Valuable Diagnostic Biomarker Research Articles

The Level of Expression and Diagnostic Value of Biomarkers in Tuberculous Pleurisy

Objective: Observe and analyze the clinical significance of the differences in the expression levels of sCD163, haptoglobin and cytokines. Methods: 120 patients with tuberculous pleural effusion diagnosed in our hospital from January 2019 to December 2021 were randomly selected as the experimental group. On the other hand, 40 patients with non-tuberculous pleural effusion admitted in the same period were selected as the control group. The expression levels of sCD163, haptoglobin and cytokines were observed and analyzed. Results: The expression levels of sCD163 (?g/mL), haptoglobin (g/L), IL-6 (pg/mL) and IL-12 (pg/mL) of the control group were 31.26 ± 14.12, 32.14 ± 18.79, 401.23 ± 24.36 and 1.32 ± 0.14, respectively. As for the experimental group, the expression levels of sCD163 (?g/mL), haptoglobin (g/L), IL-6 (pg/mL) and IL-12 (pg/mL) were 74.12 ± 14.78, 113.25 ± 19.45, 612.12 ± 36.98 and 4.12 ± 0.56 respectively, and p < 0.05 which shows that the data was statistically significant. Conclusion: The level of inflammatory cytokines in the pleural fluid of tuberculous pleural effusion patients are higher, which can be used for the diagnosis of auxiliary tuberculous pleurisy. Tuberculous pleural effusion patients has a significantly increased expression levels of sCD163 and haptoglobin in the pleural fluid. The combination of sCD163 and haptoglobin in the diagnosis of tuberculous pleural effusion has higher clinical diagnostic value, and sCD163 and haptoglobin are not interfered by inflammatory factors in the diagnosis of tuberculous pleural effusion

Research progress regarding long-chain non-coding RNA in lung cancer: a narrative review

Background and ObjectiveLung cancer is the main cause of cancer-related death worldwide, and its incidence rate is high. Traditional methods of lung cancer screening, such as those based on X-ray, low-dose computed tomography (LDCT), positron emission computed tomography (PET/CT), electronic bronchoscopy, and serum tumor markers were not satisfied with the urgent need in improving the patient survival rate. Thus, biomarkers for early diagnosis and prognosis of lung cancer are extremely needed. Studies have identified a variety of long-chain non-coding RNAs (lncRNAs) that are expressed at abnormal levels in patients with lung cancer which was believed as a potential biomarker for the diagnosis and prognostic evaluation of lung cancer. This review aims to discuss the role of lncRNAs in non-small cell lung cancer (NSCLC), so as to provide insights into the prognosis of lung cancer.MethodsWe searched PubMed database of the related scientific researches with outcomes from 09/16/2011 to 05/02/2022 focusing on lncRNA application in lung cancer via searching terms of “lncRNA AND lung cancer”, “lncRNA AND non-small cell lung cancer”, “lncRNA AND drug resistance”, “lncRNA AND radio sensitivity”. Published articles written in English available to readers were considered.Key Content and FindingsWe summarized significantly differentially-expressed lncRNAs in lung cancer tissues compared with healthy individuals and normal tissues which would become potential biomarkers for lung cancer diagnosis and therapeutic target as a non-invasive detection method.ConclusionsLncRNAs might be valuable potential diagnostic biomarkers of lung cancer progression.

Proteomic profiling of plasma exosomes from patients with B-cell acute lymphoblastic leukemia

We aimed to comprehensively investigate the proteomic profile and underlying biological function of exosomal proteins associated with B-cell acute lymphoblastic leukemia. Exosomes were isolated from plasma samples collected from five patients with B-ALL and five healthy individuals, and their protein content was quantitatively analyzed by liquid chromatography with tandem mass spectrometry. A total of 342 differentially expressed proteins were identified in patients with B-ALL. The DEPs were mainly associated with protein metabolic processes and protein activity regulation and were significantly enriched in the Notch and autophagy pathways. Furthermore, we found that ADAM17 and ATG3 were upregulated in patients with B-ALL and enriched in the Notch and autophagy pathways, respectively. Further western blot analysis of exosomes collected from additional 18 patients with B-ALL and 10 healthy controls confirmed that both ADAM17 and ATG3 were overexpressed in exosomes derived from patients with B-ALL (p < 0.001). The areas under the curves of ADAM17 and ATG3 were 0.989 and 0.956, respectively, demonstrating their diagnostic potential. In conclusion, ADAM17 and ATG3 in plasma-derived exosomes may contribute to the progression of B-ALL by regulating the Notch and autophagy pathways. Hence, these proteins may represent valuable diagnostic biomarkers and therapeutic targets for B-ALL.

