The latest medical research on Clinical Paediatric Genetics

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about clinical paediatric genetics gathered by our medical AI research bot.

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Prognostic score model based on six m6A-related autophagy genes for predicting survival in esophageal squamous cell carcinoma.

Clinical Laboratory

Prognostic signatures based on autophagy genes have been proposed for esophageal squamous cell carcinoma (ESCC). Autophagy genes are closely associated with m6A genes. Our purpose is to identify m6A-related autophagy genes in ESCC and develop a survival prediction model.

Differential expression analyses for m6A genes and autophagy genes were performed based on TCGA and HADd databases followed by constructing a co-expression network. Uni-variable Cox regression analysis was performed for m6A-related autophagy genes. Using the optimal combination of feature genes by LASSO Cox regression model, a prognostic score (PS) model was developed and subsequently validated in an independent dataset.

The differential expression of 13 m6A genes and 107 autophagy genes was observed between ESCC and normal samples. The co-expression network contained 13 m6A genes and 96 autophagy genes. Of the 12 m6A-related autophagy genes that were significantly related to survival, DAPK2, DIRAS3, EIF2AK3, ITPR1, MAP1LC3C, and TP53 were used to construct a PS model, which split the training set into two risk groups with significant different survival ratios (p = 0.015, 1-year, 3-year, and 5-year AUC = 0.873, 0.840, and 0.829). Consistent results of GSE53625 dataset confirmed predictive ability of the model (p = 0.024, 1-year, 3-year, and 5-year AUC = 0.793, 0.751, and 0.744). The six-gene PS score was an independent prognostic factor from clinical factors (HR, 2.362; 95% CI, 1.390-7.064; p-value = 0.012).

Our study recommends 6 m6A-related autophagy genes as promising prognostic biomarkers and develops a PS model to predict survival in ESCC.

Diagnostic and prognostic value of circRNAs expression in head and neck squamous cell carcinoma: A meta-analysis.

Clinical Laboratory

Circular RNAs (circRNAs) have been found to have potential biological applications against tumors in humans. This study aimed to evaluate the diagnostic, prognostic, and clinicopathological value of circRNAs in head and neck squamous cell carcinoma (HNSCC).

The PubMed, Web of Science, EMBASE, and the Cochrane Library were comprehensively searched for the relevant studies before October 20, 2021. Statistical analysis was performed based on STATA 15.0, Meta-DiSc 1.4, and RevMan 5.3 software.

A total of 55 reports regarding 56 kinds of circRNA were studied in this meta-analysis, including 23, 38, and 26 articles on diagnosis, prognosis, and clinicopathological features, respectively. The pooled sensitivity, specificity, and area under the curve (AUC) of the summary receiver-operating characteristic curve (SROC) were 0.78, 0.84, and 0.87, respectively. Besides, the upregulation of oncogenic circRNAs was significantly associated with poorer overall survival (OS) (HR=2.25, p < 0.05) and disease-free interval (DFS) (HR=1.92, p < 0.05). In contrast, the elevated expression of tumor suppressor circRNAs was associated with a favorable prognosis (HR=0.50, p < 0.05). In addition, the high expression of oncogenic circRNAs was associated with the tumor size (OR=3.59, p < 0.05), degree of differentiation (OR=1.89, p < 0.05), TNM stage (OR=2.35, p < 0.05), lymph node metastasis (OR=1.85, p < 0.05), and distant metastasis (OR=3.42, p < 0.05). Moreover, the expression of tumor suppressor circRNAs was associated with improved clinicopathological features (lymph node metastasis: OR=0.25, p < 0.05).

CircRNAs could serve as potential predictive indicators and be useful for the diagnosis, prognosis, and identification of clinicopathological features in HNSCC.

Analytical performances of a glycated albumin assay that is traceable to standard reference materials and reference range determination.

Clinical Laboratory

Glycated albumin (GA) is an intermediate-term marker for monitoring glycemic control (preceding 2-3 weeks) in patients with diabetes mellitus. We evaluated the performance of Lucica Glycated Albumin-L, a new GA assay that is traceable to standard reference materials and determined the reference range in healthy subjects without diabetes.

The performance and reference range studies were conducted in accordance with Clinical and Laboratory Standards Institute (CLSI) Guidelines. The traceability was established using reference material recommended by the Japan Society of Clinical Chemistry (JSCC).

