scholarly journals Discovery of N-glycan Biomarkers for the Canine Osteoarthritis

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 199
Author(s):  
Hyunjun Lee ◽  
Ahyun Lee ◽  
Nari Seo ◽  
Jiwon Oh ◽  
Oh-Kyeong Kweon ◽  
...  

Protein glycosylation is a post-translational modification that impacts on protein activity, stability, and interactions. It was sensitively altered by the cellular state and, therefore, is now used for a diagnostic or prognostic indicator of various human diseases such as cancer. To evaluate the clinical feasibility in the veterinary area, the N-glycan biomarkers were discovered from canine serum for the diagnosis of osteoarthritis (OA), which is one of the most common diseases of dogs. N-glycome was obtained from 20 μL of canine serum by the enzymatic cleavage followed by the purification and enrichment using solid-phase extraction. Independent compositions of 163 and 463 N-glycans were found from healthy control (n = 41) and osteoarthritis patients (n = 92), respectively. Initially, 31 of the potential biomarkers were screened by the p-values below 1.0 × 10−10 from ANOVA. Then, the area under the curve (AUC) and the intensity ratio between OA patient and healthy control (P/C ratio) were calculated. Considering the diagnostic efficacy, the AUC bigger than 0.9 and the P/C ratio larger than 3.0 were used to discover 16 N-glycans as diagnostic biomarkers. Particularly, five of the diagnostic biomarkers were AUC above 0.99 and three of N-glycans had AUC 1.0. The results suggest a clear possibility for N-glycan biomarkers to be used as a clinical tool in the veterinary medical area enabling to provide objective and non-invasive diagnostic information.

Author(s):  
Jian Zheng ◽  
Xiong Ye ◽  
Yuxia Zhao ◽  
Mudan He ◽  
Hui Xiao

Abstract Objective: Solitary pulmonary nodules (SPNs) is a common radiographic finding and require further evaluation because of the possibility of lung cancer. This study aimed to determine the sensitivity and specificity of circulating tumour cells (CTCs) as a marker for the diagnosis of SPNs and the integration of CTCs, carcinoembryonic antigen (CEA) and imaging findings to improve the sensitivity and specificity of diagnosis in patients with SPNs suspected of being lung cancer.Method: For the serum biomarker assay, the concentration of CEA was measured by an automated electrochemiluminescence analyzer. CTCs were collected from 6 ml of blood by i-FISH method, which detects the gene copy number in eight chromosomes and the tumour-associated antigen CK18.Results: With a threshold of 6 CTC units, the method showed a sensitivity of 67.1% and a specificity of 56.5% in the diagnosis of NSCLC, especially in the upper lobe, in which the diagnostic strength was the highest (P < 0.01). CTCs, CEA and nodule type had the highest diagnostic efficacy (area under the curve, 0.827; 95% confidence interval, 0.752-0.901) in patients with SPNs being suspected lung cancer. Combining CTCs (cut-off value 12 units) with CEA (1.78 ng/ml), the method showed a sensitivity of 77.8% and a specificity of 90% in the diagnosis of NSCLC, especially in the upper lobe, sub solid nodules and nodules ≥8 mm.Conclusion: Our results demonstrated that CTCs are feasible diagnostic biomarkers in patients with SPNs, especially in the upper lobe. Furthermore, CTCs combined with CEA showed higher diagnostic efficacy in the upper lobe, sub solid nodules and nodules ≥8 mm.


2021 ◽  
Author(s):  
Li Huang ◽  
Zuojian Hu ◽  
Ruixian Luo ◽  
Hailan Li ◽  
Ziji Yang ◽  
...  

