Potential Biomarkers In Patients Research Articles

Serological Antibodies against Kidney, Liver, and Spleen Membrane Antigens as Potential Biomarkers in Patients with Immune Disorders.

Immune disorders arise from complex genetic and environmental factors, which lead to dysregulation at the cellular and inflammatory levels and cause tissue damage. Recent research highlights the crucial role of reactive antibodies in autoimmune diseases and graft rejection, but their complex determination poses challenges for clinical use. Therefore, our study aimed to ascertain whether the presence of reactive antibodies against membrane antigens in tissues from both animal models and humans could serve as biomarkers in patients with autoimmune disorders. To address this issue, we examined the binding profile of serological antibodies against a diverse panel of cell membranes from the spleen, liver, and kidney tissues of monkeys, rats, and humans. After developing the cell membrane microarrays, human sera were immunologically assayed. The study was first conducted on sera from two groups, healthy subjects and patients with inflammatory and autoimmune disorders, and then optimized for kidney transplant patient sera. A significant increase in antibody reactivity against specific monkey kidney and spleen membranes was observed in the serum of patients with lupus nephritis, while kidney transplant patients showed a significant enhancement against human tissues and human embryonic kidney 293 cells. These results show the potential importance for clinical and basic research purposes of studying the presence of specific IgG against membrane antigens in patients' serum as potential biomarkers of immune disorders. However, it is important to note that these results need to be verified in further studies with a larger sample size to confirm their relevance.

Serum afamin and its implications in adult growth hormone deficiency: a prospective GH-withdrawal study.

Adult growth hormone deficiency (AGHD) is associated with a high prevalence of metabolic syndrome (MS), which contributes to the unfavorable cardiovascular risk profile in these patients. Insulin like growth factor-1 (IGF-1) is a widely used biomarker, however it does not always reflect the cardiometabolic risk and has a poor relationship with clinical efficacy endpoints. Consequently, there is an unmet need for biomarkers to monitor responses to GH-replacement. Afamin is a hormone-like glycoprotein, expressed in the liver. Higher afamin levels are strongly associated with MS and insulin resistance (IR). Although both MS and IR are very common in AGHD, afamin has not been investigated in these patients. To investigate afamin as a potential biomarker in patients with AGHD. Participants included 20 AGHD patients (11 GH-substituted and 9 GH-unsubstituted) and 37 healthy controls. Subjects underwent routine laboratory examinations, anthropometric measurements, body composition analysis using multi-frequency bioelectrical impedance analysis (InBody720) and measurement of serum afamin concentrations. In GH-substituted subjects, GH-substitution was withdrawn for 2 months. Measurements were carried out right before GH-withdrawal, at the end of the 2-month withdrawal period, and 1 month after reinstituting GH-replacement therapy (GHRT). GH-unsubstituted patients demonstrated higher afamin levels compared to controls (p=0.03). Afamin positively correlated with skeletal muscle mass, bone mineral content, total body water, extracellular- and intracellular water content, insulin (all, p<0.01), HOMA-IR (p=0.01) and C-peptide (p=0.03) levels in AGHD but not in healthy controls. In GH-substituted patients 2-month of GH-withdrawal caused significant changes in body composition, including decreased fat-free mass, skeletal muscle mass, total body water, and intracellular water content (all, p<0.01); but these changes almost fully recovered 1 month after reinstituting GHRT. Unexpectedly, afamin levels decreased after GH-withdrawal (p=0.03) and increased with reinstitution (p<0.01). Changes of afamin levels during GH-withdrawal positively correlated with changes of HOMA-IR (r=0.80; p<0.01) and changes of insulin (r=0.71; p=0.02). Higher afamin levels in unsubstituted AGHD patients might indicate severe metabolic dysregulation. Significant changes accompanying GH-withdrawal and reinstitution, along with strong correlations with measures of IR, suggest that afamin could be a promising biomarker to monitor GHRT-associated changes of insulin sensitivity.

The distribution of the extrachromosomal DNA molecules in early lung cancer.