APRIL and BAFF play a key role in differentiating vitreoretinal lymphoma from uveitis

BackgroundEarly diagnosis of vitreoretinal lymphoma (VRL) is critical for the successful treatment of this rare intraocular malignancy. However, fast and reliable diagnosis of VRL in patients presenting with intermediate or posterior non-infectious uveitis remains a challenge. A proliferation-inducing ligand (APRIL) and B-cell activating factor (BAFF) are vital factors in the pathophysiology, diagnosis, and prognosis of primary central nervous system lymphoma (PCNSL) and systemic autoimmune diseases. However, their utility as biomarkers for the diagnosis of VRL and uveitis remains unclear. MethodsIn this retrospective study, we analyzed APRIL and BAFF levels in the aqueous humor (AH) of 43 eyes of 40 patients, including 23 eyes of 20 patients with VRL, eight eyes of eight patients with uveitis, and 12 eyes of 12 patients with other ocular diseases (OODs). Additionally, we measured their levels after induction of chemotherapy in five eyes of five patients with VRL. ResultsAH levels of APRIL reliably distinguished VRL from uveitis, with a specificity of 78.3% and sensitivity of 75%. BAFF also showed similar potential. Serial AH analysis of patients with VRL during chemotherapy demonstrated a corresponding decline in AH levels of APRIL and BAFF. ConclusionThis study extends the spectrum of valuable diagnostic biomarkers for VRL and uveitis. In patients with uveitis, the assessment of AH APRIL may help accelerate the diagnosis of VRL. Moreover, our results underline the important role of APRIL and BAFF in therapeutic monitoring of VRL.

ESRRG, ATP4A, and ATP4B as Diagnostic Biomarkers for Gastric Cancer: A Bioinformatic Analysis Based on Machine Learning.

Based on multiple bioinformatics methods and machine learning techniques, this study was designed to explore potential hub genes of gastric cancer with a diagnostic value. The novel biomarkers were detected through multiple databases of gastric cancer–related genes. The NCBI Gene Expression Omnibus (GEO) database was used to obtain gene expression files. Three hub genes (ESRRG, ATP4A, and ATP4B) were detected through a combination of weighted gene co-expression network analysis (WGCNA), gene–gene interaction network analysis, and supervised feature selection method. GEPIA2 was used to verify the differences in the expression levels of the hub genes in normal and cancer tissues in the RNA-seq levels of Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. The objectivity of potential hub genes was also verified by immunohistochemistry in the Human Protein Atlas (HPA) database and transcription factor–hub gene regulatory network. Machine learning (ML) methods including data pre-processing, model selection and cross-validation, and performance evaluation were examined on the hub-gene expression profiles in five Gene Expression Omnibus datasets and verified on a GEO external validation (EV) dataset. Six supervised learning models (support vector machine, random forest, k-nearest neighbors, neural network, decision tree, and eXtreme Gradient Boosting) and one semi-supervised learning model (label spreading) were established to evaluate the diagnostic value of biomarkers. Among the six supervised models, the support vector machine (SVM) algorithm was the most effective one according to calculated performance metrics, including 0.93 and 0.99 area under the curve (AUC) scores on the test and external validation datasets, respectively. Furthermore, the semi-supervised model could also successfully learn and predict sample types, achieving a 0.986 AUC score on the EV dataset, even when 10% samples in the five GEO datasets were labeled. In conclusion, three hub genes (ATP4A, ATP4B, and ESRRG) closely related to gastric cancer were mined, based on which the ML diagnostic model of gastric cancer was conducted.

Abstract 5763: Comprehensive characteristics between genomic alterations and tumor differentiation in Chinese patients with colorectal cancer