The coefficient of variation (CV) of overall repeatability, within-laboratory precision, and overall reproducibility values of GA values were not more than 2.6%, 3.3%, and 1.6%, respectively, among laboratories. The GA values showed good linearity from 173 to 979 mmol/mol (9.4%-54.9%) across the assay range. The GA reference range in 262 healthy subjects was between 183 and 259 mmol/mol (9.9%-14.2%) while that of subjects with diabetes was 217-585 mmol/mol (11.8-32.6%). The reagent was stable for 2 months on the bench at room temperature. The limits of blank, detection, and qualification were 6.9, 7.9, and 9.7 μmol/L for GA concentration, and 3.8, 7.0, and 21.8 μmol/L for albumin concentration, respectively. Hemoglobin slightly affected the assay, while other classical interfering substances had no significant impact.

The present GA assay shows comparable performance to current clinical assays and could be used for intermediate-term monitoring of glycemic control in diabetes patients.

Efficacy of autoantibodies combined with tumor markers in the detection of lung cancer.

Clinical Laboratory

The purpose of this study was to explore the detection value of seven autoantibodies (TAAbs): p53, PGP9.5, SOX2, GBU4-5, MAGE A1, CAGE, and GAGE7 and three tumor markers: CYFRA21-1, NSE, and SCCA in the diagnosis of lung cancer.

ELISA was used to detect the levels of the TAAbs, and chemiluminescence immunoassay was used to test the levels of the tumor markers. The diagnostic efficacy of the TAAbs combined with the tumor markers for lung cancer was evaluated by receiver operating characteristic (ROC) curves.

The positive rate of the combined detection of seven TAAbs and three tumor markers in lung cancer (37.8%) was higher than that in other three groups. The positive rates of SOX2, GAGE7, MAGE A1, CAGE, CYFRA21-1, and SCCA had differences among the four groups. Compared with the benign lung disease group, only GAGE7, CYFRA21-1, and SCCA differed among the groups. The combined sensitivity of the TAAbs was 29.07% (AUC, 0.594), the combined sensitivity of all the markers was 37.76% (AUC, 0.660 [p < 0.05]), and Youden's index was 0.196. In the lung cancer group, CYFRA21-1 had a significant difference in age and sex, and SOX2, MAGE A1, CYFRA21-1, NSE, and SCCA were significantly different in pathological type and TNM. In contrast, p53 and GBU4-5 showed no significant differences in age, sex, pathological type, and TNM.

The combined detection of seven TAAbs and three tumor markers could be useful in early diagnosis of lung cancer.

Analysis of current status of quantitative detection of biomarkers for liver fibrosis in Clinical labs in China.

Clinical Laboratory

To explore the quality control and implementation of the quantitative detection of liver fibrosis biomarkers, laminin (LN), collagen IV (Col Ⅳ), procollagen III amino-terminal propeptide (PⅢNP), hyaluronic acid (HA), and cholyglycine (CG), in China.

Two quality control products were measured in different laboratories using different measurement methods and reagents, and the acquired results were subjected to analysis. The quantitative detection technique was based on the conventional assessment criteria, with a target value ±30% being employed.

Hundred labs were involved in the External Quality Assessment with 88 laboratories completing the assessment, and the pass rates were 84%, 80.2%, 67.5%, 77.3%, and 58.3% for HA, LN, PⅢNP, Col Ⅳ, and CG, respectively. Chemiluminescence immunoassay was used most for HA (90.1%), LN (90.1%), PⅢNP (87.9%), and Col Ⅳ (82.9%) determination, whereas the chemiluminescence immunoassay (31.6%), latex-enhanced immunoturbidimetry (36.7%), and homogeneous enzyme immunoassay (26.7%) were used for CG determination. The coefficients of variation for HA, LN, PⅢNP, Col Ⅳ, and CG in different laboratories were 3.3%-19.49%, 1.74%-38.81%, 1.97%-41.29%, 2.85%-41.69%, and 2.71%-41.8%, respectively.

The clinical quantitative detection of liver fibrosis biomarkers is highly performed in China. The existing problems are that there are many manufacturers producing reagents and instruments, the quality of reagents is uneven, the specificity and sensitivity of reagents are greatly different, the comparability of results of various systems is poor, and the accuracy and consistency between different systems are lacking. All above underscores the critical importance of EQA in improving and monitoring the identification of biomarkers for liver fibrosis.

A novel four-gene signature predicts immunotherapy response of patients with different cancers.

