertook a novel approach to address the role of gastric ECM in tumorigenesis, which remained largely unexplored. By combining decellularization techniques with a high-throughput quantitative proteomics approach, we have performed an extensive characterization of human gastric mucosa, uncovering its composition and distribution among tumor, normal adjacent and normal distant mucosa. Our results revealed a common ECM signature composed of 142 proteins and indicated that gastric carcinogenesis encompasses ECM remodeling through alterations in the abundance of 24 components, mainly basement membrane proteins. Indeed, we could only identify one de novo tumor-specific protein, the collagen alpha-1(X) chain (COL10A1). Functional analysis of the data demonstrated that gastric ECM remodeling favors tumor progression by activating ECM receptors and cellular processes involved in angiogenesis and cell-extrinsic metabolic regulation. By analyzing mRNA expression in an independent GC cohort available at the TGCA, we validated the expression profile of 12 differentially expressed ECM proteins. Importantly, the expression of COL1A2, LOX and LTBP2 significantly correlated with high tumor stage, with LOX and LTBP2 further impacting patient overall survival. These findings contribute for a better understanding of GC biology and highlight the role of core ECM components in gastric carcinogenesis and their clinical relevance as biomarkers of disease prognosis.

MicroRNA548ac expression\xa0level in relation to BDCAF scored Beh\xe7et\u2019s disease\xa0activity and history of treatment response

BackgroundBehçet’s disease gives a challenge to be diagnosed and followed up due to lack of specific biomarkers. MicroRNAs showed relations to different disease states including immunological and inflammatory illnesses. In this study, we are estimating microRNA548ac levels for the first time to be tested in the disease to see if there is a link to disease activity and if microRNA548ac can be used as a biomarker for activity or remission and prognosis of Behçet’s disease. MicroRNA548ac has been shown to have a role in autoimmunity and some inflammatory conditions. Blood samples were taken from patients to measure white blood cells expression of microRNA548ac, and compared to its expression in healthy subjects, disease activity was assessed by usage of Behçet’s Disease Current Activity Form (BDCAF).ResultsMicroRNA548ac expression decreased but not significantly with increased Behçet’s disease activity, and expression was having a significant positive correlation with increased treatment response history.ConclusionsMicroRNA548ac appeared not to be related to disease activity which needs confirmation in further studies, but it may predict response to treatment so that patients having higher expression of microRNA548ac may have a better response to treatment. Here, microRNA548ac could be used as a disease biomarker for disease prognosis.

Role of miRNA-145, 148, and 185 and Stem Cells in Prostate Cancer.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a role in cancer linked to the regulation of important cellular processes and pathways involving tumorigenesis, cell proliferation, differentiation, and apoptosis. A lot of human miRNA sequences have been identified which are linked to cancer pathogenesis. MicroRNAs, in prostate cancer (PC), play a relevant role as biomarkers, show a specific profile, and have been used as therapeutic targets. Prostate cancer (PC) is the most frequently diagnosed cancer in men. Clinical diagnoses among the gold standards for PC diagnosis and monitoring are prostate-specific antigen (PSA) testing, digital rectal examination, and prostate needle biopsies. PSA screening still has a large grey area of patients, which leads to overdiagnosis. Therefore, new biomarkers are needed to improve existing diagnostic tools. The miRNA expression profiles from tumour versus normal tissues are helpful and exhibit significant differences not only between cancerous and non-cancerous tissues, but also between different cancer types and subtypes. In this review, we focus on the role of miRNAs-145, 148, and 185 and their correlation with stem cells in prostate cancer pathogenesis. MiR-145, by modulating multiple oncogenes, regulates different cellular processes in PC, which are involved in the transition from localised to metastatic disease. MiR-148 is downregulated in high-grade tumours, suggesting that the miR-148-3 family might act as tumour suppressors in PC as a potential biomarker for detecting this disease. MiR-185 regulation is still unclear in being able to regulate tumour processes in PC. Nevertheless, other authors confirm the role of this miRNA as a tumour suppressor, suggesting its potential use as a suitable biomarker in disease prognosis. These three miRNAs are all involved in the regulation of prostate cancer stem cell behaviour (PCSCs). Within this contest, PCSCs are often involved in the onset of chemo-resistance in PC, therefore strategies for targeting this subset of cells are strongly required to control the disease. Hence, the relationship between these two players is interesting and important in prostate cancer pathogenesis and in PCSC stemness regulation, in the attempt to pave the way for novel therapeutic targets in prostate cancer.