Lung cancer (LC) is a highly lethal cancer worldwide. Research on the distribution and nature of extrachromosomal DNA molecules (EcDNAm) in early LC is scarce. In this study, after removing linear DNA and mitochondrial circular DNA, EcDNAm were extracted from two paired LC tissue samples and amplified using rolling circle amplification. High throughput extrachromosomal DNA (EcDNA) or RNA sequencing and bioinformatics analysis were subsequently utilized to explore the distribution and nature of the EcDNAm. Additionally, to elucidate the role of oncogenes with large EcDNAm sizes, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed. The RNA sequencing results revealed significant differences in certain genes between tumors and corresponding normal samples. At the same time, slight distinctions were observed between relapsed and non-relapsed tumor samples. The nature of the EcDNAm was compared between LC samples and matched normal samples. There was a tendency for the number of EcDNAm with longer size (EcDNA) and its containing driver oncogenes to be higher in cancer samples. Enrichment analysis of the cancer samples revealed enrichment in biological processes, such as positive regulation of protein localization, axon development, and in-utero embryonic development. This study highlights the universal distribution and characteristics of EcDNAm in early LC. Moreover, our work fills the investigation of the EcDNAm gap and future studies should focus on the application of EcDNA as a potential biomarker in patients with early LC.

GSDMB: A novel, independent prognostic marker and potential new therapeutic target in clear cell renal cell carcinoma.

Gasdermin (GSDM) family members are involved in numerous biological processes, including pyroptosis, as well as in the initiation and progression of various types of cancer. However, the specific role of GSDM genes in clear cell renal cell carcinoma (ccRCC) has yet to be fully clarified. The present study investigated the differential expression and genetic alterations GSDM genes, their effects on prognosis and immune modulation, and their functional enrichment in ccRCC. Several bioinformatics databases were used, including UALCAN, The Cancer Genome Atlas, Gene Expression Profiling Interactive Analysis, Metascape, Tumor Immune Estimation Resource, GSCALite and cBioPortal. The results revealed that the expression levels of GSDMA, GSDMB, GSDMC and GSDMD were significantly upregulated in cancer tissues compared with those in paracancerous tissues in patients with ccRCC, whereas the expression of DFNB59 exhibited the opposite trend. The results were experimentally validated in patients with ccRCC, and it was confirmed that the expression levels of GSDMA, GSDMB, GSDMC, GSDMD and GSDME (DFNA5) were significantly enhanced, whereas (PJVK, DFNB59) expression was reduced. In addition, elevated GSDMB, GSDMD and DFNA5 expression levels were clearly associated with worse pathological characteristics of ccRCC, including a high pathological stage and high tumor grade. Furthermore, the high expression levels of GSDMB, GSDMC, GSDMD, DFNA5 and PJVK were shown to be associated with worse overall survival (OS) and progression-free interval in patients with ccRCC. Both univariate and multivariate analyses indicated that the expression of GSDMB was independently associated with the OS of patients with ccRCC. Additionally, a high mutation rate of GSDM genes (33%) was observed in patients with ccRCC, and GSDM gene mutations were also significantly associated with a poor OS in patients with ccRCC. Significant associations between GSDM genes and ccRCC immunoprofiling and drug sensitivity were also determined. In conclusion, the findings of the present study indicated that GSDMB, GSDMD and DFNA5 may be considered promising therapeutic agents and potential biomarkers for patients with ccRCC. Furthermore, GSDMB could act as an independent predictor for the OS of patients with ccRCC.

Second-line treatment of PD-1 and CTLA-4 blockade combined with liposomal irinotecan plus leucovorin and fluorouracil for advanced cholangiocarcinoma: study protocol of a single-arm, prospective phase II trial

Background: Cholangiocarcinoma is a kind of malignant tumor that originates in the epithelium of the biliary tract. Although there are several options for second-line treatment for patients without specific genetic mutations, the overall treatment efficacy is disappointing. Second-line treatment which is composed of liposomal irinotecan plus fluorouracil and leucovorin significantly improved the treatment efficacy for advanced biliary tract cancer and extended patient survival. This study aims to evaluate the efficacy and safety of the combination of cadonilimab with liposomal irinotecan plus fluorouracil and leucovorin for advanced biliary tract cancer. Objectives: The primary objective of this study is to determine the objective response rate. The second objectives of this study are overall survival, progression-free survival, disease control rate, and adverse event incidence rate. Design: The study is a single-arm, prospective phase II clinical trial. In all, 51 patients who are diagnosed with locally advanced or metastatic bile tract cancer will be enrolled. Methods and analysis: Eligible participants will receive cadonilimab at a dosage of 6 mg/kg on day 1 of each 21-day cycle combined with intravenous liposomal irinotecan at a dosage of 70 mg/m2 for 90 min on day 1 plus leucovorin at a dosage of 400 mg/m2 for 30 min on day 1 and fluorouracil at a dosage of 400 mg/m2 for 46 h every 2 weeks. Discussion: Previous studies have suggested that there is a synergistic effect between the two treatment modalities. However, the potential of cadonilimab in bile tract cancer has not been explored. Hence, this trial is the first to investigate its efficacy and toxicity. In addition, the trial is also willing to explore potential biomarkers in patients with locally advanced and metastatic bile tract cancer. Trial registration: This study was registered on ClinicalTrials.gov with NCT06438822. Ethics: This study protocol and amendments have been approved by the Ethics Committee of West China Hospital (2024(791)).