Abstract Background: Ample evidence has revealed that the lymphocyte-to-monocyte ratio (LMR), albumin-to-globulin ratio (AGR) and mean platelet volume (MPV) are cancer-related inflammatory markers. The present study aimed to assess a better diagnostic marker for the progression of colon cancer. Methods: This retrospective study enrolled 251 patients with colon cancer, 171 patients with benign colon diseases, and 187 healthy control subjects from January 2012 to September 2020. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to determine the diagnostic values of the selected inflammatory index.Results: The levels of LMR, AGR and MPV were decreased in the colon cancer group compared with the healthy control and benign colon disease groups. The LMR, AGR and MPV were all correlated with tumor size. Moreover, LMR and AGR was associated with lymph node metastasis and clinical stage, AGR was related to distant metastasis. Both the LMR (p = 0.030) and AGR (p = 0.005) were negatively correlated with the concentration of carcinoembryonic antigen (CEA). The AUC value of MPV combined with CEA had a good diagnostic ability for distinguishing controls from colon cancer cases (AUC = 0.950) and patients with benign colon diseases (AUC = 0.886). Meanwhile, the combination of LMR or AGR with CEA could enhance the diagnostic efficacy (AUC; 0.746 for LMR + CEA, 0.737 for AGR + CEA) of detecting colon cancer from benign colon diseases. Conclusions: CEA combined with the selected inflammatory index may be used as better blood-based biomarkers in the progression of colon cancer patients.


Author(s):  
Gregory Fedorchak ◽  
Aakanksha Rangnekar ◽  
Cayce Onks ◽  
Andrea C. Loeffert ◽  
Jayson Loeffert ◽  
...  

Abstract Objective The goals of this study were to assess the ability of salivary non-coding RNA (ncRNA) levels to predict post-concussion symptoms lasting ≥ 21 days, and to examine the ability of ncRNAs to identify recovery compared to cognition and balance. Methods RNA sequencing was performed on 505 saliva samples obtained longitudinally from 112 individuals (8–24-years-old) with mild traumatic brain injury (mTBI). Initial samples were obtained ≤ 14 days post-injury, and follow-up samples were obtained ≥ 21 days post-injury. Computerized balance and cognitive test performance were assessed at initial and follow-up time-points. Machine learning was used to define: (1) a model employing initial ncRNA levels to predict persistent post-concussion symptoms (PPCS) ≥ 21 days post-injury; and (2) a model employing follow-up ncRNA levels to identify symptom recovery. Performance of the models was compared against a validated clinical prediction rule, and balance/cognitive test performance, respectively. Results An algorithm using age and 16 ncRNAs predicted PPCS with greater accuracy than the validated clinical tool and demonstrated additive combined utility (area under the curve (AUC) 0.86; 95% CI 0.84–0.88). Initial balance and cognitive test performance did not differ between PPCS and non-PPCS groups (p > 0.05). Follow-up balance and cognitive test performance identified symptom recovery with similar accuracy to a model using 11 ncRNAs and age. A combined model (ncRNAs, balance, cognition) most accurately identified recovery (AUC 0.86; 95% CI 0.83–0.89). Conclusions ncRNA biomarkers show promise for tracking recovery from mTBI, and for predicting who will have prolonged symptoms. They could provide accurate expectations for recovery, stratify need for intervention, and guide safe return-to-activities.


2021 ◽  
Vol 14 (7) ◽  
pp. 618
Author(s):  
Michele Stella ◽  
Luca Falzone ◽  
Angela Caponnetto ◽  
Giuseppe Gattuso ◽  
Cristina Barbagallo ◽  
...  

Glioblastoma multiforme (GBM) is the most frequent and deadly human brain cancer. Early diagnosis through non-invasive biomarkers may render GBM more easily treatable, improving the prognosis of this currently incurable disease. We suggest the use of serum extracellular vesicle (sEV)-derived circular RNAs (circRNAs) as highly stable minimally invasive diagnostic biomarkers for GBM diagnosis. EVs were isolated by size exclusion chromatography from sera of 23 GBM and 5 grade 3 glioma (GIII) patients, and 10 unaffected controls (UC). The expression of two candidate circRNAs (circSMARCA5 and circHIPK3) was assayed by droplet digital PCR. CircSMARCA5 and circHIPK3 were significantly less abundant in sEVs from GBM patients with respect to UC (fold-change (FC) of −2.15 and −1.92, respectively) and GIII (FC of −1.75 and −1.4, respectively). Receiver operating characteristic curve (ROC) analysis, based on the expression of sEV-derived circSMARCA5 and circHIPK3, allowed us to distinguish GBM from UC (area under the curve (AUC) 0.823 (0.667–0.979) and 0.855 (0.704 to 1.000), with a 95% confidence interval (CI), respectively). Multivariable ROC analysis, performed by combining the expression of sEV-derived circSMARCA5 and circHIPK3 with preoperative neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR) and lymphocyte to monocyte (LMR) ratios, three known diagnostic and prognostic GBM markers, allowed an improvement in the GBM diagnostic accuracy (AUC 0.901 (0.7912 to 1.000), 95% CI). Our data suggest sEV-derived circSMARCA5 and circHIPK3 as good diagnostic biomarkers for GBM, especially when associated with preoperative NLR, PLR and LMR.