Serum superoxide dismutase level is a potential biomarker of disease prognosis in patients with HEV-induced liver failure

BackgroundViral hepatitis E clinically ranges from self-limiting hepatitis to lethal liver failure. Oxidative stress has been shown to mediate hepatic inflammation during HBV-induced liver failure. We investigated whether a biomarker of oxidative stress may be helpful in assessing severity and disease outcomes of patients with HEV-induced liver failure.MethodsClinical data were obtained from patients with HEV-induced acute viral hepatitis (AVH, n = 30), acute liver failure (ALF, n = 17), and acute-on-chronic liver failure (ACLF, n = 36), as well as from healthy controls (HC, n = 30). The SOD and HMGB1 levels were measured in serum by ELISA. HL-7702 cells were cultured and stimulated by serum from HEV-infected patients or by HMGB1; oxidative status was investigated by CellROX and apoptosis was investigated by flow cytometry.ResultsPatients with HEV-induced liver failure (including ALF and ACLF) showed increased SOD levels compared with HEV-AVH patients and healthy controls. SOD levels > 400 U/mL were associated with a significantly higher risk of mortality in HEV-ALF and HEV-ACLF patients. Serum from HEV-infected patients led to ROS accumulation, HMGB1 secretion, and apoptosis in HL-7702 cells. Antioxidant treatment successfully inhibited HEV-induced HMGB1 secretion, and HMGB1 promoted apoptosis in HL-7702 cells.ConclusionHEV increased oxidative stress in the pathogenesis of HEV-induced hepatic diseases. Early testing of serum SOD may serve as a predictor of both HEV-ALF and HEV-ACLF outcomes. Moreover, development of strategies for modulating oxidative stress might be a potential target for treating HEV-induced liver failure patients.

A comprehensive review of IL-26 to pave a new way for a profound understanding of the pathobiology of cancer, inflammatory diseases and infections.

Cytokines are considered vital mediators of the immune system. Down- or upregulation of these mediators is linked to several inflammatory and pathologic situations. IL-26 is referred to as an identified member of the IL-10 family and IL-20subfamily. Due to having a unique cationic structure, IL-26 exerts diverse functions in several diseases. Since IL-26 is mainly secreted from Th17, it is primarily considered a pro-inflammatory cytokine. Upon binding to its receptor complex (IL-10R1/IL-20R2), IL-26 activates multiple signalling mediators, especially STAT1/STAT3. In cancer, IL-26 induces IL-22-producing cells, which consequently decrease cytotoxic T-cell functions and promote tumour growth through activating anti-apoptotic proteins. In hypersensitivity conditions such as rheumatoid arthritis, multiple sclerosis, psoriasis and allergic disease, this cytokine functions primarily as the disease-promoting mediator and might be considered a biomarker for disease prognosis. Although IL-26 exerts antimicrobial function in infections such as hepatitis, tuberculosis and leprosy, it has also been shown that IL-26might be involved in the pathogenesis and exacerbation of sepsis. Besides, the involvement of IL-26has been confirmed in other conditions, including graft-versus-host disease and chronic obstructive pulmonary disease. Therefore, due to the multifarious function of this cytokine, it is proposed that the underlying mechanism regarding IL-26 function should be elucidated. Collectively, it is hoped that the examination of IL-26 in several contexts might be promising in predicting disease prognosis and might introduce novel approaches in the treatment of various diseases.