The gut microbe-derived metabolite trimethylamine N-oxide in patients with systemic lupus erythematosus

Background/Aim: Both human and animal studies suggest that the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) is strongly associated with several autoimmune diseases including systemic lupus erythematosus (SLE) and correlates to disease severity. The study aimed to investigate the diagnostic and prognostic validity of TMAO as a potential biomarker in patients with SLE, particularly focusing on lupus nephritis patients and its relation to disease activity. Methods: A total of 90 patients were included and assigned into either: group I (SLE without nephritis (NN)), group II (lupus nephritis (LN)) and group III (healthy controls). Serum TMAO levels were compared between the study groups and correlated to the clinical, laboratory and histopathological criteria. Results: Unpredictably, TMAO levels were significantly higher in healthy controls compared to the total SLE population (p = 0.003), to LN and NN groups individually (p = 0.01). TMAO levels did not significantly vary be-tween (NN) and (LN) patients and only correlated to anti-dsDNA titres (p = 0.02) and red blood cells count (p = 0.02) among LN patients. Conclusion: Contrary to previous studies, TMAO levels were found to be higher in healthy controls. A possible confounding effect of the dietary pat-tern and ingested drugs on the gut microbiome limits the utility of TMAO as a potential marker in different diseases.

RNA Sequencing and Bioinformatics Analysis to Reveal Potential Biomarkers in Patients with Combined Allergic Rhinitis and Asthma Syndrome.

Combined allergic rhinitis and asthma syndrome (CARAS) is a concurrent clinical or subclinical allergic symptom of diseases of the upper and lower respiratory tract. This study is the first to explore the expression profiles of mRNA, lncRNA, and circRNA in CARAS using RNA sequencing, which may provide insight into the mechanisms underlying CARAS. Whole blood samples from nine participants (three CARAS patients, three AR patients, and three normal control participants) were subjected to perform RNA sequencing, followed by identification of differentially expressed lncRNAs (DElncRNAs), circRNAs (DEcircRNAs) and mRNAs (DEmRNAs). Then, lncRNA/circRNA-mRNA regulatory pairs were constructed, followed by functional analysis, immune infiltration analysis, drug prediction, and expression validation with RT-qPCR and ELISA. The results showed that 61 DEmRNAs, 23 DElncRNAs and 3 DEcircRNAs may be related to the occurrence and development of CARAS. KRT8 may be implicated in the development of AR into CARAS. Three immunity-related mRNAs (IDO1, CYSLTR2, and TEC) and two hypoxia-related mRNAs (TKTL1 and VLDLR) were associated with the occurrence and development of CARAS. TEC may be considered a drug target for Dasatinib in treating CARAS. Several lncRNA/circRNA-mRNA regulatory pairs were identified in CARAS, including LINC00452/MIR4280HG/hsa_circ_0007272/hsa_circ_0070934-CLC, HEATR6-DT/LINC00639/LINC01783/hsa_circ_0008903-TEC, RP11-71L14.3-IDO1/SMPD3, RP11-178F10.2-IDO1/HRH4, and hsa_circ_0008903-CYSLTR2, which may indicate potential regulatory effects of lncRNAs/circRNAs in CARAS. Dysregulated levels of immune cell infiltration may be closely related to CARAS. The regulating effect of lncRNA/circRNA-immunity/hypoxia-related mRNA regulatory pairs may be involved in the occurrence and development of CARAS.

Circulating Oncometabolite 2-hydroxyglutarate as a Potential Biomarker for Isocitrate Dehydrogenase (IDH1/2) Mutant Cholangiocarcinoma.