Diagnostics ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 643
Author(s):  
Francis Mugeni Wanyama ◽  
Véronique Blanchard

Ovarian cancer remains one of the most common causes of death among gynecological malignancies afflicting women worldwide. Among the gynecological cancers, cervical and endometrial cancers confer the greatest burden to the developing and the developed world, respectively; however, the overall survival rates for patients with ovarian cancer are worse than the two aforementioned. The majority of patients with ovarian cancer are diagnosed at an advanced stage when cancer has metastasized to different body sites and the cure rates, including the five-year survival, are significantly diminished. The delay in diagnosis is due to the absence of or unspecific symptoms at the initial stages of cancer as well as a lack of effective screening and diagnostic biomarkers that can detect cancer at the early stages. This, therefore, provides an imperative to prospect for new biomarkers that will provide early diagnostic strategies allowing timely mitigative interventions. Glycosylation is a protein post-translational modification that is modified in cancer patients. In the current review, we document the state-of-the-art of blood-based glycomic biomarkers for early diagnosis of ovarian cancer and the technologies currently used in this endeavor.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Bo Yao ◽  
Wen-juan Liu ◽  
Di Liu ◽  
Jin-yan Xing ◽  
Li-juan Zhang

Abstract Background Early diagnosis of sepsis is very important. It is necessary to find effective and adequate biomarkers in order to diagnose sepsis. In this study, we compared the value of sialic acid and procalcitonin for diagnosing sepsis. Methods Newly admitted intensive care unit patients were enrolled from January 2019 to June 2019. We retrospectively collected patient data, including presence of sepsis or not, procalcitonin level and sialic acid level. Receiver operating characteristic curves for the ability of sialic acid, procalcitonin and combination of sialic acid and procalcitonin to diagnose sepsis were carried out. Results A total of 644 patients were admitted to our department from January 2019 to June 2019. The incomplete data were found in 147 patients. Finally, 497 patients data were analyzed. The sensitivity, specificity and area under the curve for the diagnosis of sepsis with sialic acid, procalcitonin and combination of sialic acid and procalcitonin were 64.2, 78.3%, 0.763; 67.9, 84.0%, 0.816 and 75.2, 84.6%, 0.854. Moreover, sialic acid had good values for diagnosing septic patients with viral infection, with 87.5% sensitivity, 82.2% specificity, and 0.882 the area under the curve. Conclusions Compared to procalcitonin, sialic acid had a lower diagnostic efficacy for diagnosing sepsis in critically ill patients. However, the combination of sialic acid and procalcitonin had a higher diagnostic efficacy for sepsis. Moreover, sialic acid had good value for diagnosing virus-induced sepsis.


Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 829
Author(s):  
Yana Kogan ◽  
Edmond Sabo ◽  
Majed Odeh

Objectives: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort. Methods: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. Results: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group (p < 0.0001). No significant difference was found between the two groups for levels of CRPr (p = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and p < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and p < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and p < 0.0001. Conclusions: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.


2017 ◽  
Vol 104 (1) ◽  
pp. 35-41 ◽  
Author(s):  
A Kern ◽  
E Barabás ◽  
A Balog ◽  
Sz Burcsár ◽  
M Kiszelák ◽  
...  