Clinical Laboratory

Immune checkpoint blockade (ICB) therapy has demonstrated favorable clinical efficacy, particularly for advanced or difficult-to-treat cancer types. However, this therapy is ineffective for many patients displaying lack of immune response or resistance to ICB. This study aimed to establish a novel four-gene signature (CD8A, CD8B, TCF7, and LEF1) to provide a prognostic immunotherapy biomarker for different cancers.

Transcriptome profiles and clinical data were obtained from The Cancer Genome Atlas database. Multivariate Cox regression analysis was used to establish a four-gene signature. The R package estimate was used to obtain the immune score for every patient.

Risk scores of the novel four-gene signature could effectively divided all patients into high- and low-risk groups, with distinct outcomes. The immune score calculated via the estimate package demonstrated that the four-gene signature was significantly associated with the immune infiltration level. Furthermore, the four-gene signature could predict the response to atezolizumab immunotherapy in patients with metastatic urothelial cancer.

The novel four-gene signature developed in this study is a good prognostic biomarker, as it could identify many kinds of patients with cancer who are likely to respond to and benefit from immunotherapy.

LINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway.

Clinical Laboratory

LINC00941 has been proved to be related to various tumors, but its relationship with laryngocarcinoma remains vague.

LINC00941 expression in laryngocarcinoma tumor and laryngocarcinoma cells was determined by real time-quantitative polymerase chain reaction (RT-qPCR). Besides, the five-year survival of laryngocarcinoma patients with different LINC00941 expression was analyzed with Kaplan-Meier survival analysis, and the clinical characteristics of laryngocarcinoma patients were also recorded. After transfection, cell viability, cell proliferation, apoptosis, cell cycle, migration, and invasion were detected by cell counting kit-8 (CCK-8), colony formation, flow cytometry, cell scratch, and Transwell assays, respectively. Glycolysis was assessed by the colorimetric method. Expressions of proliferation-associated proteins, migration-associated proteins, glycolysis-associated proteins, and phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signal pathway-associated proteins were detected by Western blot.

In laryngocarcinoma tumor tissues and cells, LINC00941 was highly expressed. High expression of LINC00941 decreased the 5-year survival of laryngocarcinoma patients, and it was positively related to lymph node metastasis and clinical stages. LINC00941 overexpression decreased apoptosis but promoted cell viability, proliferation, cell-cycle progression, migration, and invasion, and glucose consumption and lactate production in laryngocarcinoma cells. Moreover, LINC00941 overexpression elevated expressions of Ki-67, PCNA, MMP2, N-Cadherin, HK2, PFKFB4, and PKM, activated the PI3K/AKT/mTOR signal pathway but reduced E-Cadherin expression, while LINC00941 silencing had the opposite effects. PKM overexpression reversed the effects of LINC00941 silencing on cellular and glycolytic phenotypes.

LINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma cells by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway.

LncRNA PITPNA-AS1/miR-223-3p/PTN axis regulates malignant progression and stemness in lung squamous cell carcinoma.

Clinical Laboratory

Long noncoding RNAs (lncRNAs) are a kind of molecule that cannot code proteins, and their expression is dysregulated in diversified cancers. LncRNA PITPNA-AS1 has been shown to act as a tumor promoter in a variety of malignancies, but its function and regulatory mechanisms in lung squamous cell carcinoma (LUSC) are yet unknown.

The mRNA and protein expression of genes were examined by RT-qPCR, western blot, and IHC assay. The cell proliferation, migration, invasion, and stemness were detected through CCK-8, colony formation, Transwell and spheroid formation assays. The CD44+ and CD166+ -positive cells were detected through flow cytometry. The binding ability among genes through luciferase reporter and RNA pull-down assays. The tumor growth was detected through in vivo nude mice assay.

The lncRNA PITPNA-AS1 had increased expression in LUSC and was linked to a poor prognosis. In LUSC, PITPNA-AS1 also enhanced cell proliferation, migration, invasion, and stemness. This mechanistic investigation showed that PITPNA-AS1 absorbed miR-223-3p and that miR-223-3p targeted PTN. MiR-223-3p inhibition or PTN overexpression might reverse the inhibitory effects of PITPNA-AS1 suppression on LUSC progression, as demonstrated by rescue experiments. In addition, the PITPNA-AS1/miR-223-3p/PTN axis accelerated tumor development in vivo.