Isocitrate dehydrogenase (IDH) enzymes catalyze the decarboxylation of isocitrate to alpha-ketoglutarate (αKG). IDH1/2 mutations preferentially convert αKG to R-2-hydroxyglutarate (R2HG), resulting in R2HG accumulation in tumor tissues. We investigated circulating 2-hydroxyglutate (2HG) as potential biomarkers for patients with IDH-mutant (IDHmt) cholangiocarcinoma (CCA). R2HG and S-2-hydroxyglutarate (S2HG) levels in blood and tumor tissues were analyzed in a discovery cohort of patients with IDHmt glioma and CCA. Results were validated in cohorts of patients with CCA and clear-cell renal cell carcinoma. The R2HG/S2HG ratio (rRS) was significantly elevated in tumor tissues, but not in blood for patients with IDHmt glioma, while circulating rRS was elevated in patients with IDHmt CCA. There were overlap distributions of circulating R2HG and total 2HG in patients with both IDHmt and wild-type (IDHwt) CCA, while there was minimal overlap in rRS values between patients with IDHmt and IDHwt CCA. Using the rRS cut-off value of 1.5, the sensitivity of rRS was 90% and specificity was 96.8%. Circulating rRS is significantly increased in patients with IDHmt CCA compare with patients with IDHwt CCA. Circulating rRS is a sensitive and specific surrogate biomarker for IDH1/2 mutations in CCA. It can potentially be used as a tool for monitoring IDH-targeted therapy.

Baseline Values of Circulating IL-6 and TGF-β Might Identify Patients with HNSCC Who Do Not Benefit from Nivolumab Treatment.

The immunotherapy of head and neck cancer induces a limited rate of long-term survivors at the cost of treating many patients exposed to toxicity without benefit, regardless of PD-L1 expression. The identification of better biomarkers is warranted. We analyzed a panel of cytokines, chemokines and growth factors, hereinafter all referred to as 'cytokines', as potential biomarkers in patients with head and neck cancer treated with nivolumab. A total of 18 circulating cytokines were analyzed. Samples were gathered at baseline (T0) and after 3 courses of nivolumab (T1) in patients with relapsed/metastatic disease. The data extracted at T0 were linked to survival; the comparison of T0-T1 explored the effect of immunotherapy. A total of 22 patients were accrued: 64% current heavy smokers, 36% female and 14% had PS = 2. At T0, ROC analysis showed that IL-6, IL-8, IL-10 and TGF-β were higher in patients with poor survival. Cox analysis demonstrated that only patients with the IL-6 and TGF-β discriminate had good or poor survival, respectively. Longitudinal increments of CCL-4, IL-15, IL-2 and CXCL-10 were observed in all patients during nivolumab treatment. In this small population with poor clinical characteristics, this study highlights the prognostic role of IL-6 and TGF-β. Nivolumab treatment is associated with a positive modulation of some Th1 cytokines, but it does not correlate with the outcome.

Next-generation sequencing identifies CDKN2A alterations as prognostic biomarkers in recurrent or metastatic head and neck squamous cell carcinoma predominantly receiving immune checkpoint inhibitors.

This study aimed to identify potential biomarkers in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) and further probe the prognostic implications of CDKN2A mutations, particularly within a subset receiving immunotherapy. In this retrospective single-center study, we evaluated the next-generation sequencing (NGS) data from Foundation Medicine (FM) for patients with recurrent or metastatic HNSCC between January 1, 2019, and December 31, 2021. Patients were stratified based on CDKN2A loss-of-function (LOF) versus wild-type (WT) categorizations, with a focused subgroup analysis on those administered immunotherapy. The study encompassed 77 patients, of which 62 had undergone immunotherapy. The median duration of follow-up was 22.6 months. For the CDKN2A LOF group, the median overall survival (OS) was 16.5 months, contrasted with 30.0 months in the CDKN2A WT group (P=0.014). Notably, female gender (hazard ratio [HR]=4.526, 95% confidence interval [CI]: 1.934-10.180, P=0.0003) and CDKN2A LOF (HR=2.311, 95% CI: 1.156-4.748, P=0.019) emerged as independent risk factors for mortality in patients with recurrent or metastatic HNSCC. Within the immunotherapy subset, the median OS was 11.7 months for the CDKN2A LOF group, and 22.5 months for the CDKN2A WT group (P=0.017). Further, the female gender (HR=4.022, 95% CI: 1.417-10.710, P=0.006), CDKN2A LOF (HR=4.389, 95% CI: 1.782-11.460, P=0.002), and a combined positive score below 1 (HR=17.20, 95% CI: 4.134-79.550, P<0.0001) were identified as significant predictors of mortality among patients with recurrent or metastatic HNSCC receiving immunotherapy. Alterations manifesting as LOF in the CDKN2A gene stand as robust indicators of unfavorable survival outcomes in HNSCC patients, including the subset that underwent immunotherapy.