Abstract Background: Colorectal cancer (CRC) is a malignant tumor that seriously threatens human health. Valuable diagnostic and prognostic biomarkers are urgently needed for colorectal cancer. We aim to analyze the mutational characteristics of Chinese CRC patients with different tumor differentiation degree, in order to improve the diagnosis and prognosis of this population. Methods: We retrospectively analyzed tumor tissue specimens from colorectal cancer patients who were treated at the First Affiliated Hospital of Shanxi Medical University from 2019 to 2021. Targeted NGS for 450 genes was performed in OrigiMed (Shanghai, China), a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: There were 35 males (55.6%) and 28 females (44.4%) with a median age of 60 (range 23-87) years were involved, including 55 moderately and well differentiated and 8 poorly differentiated colorectal tumors. The mutational frequency of BRAF in the poorly differentiated group was significantly higher than that in moderately and well differentiated group(25% vs. 1.8%, p=0.04). The mutational frequencies of the chromosome folding pathway, notch pathway, and PI3K pathway in poorly differentiated group were significantly lower than that in moderately and well differentiated group(p=0.975X10-15,p=0.97 X 10-26,and p=0.00517, respectively). In this study, the mutations of PDCD1 (programmed cell death 1) and TSC2 Significantly associated with tumor mutation burden (p=0.007 and p=0.047, respectively). In addition, high-frequency co-mutations of chromosome folding-related genes and DNA damage repair-related genes, such as co-mutations between ARID1A-MLH1,KMT2D-MSH6,KMT2D-MSH2, KMT2D-BRCA1, ARID1A-CHEK2, were detected in this study. Conclusions: We compared the genomic alterations between well-differentiated group and poorly-differentiated group in Chinese CRC patients. Our data showed significant differences in mutational frequency of chromosome folding pathways, notch pathways, and PI3K pathways between well-differentiated group and poorly-differentiated group. Meanwhile, we also identified the high-frequency and complex co-mutation characteristics of chromosome folding pathway genes and DNA damage repair genes in Chinese CRC patients. Citation Format: Xiaolong Cui, Aigang Ren, Hao Chen, Yaoliang Huo, Yanwu Zeng, Hao Zhang, Meizhen Hu, He Huang, Yuntong Guo. Comprehensive characteristics between genomic alterations and tumor differentiation in Chinese patients with colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5763.

Circular RNAs Hsa_circ_101555 and Hsa_circ_008068 as Diagnostic Biomarkers for Early-Stage Lung Adenocarcinoma.

BackgroundLung adenocarcinoma (LUAD) is a life-threatening disease worldwide with a high mortality rate. The early diagnosis of LUAD is crucial for improving subsequent treatment and prognosis. However, biomarkers for early detection remain a clinical challenge in LUAD. Here, we aimed to develop circular RNAs (circRNAs) in circulating plasma from LUAD patients as valuable diagnostic biomarkers in LUAD.MethodsCircRNA expression was determined by circRNA microarray in three pairs of LUAD tumour tissues and patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were selected as potential biomarkers in LUAD tissues and plasma by RT–PCR, respectively. The diagnostic value was analysed by the area under the curve (AUC) and the receiver operating characteristic (ROC) test.ResultsOur results showed that 6261 circRNAs were upregulated and 7238 circRNAs were downregulated in LUAD tumour tissues compared with patient-matched normal lung tissues. Hsa_circ_101555 and hsa_circ_008068 were filtered as biomarkers for early-stage LUAD. Q-PCR results showed that hsa_circ_101555 and hsa_circ_008068 were significantly upregulated in both LUAD cancer tissues and circulating plasma. Hsa_circ_101555 and hsa_circ_008068 were positively associated with tumour differentiation, tumour size and CEA (P<0.05). The ROC analysis showed that hsa_circ_101555 and hsa_circ_008068 had a better diagnostic potential compared to the traditional biomarkers (CEA, SCC, CYFRA21-1) in the detection of early-stage LUAD.ConclusionThe circular RNAs hsa_circ_101555 and hsa_circ_008068 could serve as novel diagnostic biomarkers for early-stage LUAD.

Mortality prediction of retinal vessel diameters and function in a long-term follow-up of haemodialysis patients.

Retinal vessel diameters are candidate biomarkers of mortality prediction in large population-based studies. We aimed to investigate the predictive value of retinal vessel diameters and flicker-induced retinal arteriolar and venular dilation on all-cause mortality in long-term follow-up of haemodialysis patients. Retinal vessel diameters as well as maximum arteriolar (aMax) and venular dilation (vMax) were investigated in 275 and 214 haemodialysis patients, respectively. Patients were observed in a long-term follow-up for a median period of 73 months. About 36% (76/214) and 41% (113/275) of patients died. Arteriolar and venular diameters were 175 ± 19 and 208 ± 20 µm, respectively. Median aMax and vMax were 1.6 (0.3-3.3) and 3.2 (2.0-5.1)%. Patients within the lowest tertile of vMax showed lower 5-year survival rates compared with the highest tertile (50.6 vs. 82.1%) and also exhibited a higher incidence of infection-related deaths (21.7 vs. 4.0%). Univariate hazard ratio (HR) per standard deviation increase of vMax for all-cause mortality was 0.69 (0.54-0.88) and was even more pronounced for infection-related mortality [HR 0.53 (0.33-0.83)]. Regarding all-cause mortality, multivariate adjustment for eight non-retinal mortality predictors including interleukin-6 did not attenuate the HR relevantly [0.73 (0.54-0.98)]. Arteriolar and venular diameters did not predict all-cause nor cardiovascular and infection-related mortality. Long-term follow-up of patients on haemodialysis demonstrated the potential of retinal venular dilation capacity for mortality prediction, which was most pronounced for infection-related mortality. In the same cohort, retinal arteriolar and venular diameters showed no predictive value for hard endpoints. Retinal venular dilation but not arteriolar and venular diameters is a valuable diagnostic biomarker for risk prediction in patients with end-stage renal disease and should be considered for monitoring of critically ill patients.