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disorder. Thrombotic events occur at a higher incidence among SLE patients. The investigation of thrombin generation (TG) with calibrated automated thrombogram (CAT) test as a global hemostasis assay is applicable for the overall functional assessment of the hemostasis. The aim of this study was to characterize the hemostatic alterations observed in SLE by CAT assay. In this study, CAT parameters and basic coagulation parameters of SLE patients (n = 22) and healthy control subjects (n = 34) were compared. CAT area under the curve (i.e., endogenous thrombin potential) was lower than normal in SLE (807 vs. 1,159 nM*min, respectively), whereas other CAT parameters (peak, lag time, time to peak, and velocity index) and the basic coagulation tests were within the normal range. The presence of anti-phospholipid antibodies and the applied therapy was not associated with hemostasis parameters in SLE. We concluded that the reported high risk of thrombosis is not related to TG potential.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiang Chen ◽  
Hongyu Li ◽  
Wenda Xu ◽  
Xiaozhong Guo

Abstract Background Pancreatic cancer (PC) is a devastating disease that has a poor prognosis and a total 5-year survival rate of around 5%. The poor prognosis of PC is due in part to a lack of suitable biomarkers that can allow early diagnosis. The lysophospholipase autotaxin (ATX) and its product lysophosphatidic acid (LPA) play an essential role in disease progression in PC patients and are associated with increased morbidity in several types of cancer. In this study, we evaluated both the potential role of serum LPA and ATX as diagnostic markers in PC and their prognostic value for PC either alone or in combination with CA19-9. Methods ATX, LPA and CA19-9 levels were evaluated using ELISA of serum obtained from PC patients (n = 114) healthy volunteers (HVs: n = 120) and patients with benign pancreatic diseases (BPDs: n = 94). Results Serum levels of ATX, LPA and CA19-9 in PC patients were substantially higher than that for BPD patients or HVs (p < 0.001). The sensitivity of LPA in early phase PC was 91.74% and the specificity of ATX was 80%. The levels of ATX, LPA and CA19-9 were all substantially higher for early stage PC patients compared to levels in serum from BPD patients and HVs. The diagnostic efficacy of CA19-9 for PC was significantly enhanced by the addition of ATX and LPA (p = 0.0012). Conclusion Measurement of LPA and ATX levels together with CA19-9 levels can be used for early detection of PC and diagnosis of PC in general.


Diagnostics ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 109 ◽  
Author(s):  
Ukweh ◽  
Ugbem ◽  
Okeke ◽  
Ekpo

Background: Ultrasound is operator-dependent, and its value and efficacy in fetal morphology assessment in a low-resource setting is poorly understood. We assessed the value and efficacy of fetal morphology ultrasound assessment in a Nigerian setting. Materials and Methods: We surveyed fetal morphology ultrasound performed across five facilities and followed-up each fetus to ascertain the outcome. Fetuses were surveyed in the second trimester (18th–22nd weeks) using the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guideline. Clinical and surgical reports were used as references to assess the diagnostic efficacy of ultrasound in livebirths, and autopsy reports to confirm anomalies in terminated pregnancies, spontaneous abortions, intrauterine fetal deaths, and still births. We calculated sensitivity, specificity, positive and negative predictive values, Area under the curve (AUC), Youden index, likelihood ratios, and post-test probabilities. Results: In total, 6520 fetuses of women aged 15–46 years (mean = 31.7 years) were surveyed. The overall sensitivity, specificity, and AUC were 77.1 (95% CI: 68–84.6), 99.5 (95% CI: 99.3–99.7), and 88.3 (95% CI: 83.7–92.2), respectively. Other performance metrics were: positive predictive value, 72.4 (95% CI: 64.7–79.0), negative predictive value, 99.6 (95% CI: 99.5–99.7), and Youden index (77.1%). Abnormality prevalence was 1.67% (95% CI: 1.37–2.01), and the positive and negative likelihood ratios were 254 (95% CI: 107.7–221.4) and 0.23 (95% CI: 0.16–0.33), respectively. The post-test probability for positive test was 72% (95% CI: 65–79). Conclusion: Fetal morphology assessment is valuable in a poor economics setting, however, the variation in the diagnostic efficacy across facilities and the limitations associated with the detection of circulatory system anomalies need to be addressed.


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