Lack of Association of Plasma Levels of Soluble Programmed Cell Death Protein 1, Programmed Death-Ligand 1, and CTLA-4 With Survival for Stage II to IIIA NSCLC After Complete Resection and Adjuvant Chemotherapy

IntroductionPerioperative treatment in NSCLC has gained marked attention with the introduction of immune checkpoint inhibitors. Such a paradigm shift has given us additional opportunities to evaluate potential biomarkers in patients with these curable disease stages. MethodsThis study (WJOG12319LTR) was designed as a biomarker study to evaluate whether soluble immune markers were prognostic or predictive on relapse-free survival in patients with stage II to IIIA NSCLC who underwent complete resection and adjuvant chemotherapy with cisplatin plus S-1, which is an oral fluoropyrimidine formulation that consists of tegafur, gimeracil, and oteracil, or S-1 alone in the previous WJOG4107 study. Archived plasma samples were assayed for soluble (s) forms of programmed cell death protein 1 (sPD-1), programmed death-ligand 1(sPD-L1), and CTLA-4 (sCTLA-4) with the highly sensitive HISCL system. Using time-dependent receiver operating characteristic curve analysis, the area under the curves were derived and optimal cutoff values were determined. Using the cutoff values, whether the marker was prognostic or predictive was assessed by survival analysis. ResultsA total of 150 patients were included in the study. The time-dependent receiver operating characteristics analysis revealed that the area under the curves for sPD-1, sPD-L1, and sCTLA-4 were 0.54, 0.51, and 0.58, respectively. The survival analysis did not reject that hazard ratios were 1 in terms of the soluble immune marker and the treatment-marker interaction for all three markers. ConclusionsThere was no proof that circulating concentrations of sPD-1, sPD-L1, and sCTLA-4 were prognostic or predictive factors of the outcome for adjuvant chemotherapy after complete resection in patients with NSCLC.

Characteristics of the pulmonary microbiota in patients with mild and severe pulmonary infection.

Lung infection is a global health problem associated with high morbidity and mortality and increasing rates of hospitalization. The correlation between pulmonary microecology and infection severity remains unclear. Therefore, the purpose of this study was to investigate the differences in lung microecology and potential biomarkers in patients with mild and severe pulmonary infection. Patients with pulmonary infection or suspected infection were divided into the mild group (140 cases) and the severe group (80 cases) according to pneomonia severity index (PSI) scores. Here, we used metagenomic next-generation sequencing (mNGS) to detect DNA mainly from bronchoalveolar lavage fluid (BALF) collected from patients to analyze changes in the lung microbiome of patients with different disease severity. We used the mNGS to analyze the pulmonary microecological composition in patients with pulmonary infection. The results of alpha diversity and beta diversity analysis showed that the microbial composition between mild and severe groups was similar on the whole. The dominant bacteria were Acinetobacter, Bacillus, Mycobacterium, Staphylococcus, and Prevotella, among others. Linear discriminant analysis effect size (LEfSe) results showed that there were significant differences in virus composition between the mild and severe patients, especially Simplexvirus and Cytomegalovirus, which were prominent in the severe group. The random forest model screened 14 kinds of pulmonary infection-related pathogens including Corynebacterium, Mycobacterium, Streptococcus, Klebsiella, and Acinetobacter. In addition, it was found that Rothia was negatively correlated with Acinetobacter, Mycobacterium, Bacillus, Enterococcus, and Klebsiella in the mild group through co-occurrence network, while no significant correlation was found in the severe group. Here, we describe the composition and diversity of the pulmonary microbiome in patients with pulmonary infection. A significant increase in viral replication was found in the severe group, as well as a significant difference in microbial interactions between patients with mild and severe lung infections, particularly the association between the common pathogenic bacteria and Rothia. This suggests that both pathogen co-viral infection and microbial interactions may influence the course of disease. Of course, more research is needed to further explore the specific mechanisms by which microbial interactions influence disease severity.