Quantitative proteomics in medication-related osteonecrosis of the jaw: A proof-of-concept study.

Medication-related osteonecrosis of the jaw (MRONJ) is a paradoxical effect associated with bone-modifying agents (BMAs) and other drugs. Currently, no valuable diagnostic or prognosis biomarkers exist. The goal of this research was to study MRONJ-related salivary proteome. This case-control aimed to study salivary proteome in MRONJ versus control groups (i) formed from BMAs consumers and (ii) healthy individuals to unravel biomarkers. Thirty-eight samples of unstimulated whole saliva (18MRONJ patients, 10 BMA consumers, and 10healthy controls) were collected. Proteomic analysis by SWATH-MS coupled with bioinformatics analysis was executed. A total of 586 proteins were identified, 175 proteins showed significant differences among MRONJ versus controls. SWATH-MS revealed differentially expressed proteins among three groups, which have never been isolated. These proteins had distinct roles including cell envelope organization, positive regulation of vesicle fusion, positive regulation of receptor binding, or regulation of low-density lipoprotein particle clearance. Integrative analysis prioritized 3 proteins (MMP9, AACT, and HBD). Under receiver-operating characteristic analysis, this panel discriminated MRONJ with a sensitivity of 90% and a specificity of 78.9%. These findings may inform a novel biomarker panel for MRONJ prediction or diagnosis. Nonetheless, further research is needed to validate this panel.

A Comprehensive Analysis of the Glutathione Peroxidase 8 (GPX8) in Human Cancer.

ObjectiveNowadays, cancer is still a leading public health problem all over the world. Several studies have reported the GPX8 could be correlated with the poor prognostic of Gastric Cancer and Breast Cancer. However, the prognostic potential of GPX8 in pan-cancer remains unclear. In this work, we aimed to explore the prognostic and immunological role of GPX8 in human cancer and confirm the oncogenic value in GBM.MethodsThe data of TCGA, CPTAC and GEO databases were adopted for the survival analysis. Based on the RNAseq and Methylation450 data of TCGA, the R language and package “ggplot2” were used to analyze the DNA methylation at the region of the promoter of GPX8 in tumors. The genetic alteration of GPX8 from TCGA cancers was investigated in cBioPortal. The R package “GSVA” and “ssGSEA” were employed to evaluate the correlation of GPX8 expression with the immune infiltration. The KEGG website was used for pathway analysis. The STRING website and GEPIA were performed to predict GPX8-binding proteins. The R package “ggplot2” and “clusterprofile” were used to analyze and visualize the GO and KEGG analysis. A normal human astrocyte cell line and three GBM cell lines were cultured under suitable conditions. The shRNA was transferred to cells by Lipofectamine 3000. The qRT-PCR and WB were adopted to detect the expression of GPX8. The wound-healing assay and transwell assay were taken to analyze the invasive and metastatic abilities. The tumor tissues and paracancerous ones were collected from patients with GBM. WB assay was employed to analyze the expression of GPX8 protein.ResultsGPX8 was a valuable diagnostic biomarker in multiple cancers, including GBM/LGG (glioblastoma multiforme/Brain lower grade glioma), KIRC (kidney renal clear cell carcinoma), KIRP (kidney renal papillary cell carcinoma) and STAD (stomach adenocarcinoma). Moreover, we observed a correlation between the expression of GPX8 and the reduced DNA methylation at the promoter region in several tumors, such as GBM/LGG. Our results indicated a positive correlation between the GPX8 expression and immune infiltration. In addition, the enrichment analysis demonstrated that antioxidant activity was mainly involved in the functional mechanism of GPX8. In particular, we first confirmed the up-regulated of GPX8 in GBM cells and observed the suppression of migrative and invasive phenotypes by knockdown of GPX8. Furthermore, we confirmed the expression of GPX8 was higher in GBM tumor tissues than paracancerous ones.ConclusionOur study showed a correlation of GPX8 expression with clinical prognosis, DNA methylation and immune infiltrates. Furthermore, we first confirmed GPX8 was highly expressed in GBM cells and contributed to migration and invasion. These results provided a predictive biomarker and an inclusive understanding of the GPX8 expression in multiple tumors types, especially in GBM.