Expression levels and clinical values of miR-92b-3p in breast cancer

BackgroundmiR-92b is a carcinogenic miRNA that has great potential as a biomarker for disease prognosis, diagnosis, and treatment in the clinic. It is of great significance to analyse the relationship between miR-92b and the clinicopathological characteristics of cancer patients. This paper aimed to investigate the expression levels and clinical values of miR-92b-3p in breast cancer (BC).MethodsAltogether, 112 female BC patients who were treated in our hospital were included as a study group, and 108 healthy women who came to our hospital for physical examinations were included as a control group. miR-92b-3p expression in the serum of subjects in both groups was detected by fluorescence quantitative PCR (RT-PCR) to analyse the correlation of this miRNA with the patients’ pathological features and prognoses. The diagnostic value of miR-92b-3p expression for BC was analysed by plotting a receiver operating characteristic (ROC) curve.ResultsmiR-92b-3p expression was remarkably higher in the study group (P < 0.05), and its area under the curve (AUC) for detecting BC was 0.88. The expression was correlated with the tumour size, degree of differentiation, TNM staging, and lymphatic metastasis (P < 0.05). miR-92b-3p was significantly positively correlated with the TNM staging (r = 0.40, P < 0.05), was significantly negatively correlated with the degree of differentiation of the breast cancer cells (r = − 0.35, P < 0.05), and was significantly positively correlated with the expression of carbohydrate antigen 125 (CA125) (r = 0.39, P < 0.05). The overall survival rate (OSR) of the 99 patients who had follow-up was 73.74%. The survival status was remarkably better in the low expression group (P < 0.05). miR-92b-3p expression was remarkably higher in the death group (P < 0.05). The AUC of miR-92b-3p alone in the death and survival groups was 0.76.ConclusionmiR-92b-3p expression obviously rises in the serum of BC patients and is closely related to the clinical staging, degree of differentiation, and CA125 in BC, so the detection of this miRNA is of great significance to the diagnosis and prognostic evaluation of BC. This miRNA can be used as a potential biomarker for the diagnosis and prognosis of the disease.

Non-muscle invasive bladder cancer tissues have increased base excision repair capacity

The molecular mechanisms underlying the development and progression of bladder cancer (BC) are complex and have not been fully elucidated. Alterations in base excision repair (BER) capacity, one of several DNA repair mechanisms assigned to preserving genome integrity, have been reported to influence cancer susceptibility, recurrence, and progression, as well as responses to chemotherapy and radiotherapy. We report herein that non-muscle invasive BC (NMIBC) tissues exhibit increased uracil incision, abasic endonuclease and gap-filling activities, as well as total BER capacity in comparison to normal bladder tissue from the same patient (p < 0.05). No significant difference was detected in 8-oxoG incision activity between cancer and normal tissues. NMIBC tissues have elevated protein levels of uracil DNA glycosylase, 8-oxoguanine DNA glycosylase, AP endonuclease 1 and DNA polymerase β protein. Moreover, the fold increase in total BER and the individual BER enzyme activities were greater in high-grade tissues than in low-grade NMIBC tissues. These findings suggest that enhanced BER activity may play a role in the etiology of NMIBC and that BER proteins could serve as biomarkers in disease prognosis, progression or response to genotoxic therapeutics, such as Bacillus Calmette–Guérin.

Dynamic changes of lipid profile in severe hypertriglyceridemia-induced acute pancreatitis patients under double filtration plasmapheresis: a retrospective observational study

BackgroundTo investigate the dynamic change of lipid profile under double filtration plasmapheresis (DFPP) in severe hypertriglyceridemia-induced acute pancreatitis (sHTGP) patients and ascertain the association between these changes and the clinical prognosis.MethodssHTGP patients admitted within 72 h after disease onset were included, and all the patients received DFPP within 24 h after admission. Lipid profile were detected on admission, consecutive 4 days after DFPP and at discharge.ResultsThere were 47 sHTGP patients enrolled in this study. At admission, all the parameters of lipid profile changed significantly except for low density lipoprotein. In the first day after DFPP, the serum level of TG, cholesterol and very low density lipoprotein declined significantly, while the high-density lipoprotein (HDL) as well as apoprotein A1 elevated obviously (P < 0.05). TG maintained the downward trend in the following three days and the other parameters kept steady. Linear regression analysis showed that HDL was negatively correlated with the duration of hospitalization among three adjusted models (P = 0.043, P = 0.029, P = 0.025 respectively).ConclusionThere was distinct fluctuation of the lipid profile upon the burst of sHTGP and the parameters changed significantly in the first day after DFPP. Among these parameters, HDL may serve as a biomarker for disease prognosis in patients with sHTGP.

Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint.

Growth/differentiation factor-15 (GDF-15), also named macrophage inhibitory cytokine-1, is a divergent member of the transforming growth factor β superfamily. While physiological expression is barely detectable in most somatic tissues in humans, GDF-15 is abundant in placenta. Elsewhere, GDF-15 is often induced under stress conditions, seemingly to maintain cell and tissue homeostasis; however, a moderate increase in GDF-15 blood levels is observed with age. Highly elevated GDF-15 levels are mostly linked to pathological conditions including inflammation, myocardial ischemia, and notably cancer. GDF-15 has thus been widely explored as a biomarker for disease prognosis. Mechanistically, induction of anorexia via the brainstem-restricted GDF-15 receptor GFRAL (glial cell-derived neurotrophic factor [GDNF] family receptor α-like) is well-documented. GDF-15 and GFRAL have thus become attractive targets for metabolic intervention. Still, several GDF-15 mediated effects (including its physiological role in pregnancy) are difficult to explain via the described pathway. Hence, there is a clear need to better understand non-metabolic effects of GDF-15. With particular emphasis on its immunomodulatory potential this review discusses the roles of GDF-15 in pregnancy and in pathological conditions including myocardial infarction, autoimmune disease, and specifically cancer. Importantly, the strong predictive value of GDF-15 as biomarker may plausibly be linked to its immune-regulatory function. The described associations and mechanistic data support the hypothesis that GDF-15 acts as immune checkpoint and is thus an emerging target for cancer immunotherapy.

Integrative analysis of highly mutated genes in hepatitis B virus-related hepatic carcinoma.

Gene mutation is responsible for the development of hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection; however, the characteristics and associated biological functions of highly mutated genes, in which the mutation frequencies are at least 5% in HCC patients with HBV infection, are not clearly evaluated. In the study, we analyzed the information regarding somatic mutation obtained by whole‐exome sequencing in 280 HBV‐related HCC tissues from public databases and published studies. Via integrative analysis, 78 genes, including TP53, TTN, MUC16, CTNNB1, and PCLO were summarized as highly mutated genes, and some of these mutated genes were further identified as cancer driver genes. Besides, we discovered that the highly mutated genes were enriched with various biological functions and pathways. The expression of many of highly mutated genes was found to be significantly altered in HBV‐related HCC, and several highly mutated genes were related to a variety of clinical factors and associated with the poor survival of the disease. Taken together, these results could enrich our understanding of highly mutated genes and their relationships with HBV‐related HCC. Some of the identified highly mutated genes might be used as novel biomarkers of disease prognosis, or as molecular targets for the treatment of HCC with HBV infection.

Prognostic Value of MicroRNAs in Stage II Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis to identify and underline multiple microRNAs (miRNAs) as biomarkers of disease prognosis in stage II colorectal cancer (CRC) patients. This systematic review and meta-analysis study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The required articles were collected from online bibliographic databases from January 2011 to November 2019 with multiple permutation keywords. Quantitative data synthesis was based on a meta-analysis with pooled data to observe and analyse the outcome measures and effect estimates by using the random effect model. The subgroup analysis was performed from demographic characteristics and the available data. Eighteen articles were included in this study, 16 of which were incorporated for meta-analysis to examine the stage II CRC prognosis with up- and downregulated miRNA expressions. The pooled hazard ratio (HR) for death in stage II CRC patients was 1.90 (95% confidence interval 1.63-2.211), with a significant p value. A subgroup analysis based on up- or downregulated miRNA expression individually and any deregulated miRNA was also associated with a worse prognosis. The subgroup analysis included parameters such as age, gender, stage II and III combined patients' survival and the repetitive miRNAs (miR21, miR215, miR143-5p, miR106a and miR145) individually. MicroRNAs play a significant role in determining prognosis in stage II CRC patients, with upregulation of miR21, miR215, miR143-5p and miR106a, in particular, portending a worse prognosis. These miRNAs could be considered for further evaluation as biomarkers of prognosis and to guide the decision to administer adjuvant chemotherapy.