Clinical significance of MMP-2 and MMP-9 levels as potential biomarkers in patients with breast cancer in Maiduguri – Nigeria

Breast cancer (BC) is a significant public health challenge globally, affecting women of all races and ages. In Nigeria and Sub-Saharan Africa, BC is the most common cancer among women, with high mortality rates. In BC, a number of MMPs are overexpressed thereby causing tissue disruption and making tumour cell’s capable of invasion and metastasis. IDCA, ILCA and MCA are histological types of BCs that were seen in this study, they are classified into grade 1, 2 and 3 tumours. This present study investigated the expression of Matrix Metalloproteinases -2 and -9 in formalin fixed tissues from BC patients and correlated with some clinico-pathological parameters. Thirty-four (34) BC samples were analysed for the expression of the MMP-2 and -9 genes using real-time qPCR. The data analyses were performed using SPSS. The real-time qPCR results indicated that there was downregulation of MMP-2 in grade -2 cancer samples and upregulation of MMP-9 in both grade-2 and -3 samples when compared to normal breast tissues. MMP-2 and -9 were expressed in all the histological types we found during this study (IDCA – 78.1%, ILCA – 12.5% and MCA – 9.4%). Therefore, this differential regulation of MMP – 2 found during our studies on BC tissues can be an indication of their roles in tumour invasion, also the overexpression of MMP-9 in higher grades might be an indicator in tumour invasion and metastasis. Thus, MMP-2 and -9 are of immense significance to be considered and used as drug targets and diagnostic markers.

Plasma proteoglycan 4: a novel biomarker for acute lung injury after pediatric cardiac surgery.

Identification of biological molecules related to post cardiopulmonary bypass (CPB) lung injury could help diagnose, predict and potentially impact patient's clinical course after cardiac surgery. Proteoglycan 4 (PRG4) initially identified as potential biomarker for patients with prolonged mechanical ventilation following CPB in a prior study. To further validate these findings, we sought to understand the association of lower plasma PRG4 with prolonged mechanical ventilation and worse lung compliance in a larger cohort of pediatric patients post CPB. Retrospective chart review study. Pediatric Cardiac Intensive Care Unit, Tertiary Hospital. Infants <1 year old with tetralogy of Fallot, ventricular septal defect, or atrioventricular septal defect who underwent surgical repair 2012-2020 and had stored plasma samples in our biorepository were screened for inclusion. Patients with mechanical ventilation before surgery were excluded. Patients were divided into quartiles based on postoperative duration of mechanical ventilation (control <25th percentile, study >75th percentile). Preoperative and 48-hour postoperative samples for each cohort (20 patients each) were tested for PRG4 level using enzyme-linked immunosorbent assay (ELISA) technique. Study group had lower lung compliance, higher mean airway pressure and higher oxygen need postoperative when compared to control group. Plasma PRG4 levels before surgery and 48 hours postoperative were lower in study group compared to control group (P=0.0232 preoperative; P=0.0016 postoperative). Plasma PRG4 levels were compared preoperative to PRG4 levels postoperative in both group, there was no statistically significant difference (study group: P=0.0869; control group: P=0.6500). Lower levels of plasma PRG4 is associated with longer duration of mechanical ventilation, worse ventilator compliance and higher oxygen requirement after cardiac surgery in our patient population. Further validation of this finding in a larger and more diverse patient population is necessary prior to its application at the bedside.

Feasibility of using volatile urine fingerprints for the differentiation of sexually transmitted infections

Sexually transmitted infections (STIs) are a public health problem worldwide, and current diagnostic methods have certain limitations. In recent years, volatile organic compounds (VOCs) have been studied as an alternative diagnostic method. Due to this, this study aimed to detect, in vaginal swabs and urine samples, VOCs emitted by highly prevalent STIs-causing bacteria (Chlamydia trachomatis, Mycoplasma genitalium, and Neisseria gonorrhoeae) to identify potential biomarkers that allow the detection of these STIs. VOCs detected in urine samples showed a better differentiation of patients with STIs due to C. trachomatis from those not infected, with 2,6-dimethyl-4-heptanone as the volatile compound most related to the presence of this bacterium. Among the VOCs most related to M. genitalium in urine, 4-methyltetradecane and 2-methylpentadecane stood out, while 3,4,4-trimethyl-2-cyclohexen-1-one was the VOC most closely related to N. gonorrhoeae infection. Moreover, C12 alcohols were the main VOC family associated with positive samples in all three bacteria, which could indicate the presence of aldehyde reductases in their metabolism. In contrast, alcohols such as 3-methyl-1-heptanol and 1-octanol, as well as dimethyl esters, were more associated with negative samples and may be useful in ruling out an STI caused by one of these three bacteria. In short, the VOCs identified as potential biomarkers in patients with infection by C. trachomatis, M. genitalium, or N. gonorrhoeae could be used in the early diagnosis of these STIs, quickly interrupting the chain of transmission, especially interesting in asymptomatic patients.Key points• Sexually transmitted infections are a serious public health problem worldwide.• The study of VOCs in multiple infections is increasing in recent years.• The identification of volatile biomarkers could allow new diagnostic methods.Graphical abstract

Serum versican as a potential biomarker in patients with uterine fibroids: A study from Eastern India.