Machine-Learning Algorithm-Based Prediction of Diagnostic Gene Biomarkers Related to Immune Infiltration in Patients With Chronic Obstructive Pulmonary Disease.

ObjectiveThis study aims to identify clinically relevant diagnostic biomarkers in chronic obstructive pulmonary disease (COPD) while exploring how immune cell infiltration contributes towards COPD pathogenesis.MethodsThe GEO database provided two human COPD gene expression datasets (GSE38974 and GSE76925; n=134) along with the relevant controls (n=49) for differentially expressed gene (DEG) analyses. Candidate biomarkers were identified using the support vector machine recursive feature elimination (SVM-RFE) analysis and the LASSO regression model. The discriminatory ability was determined using the area under the receiver operating characteristic curve (AUC) values. These candidate biomarkers were characterized in the GSE106986 dataset (14 COPD patients and 5 controls) in terms of their respective diagnostic values and expression levels. The CIBERSORT program was used to estimate patterns of tissue infiltration of 22 types of immune cells. Furthermore, the in vivo and in vitro model of COPD was established using cigarette smoke extract (CSE) to validated the bioinformatics results.Results80 genes were identified via DEG analysis that were primarily involved in cellular amino acid and metabolic processes, regulation of telomerase activity and phagocytosis, antigen processing and MHC class I-mediated peptide antigen presentation, and other biological processes. LASSO and SVM-RFE were used to further characterize the candidate diagnostic markers for COPD, SLC27A3, and STAU1. SLC27A3 and STAU1 were found to be diagnostic markers of COPD in the metadata cohort (AUC=0.734, AUC=0.745). Their relevance in COPD were validated in the GSE106986 dataset (AUC=0.900 AUC=0.971). Subsequent analysis of immune cell infiltration discovered an association between SLC27A3 and STAU1 with resting NK cells, plasma cells, eosinophils, activated mast cells, memory B cells, CD8+, CD4+, and helper follicular T-cells. The expressions of SLC27A3 and STAU1 were upregulated in COPD models both in vivo and in vitro. Immune infiltration activation was observed in COPD models, accompanied by the enhanced expression of SLC27A3 and STAU1. Whereas, the knockdown of SLC27A3 or STAU1 attenuated the effect of CSE on BEAS-2B cells.ConclusionSTUA1 and SLC27A3 are valuable diagnostic biomarkers of COPD. COPD pathogenesis is heavily influenced by patterns of immune cell infiltration. This study provides a molecular biology insight into COPD occurrence and in exploring new therapeutic means useful in COPD.

Relationship Between Serum Concentration of Adrenomedullin and Myocardial Ischemic T Wave Changes in Patients With Lung Cancer.

BackgroundPatients with lung cancer are at increased risk for the development of cardiovascular diseases. Molecular markers for early diagnosis of cardiac ischemia are of great significance for the early prevention of cardiovascular events in patients with lung cancer. By evaluating the relationship between adrenomedullin (ADM) and myocardial ischemic T wave changes, the clinical value of circulating ADM as a predictor of myocardial ischemia in patients with lung cancer is confirmed.MethodsWe enrolled patients with lung cancer and healthy people from 2019 to 2021 and extracted a detailed ECG parameter. After adjustment for potential confounders, logistic regression was used to assess the association of clinical data. We performed analyses on differences in T wave between patients with lung cancer and healthy people, and the relationship between T wave and ADM among patients with lung cancer. Receiver operator characteristic (ROC) curves were drawn to confirm the diagnostic value of biomarkers.ResultsAfter adjusting for potential confounders, the incidence of T wave inversion or flattening in patients with lung cancer was higher than in healthy people (OR: 3.3228, P = 0.02). Also, further analysis of the data of lung cancer patients revealed that the ADM in lung cancer patients with T wave inversion or flat was higher than those with normal T wave (189.8 ± 51.9 vs. 131.9 ± 38.4, p < 0.001). The area under the ROC curve was 0.8137.ConclusionAmong the patients with lung cancer, serum ADM concentration is associated with the incidence of the abnormal T wave. ADM might be a potentially valuable predictor for heart ischemia in patients with lung cancer.

Evaluation of the Prognostic Relevance of Differential Claudin Gene Expression Highlights Claudin-4 as Being Suppressed by TGFβ1 Inhibitor in Colorectal Cancer.