Versican is a chondroitin sulphate proteoglycan with raised expression at site of inflammation, and uterine fibroids are associated with local inflammation. Hence, this study aimed to estimate serum Versican levels in pre-menopausal women with uterine fibroids to evaluate its diagnostic efficiency. This case-control study included forty uterine fibroid cases and 40 healthy controls. Cases clinically evaluated with USG findings, that is number, location of fibroid and volume calculated by prolate ellipse formula a × b × c × 0.523 (a - height, b - width, c - depth). Biochemical investigations, that is serum Versican levels, were estimated by ELISA with total cholesterol, HDLc and LDLc. Triglycerides by fully automated chemistry analysers. Serum biochemical parameters were compared and correlated with volume of fibroid. Area under receiver operating characteristic curve was calculated along with cut-off value to determine diagnostic potential of Versican, differentiating women with fibroids. In the present study, patients with fibroids had decreased levels of serum Versican (79.43 ± 18.60) as compared to healthy controls (101.81 ± 28.24, P < 0.001). There was a statistically significant negative correlation (r = - 0. 307, P = 0.04) between serum Versican level and volume of fibroid. Area under ROC was 0.726 (95% CI: 0.616-0.836; P = 0.001). The best cut-off value for serum Versican level was 96.90 ng/ml with 90% sensitivity and 48% specificity. Serum Versican levels were found significantly lower in women with fibroid with a negative correlation with volume of fibroid uterus. Furthermore, extensive study would help in substantiating diagnostic potential of serum Versican in fibroid uterus patients.

Oral Spirochete Treponema denticola Intraoral Infection Reveals Unique miR-133a, miR-486, miR-126-3p, miR-126-5p miRNA Expression Kinetics during Periodontitis.

miRNAs are major regulators of eukaryotic gene expression and host immunity, and play an important role in the inflammation-mediated pathways in periodontal disease (PD) pathogenesis. Expanding our previous observation with the global miRNA profiling using partial human mouth microbes, and lack of in vivo studies involving oral spirochete Treponema denticola-induced miRNAs, this study was designed to delineate the global miRNA expression kinetics during progression of periodontitis in mice infected with T. denticola by using NanoString nCounter® miRNA panels. All of the T. denticola-infected male and female mice at 8 and 16 weeks demonstrated bacterial colonization (100%) on the gingival surface, and an increase in alveolar bone resorption (p < 0.0001). A total of 70 miRNAs with at least 1.0-fold differential expression/regulation (DE) (26 upregulated and 44 downregulated) were identified. nCounter miRNA expression profiling identified 13 upregulated miRNAs (e.g., miR-133a, miR-378) and 25 downregulated miRNAs (e.g., miR-375, miR-34b-5p) in T. denticola-infected mouse mandibles during 8 weeks of infection, whereas 13 upregulated miRNAs (e.g., miR-486, miR-126-5p) and 19 downregulated miRNAs (miR-2135, miR-142-3p) were observed during 16 weeks of infection. One miRNA (miR-126-5p) showed significant difference between 8 and 16 weeks of infection. Interestingly, miR-126-5p has been presented as a potential biomarker in patients with periodontitis and coronary artery disease. Among the upregulated miRNAs, miR-486, miR-126-3p, miR-126-5p, miR-378a-3p, miR-22-3p, miR-151a-3p, miR-423-5p, and miR-221 were reported in human gingival plaques and saliva samples from periodontitis and with diabetes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed various functional pathways of DE miRNAs, such as bacterial invasion of epithelial cells, Ras signaling, Fc gamma R-mediated phagocytosis, osteoclast differentiation, adherens signaling, and ubiquitin mediated proteolysis. This is the first study of DE miRNAs in mouse mandibles at different time-points of T. denticola infection; the combination of three specific miRNAs, miR-486, miR-126-3p, and miR-126-5p, may serve as an invasive biomarker of T. denticola in PD. These miRNAs may have a significant role in PD pathogenesis, and this research establishes a link between miRNA, periodontitis, and systemic diseases.