Background: Claudins (CLDNs) are a family of closely related transmembrane proteins that have been linked to oncogenic transformation and metastasis across a range of cancers, suggesting that they may be valuable diagnostic and/or prognostic biomarkers that can be used to evaluate patient outcomes. However, CLDN expression patterns associated with colorectal cancer (CRC) remain to be defined. Methods: The mRNA levels of 21 different CLDN family genes were assessed across 20 tumor types using the Oncomine database. Correlations between these genes and patient clinical outcomes, immune cell infiltration, clinicopathological staging, lymph node metastasis, and mutational status were analyzed using the GEPIA, UALCAN, Human Protein Atlas, Tumor Immune Estimation Resource, STRING, Genenetwork, cBioportal, and DAVID databases in an effort to clarify the potential functional roles of different CLDN protein in CRC. Molecular docking analyses were used to probe potential interactions between CLDN4 and TGFβ1. Levels of CLDN4 and CLDN11 mRNA expression in clinical CRC patient samples and in the HT29 and HCT116 cell lines were assessed via qPCR. CLDN4 expression levels in these 2 cell lines were additionally assessed following TGFβ1 inhibitor treatment. Results: These analyses revealed that COAD and READ tissues exhibited the upregulation of CLDN1, CLDN2, CLDN3, CLDN4, CLDN7, and CLDN12 as well as the downregulation of CLDN5 and CLDN11 relative to control tissues. Higher CLDN11 and CLDN14 expression as well as lower CLDN23 mRNA levels were associated with poorer overall survival (OS) outcomes. Moreover, CLDN2 and CLDN3 or CLDN11 mRNA levels were significantly associated with lymph node metastatic progression in COAD or READ lower in COAD and READ tissues. A positive correlation between the expression of CLDN11 and predicted macrophage, dendritic cell, and CD4+ T cell infiltration was identified in CRC, with CLDN12 expression further being positively correlated with CD4+ T cell infiltration whereas a negative correlation was observed between such infiltration and the expression of CLDN3 and CLDN15. A positive correlation between CLDN1, CLDN16, and neutrophil infiltration was additionally detected, whereas neutrophil levels were negatively correlated with the expression of CLDN3 and CLDN15. Molecular docking suggested that CLDN4 was able to directly bind via hydrogen bond with TGFβ1. Relative to paracancerous tissues, clinical CRC tumor tissue samples exhibited CLDN4 and CLDN11 upregulation and downregulation, respectively. LY364947 was able to suppress the expression of CLDN4 in both the HT29 and HCT116 cell lines. Conclusion: Together, these results suggest that the expression of different CLDN family genes is closely associated with CRC tumor clinicopathological staging and immune cell infiltration. Moreover, CLDN4 expression is closely associated with TGFβ1 in CRC, suggesting that it and other CLDN family members may represent viable targets for antitumor therapeutic intervention.

Phosphorylated neurofilament heavy chain: a potential diagnostic biomarker in amyotrophic lateral sclerosis.

Neuroaxonal damage is a feature of various neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Phosphorylated neurofilament heavy chain (pNfH) is a cytoskeletal structural protein released as a result of axonal damage into the cerebrospinal fluid (CSF), and subsequently into the blood. Due to high specificity for neuronal cell damage, pNfH is advantageous over other biomarkers, for ALS disease identification. Here, we review the structure and function of neurofilaments and their role in detection of various neurodegenerative conditions. In addition, a retrospective meta-analysis was performed to depict the significance of pNfH as a valuable diagnostic and prognostic biomarker in ALS.

Comprehensive Analysis of Sinonasal Inverted Papilloma Expression Profiles Identifies Long Non-Coding RNA AKTIP as a Potential Biomarker.

Long noncoding RNAs (lncRNAs) are a novel class of potential biomarkers and therapeutic targets for the treatment of neoplasms. The purpose of this study was to explore the expression profile, potential functions, and diagnostic and clinical significance of lncRNAs in sinonasal inverted papilloma (SNIP). The expression profiles of lncRNAs and mRNAs were analyzed using a microarray. The potential functions and clinical implications of specific lncRNAs were further analyzed by bioinformatics and statistical methods. Microarray analysis identified 1,668 significantly upregulated and 1,767 downregulated lncRNAs in SNIP. Several mRNAs coexpressed with lncRNAs were enriched in some biological processes and cellular signaling pathways related to tumorigenesis. Lnc-AKTIP might interact with a variety of tumor-associated proteins and transcription factors, such as PCBP2, IRF-1, and p53. Receiver operating characteristic curve analysis for lnc-AKTIP showed an area under the curve of 0.939. Notably, its expression level was significantly decreased in SNIP tissues versus normal tissues and was associated with SNIP staging. Lnc-AKTIP may serve as a valuable diagnostic biomarker and a therapeutic target for SNIP.

A ratiometric fluorescent nanoprobe for signal amplification monitoring of intracellular telomerase activity.

Telomerase is considered a valuable diagnostic and prognostic cancer biomarker. Accurate and reliable detection of telomerase activity is of great value in clinical diagnosis, screening of inhibitors, and therapeutics. Here, we developed a novel amplified fluorescence resonance energy transfer (FRET) nanoprobe for highly sensitive and reliable monitoring of intracellular telomerase activity. The nanoprobe (QDSA@DNA) was composed of a streptavidin-modified quantum dot (QDSA) which was functionalized with a telomerase primer sequence (TP) and Cy5-tagged signal switching sequence (SS) through biotin-streptavidin interaction. When the nanoprobe was assembled, the Cy5 was in close proximity to the QDSA, resulting in high FRET efficiency from the QDSA to Cy5. In the presence of telomerase, the TP could be extended to produce telomeric repeat units, which was complementary to the loop of SS. Thus, the SS could hybridize with elongated sequences to form a rigid double-stranded structure, which forced the Cy5 away from the surface of the QDSA, causing low FRET efficiency. Furthermore, due to the production of multiple repeat units by telomerase, multiple hairpin structures could be opened, yielding significant fluorescence ratio (FQDsa/FCy5) enhancement for sensing of telomerase activity. In this way, the combination of a FRET and target-assisted strategy in a nanoprobe improved the detection accuracy and amplified the detection signal, respectively. The QDSA@DNA nanoprobe also showed high selectivity, excellent nuclease stability, and good biocompatibility. More importantly, this nanoprobe was found to be an excellent platform for efficient monitoring of intracellular telomerase activity, providing a potential platform in tumor diagnosis and screening of telomerase-related inhibitors.

Epigenetic inactivation of ACAT1 promotes epithelial-mesenchymal transition of clear cell renal cell carcinoma.

Acetyl-CoA acyltransferase 1 (ACAT1) is a key enzyme catalyzing the production of mitochondrial ketone bodies. We have shown that ACAT1 is down-regulated in kidney renal clear cell carcinoma (KIRC) previously. To investigate the reasons for downregulation of ACAT1 in KIRC and explore the underlying mechanisms involved in metastatic inhibition regulated by ACAT1. The Gene Expression Omnibus (GEO) database was queried for meta-analysis of ACAT1 mRNA expression in KIRC. The UALCAN website was used to compare the methylation levels of the ACAT1 promoter region in KIRC and normal tissues. RT-qPCR was used to quantitate ACAT1 transcription levels. The GCBI and Tarbase V.8 databases were used to predict miRNAs that may target the mRNA of ACAT1. The correlation between mRNA expression of ACAT1, MMP7 (matrix metallopeptidase 7), CDH1 (E-cadherin), EpCAM (epithelial cell adhesion molecule), and VIM (vimentin) was analyzed. Extracellular MMP7 protein was quantitated using an ELISA assay. The methylation level of the ACAT1 promoter region in KIRC was significantly higher than that in the normal kidney tissues. The ACAT1 mRNA expression in the KIRC cell lines was restored after treatment with 5-aza-dC (p < 0.05). MiR-21-5p is a conserved microRNA targeting ACAT1. It is expressed at a significantly higher level in KIRC than in normal tissues (p < 0.001). MiR-21-5p miRNA expression negatively correlates with ACAT1 mRNA expression. The expression of miR-21-5p is higher at the T3-T4 stages and in the histologic grades G3-G4. Patients with high miR-21-5p expression tended to have lower overall survival, suggesting that miR-21-5p could serve as a potentially valuable diagnostic biomarker for KIRC (AUC = 0.957; p < 0.001). A mimetic of miR-21-5p inhibited the expression of ACAT1 mRNA and protein. In addition, ACAT1 mRNA expression positively correlates with CDH1 and EpCAM but is negatively correlated with VIM. Overexpression of ACAT1 suppresses the secretion of MMP7 in KIRC cells. Expression of ACAT1 in KIRC is controlled at two levels, firstly by the hypermethylation of the ACAT1 promoter region and secondly by overexpression of miR-21-5p. Downregulation of ACAT1 expression correlates with epithelial-mesenchymal transition (EMT).

Diagnostic performance of miR-21, miR-124, miR-132, and miR-200b serums in post-stroke cognitive impairment patients.