Serum matrix metalloproteinase-7: a potential biomarker in patients with Lynch Syndrome.

The expression of tissue and serum matrix metalloproteinase-7 (MMP-7) was shown to be elevated both in colon cancer and dysplastic lesions. We aimed to evaluate, for the first time, its role as a diagnostic marker in Lynch syndrome (LS) carriers, a hereditary syndrome with predisposition to colon cancer. This was a case control study. Baseline serum MMP-7 levels were determined by ELISA in 40 colon cancer patients, 62 LS-carriers and 60 healthy controls. Retrieved data from medical files included demographics, background diseases, clinical data regarding tumor characteristics and genetic data. We assessed the association of serum MMP-7 levels with different variables in the study cohort using linear regression model adjusted for potential confounders. In crude analysis, serum MMP-7 levels were significantly higher in colon cancer group compared to LS-carriers and controls [median (IQR) 4.1 ng/ml (2.7-6.0), 2.3 ng/ml (1.7-3.1), 2.5 ng/ml (1.5-3.7), respectively; p value - p < 0.001) while there was no difference between the two last groups (p value = 0.583). However, after adjusting for age and gender, LS-carriers' patients had 18% higher concentrations of serum MMP-7 compared to healthy controls (p value = 0.037), while colon cancer patients had 50% higher serum MMP-7 level in comparison to healthy controls (p value < 0.001). Additionally, age was positively associated with higher serum MMP-7 levels across all study groups (r = 0.67, p value < 0.001). In contrast, no correlation was observed between serum MMP-7 and either tumor staging and gene mutation. Age-adjusted serum MMP-7 levels in asymptomatic LS carriers are higher than its levels in healthy population. While in colon cancer, MMP-7 higher level probably reflects the tumor burden and may have a prognostic effect, its significance and clinical applicability as a biomarker for tumorigenesis in LS is less clear and should be elucidated.

Interleukin 5 Receptor Subunit Alpha Expression as a Potential Biomarker in Patients with Nasal Polyposis.

Chronic Rhinosinusitis with Nasal Polyposis (CRSwNP) affects the quality of life of patients suffering from it. The search for a suitable biomarker has been conducted over the last decades. Interleukin 5 receptor subunit alpha (IL-5Rα) involves the activation, maintenance, and survival of eosinophils, which are highly tied to chronic inflammatory processes of the airways, like asthma or CRSwNP. In this study, we evaluate the utility of IL5RA as a genetic biomarker in CRSwNP. IL5RA mRNA expression level was analyzed in different groups of patients by performing qPCR assays. A significant increase in IL5RA expression was observed in CRSwNP patients, especially those with asthma and atopy. We found differences in expression levels when comparing groups with or without polyposis or asthma, as well as some atypical cases related to eosinophil levels. That opens a path to future studies to further characterize groups of patients with common features in the context of pharmacogenetics and in an era towards developing a more precise personalized treatment with IL-5Rα as a therapeutic target for CRSwNP.

Identification of sterile a-motif domain-containing 9-like as a potential biomarker in patients with cutaneous melanoma.

Skin cutaneous melanoma (SKCM) is one of the most aggressive malignancies, accounting for approximately 75% of skin cancer-related fatalities annually. Sterile a-motif domain-containing 9-like (SAMD9L) has been found to regulate cell proliferation and suppress the neoplastic phenotype, but its specific role in SKCM remains unknown. To investigate the cancer-associated immunology of SKCM and the role of SAMD9L in tumor progression, we conducted an integrative bioinformatics analysis that revealed elevated expression levels of SAMD9L in SKCM. ROC curves and survival analyses confirmed the considerable diagnostic and prognostic abilities of SAMD9L. Moreover, a real-world cohort of 35 SKCM patients from the First Affiliated Hospital of Soochow University showed that higher expression levels of SAMD9L were associated with better prognosis. We performed validation experiments, including cell culture, generation of lentiviral-transfected SKCM cell lines, cell proliferation assay, and transwell assay, which demonstrated that down-regulation of SAMD9L significantly promoted proliferation and migration capacities of SKCM cells. Additionally, SAMD9L expression was found to be strongly linked to immune infiltration. Our results revealed a positive correlation between SAMD9L and XAF1 expression, suggesting that SAMD9L may serve as a prospective prognostic indicator of SKCM with co-expressed XAF1 gene. In summary, our findings indicate that SAMD9L may serve as a promising prognostic and therapeutic biomarker and play a critical role in tumor-immune interactions in SKCM.