The diagnosis of post-stroke cognitive impairment (PSCI) mainly depends on neuro-psychological evaluation. It still lacks a sensitive and objective diagnostic biomarker. MicroRNAs (miRNAs, miRs) are novel and potential disease biomarkers. Our aim was to detect which specific miRNA is a good diagnostic biomarker for PSCI. There were 77 first-ever stroke patients enrolled. Blood samples were collected at 14 days after stroke. Level of serum miR-21, miR-124, miR-132, and miR-200b were determined by quantitative polymerase chain reaction. Mini-mental state examination (MMSE) scale was used to measure the cognitive function of patients. Factional anisotropy (FA) score of diffusion tensor imaging was applied to detect the alteration of white matter. In addition, the relationship between miRNA level and cognitive status was further explored by correlation analysis. Finally, 45 PSCI and 32 post-stroke cognitive normality (PSCN) patients were enrolled. The expression of miR-21, miR-132, and miR-200b in PSCI patients was higher than in PSCN patients. In particular, the miR-21 level was substantially correlated with MMSE scores (r = 0.752, p < 0.001) and FA value (r = 0.636, p < 0.001). Additionally, the diagnostic performance of miR-21 alone or the combination of miR-21 and FA values performed well. The miR-21 alone or combination of miR-21 and FA values are valuable diagnostic biomarkers in discriminating PSCI from PSCN.

Has_Circ_0002490 Circular RNA: A Potential Novel Biomarker for Lung Cancer.

Background: Lung cancer (LC) is ranked as a leading cause of cancer-related death worldwide. However, there are still few reliable screening biomarkers for daily clinical practice in LC. Circular RNAs (circRNAs) have been suggested as valuable diagnostic biomarkers in various cancers. In this study, the expression and diagnostic potential of several circRNAs for LC were explored. Methods: Seventy-two pairs of LC tissues and adjacent normal lung tissues were collected to measure the relative expression level of circRNAs using quantitative reverse transcription-polymerase chain reaction. In addition, the relationships between circRNAs and the clinicopathological features of LC patients were analyzed. Furthermore, the sensitivities and specificities of the circRNAs were evaluated by receiver operating characteristic (ROC) analysis. Results: The expression levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, has_circ_0074368, and has_circ_0000896 were downregulated in LC tissues compared with adjacent normal lung tissues. The lower levels of has_circ_0002490, has_circ_0087357, has_circ_0004891, and has_circ_0000896 were significantly correlated with advanced disease stages. The area under the ROC curves of has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 were 0.833, 0.793, 0.773, 0.730, and 0.645, respectively. Conclusions: Has_circ_0002490, has_circ_0087357, has_circ_0074368, has_circ_0004891, and has_circ_0000896 are capable of distinguishing LC tissues from normal lung tissues. Besides, the biggest area under the ROC curve value of has_circ_000249 suggests it appears to be a better diagnosis marker for LC patients.

Serum level of Total Antioxidant Status and Malondialdehyde in the Patients with Polycystic Ovarian Syndrome: a Comparative Study

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder in women of reproductive age and a major cause of infertility. Anti- Mullerian Hormone (AMH), a valid marker of ovarian function, is used for the diagnosis of PCOS. The aim of this study is to assess the serum level of total antioxidant status (TAS) and malondialdehyde (MDA) in the premenopausal women with PCOS. &#x0D; Methods: A cross-sectional analytical study was conducted at Padmashree Diagnostics, Department of Gynecology, India from April 2016 to March 2017. Census method was used to select the samples. The oxidative stress was measured by measuring the level of TAS and MDA. The data was recorded in structured proforma and and enter in SPSS version 16.0. The data were expressed in frequency, percentage, mean and standard deviation and the results obtained were analyzed using pearson’s correlation and student’s t-test. The p-value less than 0.05 was taken as statistically significant.&#x0D; Results: The measured serum AMH level among the patients with PCOS was within normal range in 67.5% (27) and above normal range in 32.5% (13). The serum TAS level in normal AMH group was 814.0 + 291 µMol/L and in above normal range group was 720 + 240 µMol/L, (p &lt;0.001). Similarly, the serum level of MDA in normal AMH group was 6.64 + 0.21 µMol/L, and in above normal range group was 8.78 + 0.22 µMol/L (p = 0.01). The measured level of AMH was significantly associated with the increased level of MDA (p&lt;0.001) and decreased level of TAS (p&lt;0.001). The measured MDA level in high AMH group did show statistically significant than the normal AMH group.&#x0D; Conclusions: Serum level of TAS and MDA along with AMH are valuable diagnostic biomarker for the diagnosis of PCOS in the resource poor settings where ultrasound facility is unavailable.