It is the first time we investigated the potential role and ceRNA regulatory mechanism of PITPNA-AS1 in LUSC. The data disclosed that PITPNA-AS1 upregulated PTN through sponging miR-223-3p to enhance the onset and progression of LUSC. These findings suggested the ceRNA axis may serve as a promising therapeutic biomarker for LUSC patients.

The preventive effects of different doses of atorvastatin on contrast-induced acute kidney injury after CT perfusion.

Clinical Laboratory

Contrast-induced acute kidney injury (CI-AKI) is a severe complication among patients receiving intravascular contrast media. The purpose of this study was to investigate the preventive effects of pretreatment of atorvastatin at intensive doses on CI-AKI after computed tomography (CT) perfusion.

The levels of serum creatinine (SCR), blood urea nitrogen (BUN), Cystatin C (CysC), estimated glomerular filtration rate (eGFR), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) in patients were compared between the observation group receiving 40 mg/kg atorvastatin and the control group receiving 20 mg/kg atorvastatin before and 72 h after CT examination. In addition, the incidence of CI-AKI was recorded.

Compared with the control group, the incidence of renal injury in the observation group was significantly reduced, from 8% to 2% (χ2  = 6.62, p = 0.010). In addition, there was no notable difference in the levels of Scr, BUN, CysC, hs-CRP, and IL-6 before CT examination between two groups (p > 0.05). The levels of SCR, BUN, CysC, hs-CRP, and IL-6 were increased, while the levels of eGFR were decreased in the control group at 72 h after CT examination (p < 0.05). At 72 h after CT enhancement, the levels of BUN, CysC, and hs-CRP were prominently increased in the observation group (p < 0.05), while SCR, eGFR, and IL-6 did not change (p > 0.05). Compared with the control group, the levels of SCR, BUN, CysC, eGFR, hs-CRP, and IL-6 in the observation group were significantly decreased at 72 h after CT examination (p < 0.05).

Intensive dose of atorvastatin pretreatment can prevent CI-AKI undergoing CT perfusion through lowering inflammation as well as renal function indexes SCR, CysC, BUN, and eGFR.

Safety evaluation of mutagenicity, genotoxicity, and cytotoxicity of Lactobacillus spp. isolates as probiotic candidates.

Clinical Laboratory

Probiotics promote a healthy balance of gut bacteria and have many beneficial effects on human digestive physiology. Although, few side effects of probiotics have been reported. This study aimed to assess the safety of five probiotic candidate Lactobacillus strains isolated from healthy individuals by examining mutagenicity, genotoxicity, and oral toxic effects.

Five selected candidate probiotic (SCPs) strains were evaluated for genotoxicity (Ames test with Salmonella typhimurium), in vitro mammalian chromosome aberration test and an in vivo mouse micronucleus assay on peripheral blood of mice. To evaluate the oral dose toxicity, BALB/c mice models were treated repeatedly (2000, 1000, and 500 mg/kg body weight /day) for 28-days.

The Ames test performed for two S. typhimurium strains TA 98 and TA100 (both in the absence and in the presence of S-9 metabolic activation system) did not show an increase in reverse mutation because of exposure to the SCPs in any of the doses (5.0, 2.5, 1.25, 0.625, and 0.3125 mg/plate). There was no genotoxicity in the SCPs treatment in the vitro chromosome aberration assay with Chinese hamster ovary cells (CHO-K1). In addition, none of the tested strains increased the frequency of micronucleated reticulocytes in reticulocytes, the SCPs with the studied doses caused no substantial variation in the experimental groups compared to the negative control group (p > 0.05). SCPs were not acutely toxic when administered to male and female BALB/c mice by single gavage at (2000, 1000, and 500 mg/kg b.w/day) with no mortality or clinical signs, change in body weight or macroscopic abnormalities were observed in this dose range.

As a result, SCPs did not induce mutagenic potential in vitro with bacterial reverse mutation, clastogenicity, and in vivo tests in the ranges of concentrations evaluated in our study.

Hsa_circ_0001982 promotes the proliferation, invasion, and multidrug resistance of osteosarcoma cells.

Clinical Laboratory

Osteosarcoma (OS) is the most common bone cancer mostly seen in people aged 10-25 years. This research aims to clarify the function of hsa_circ_0001982 in osteosarcoma (OS) and its effect on drug resistance, preliminarily exploring its mechanism.

The expression of hsa_circ_0001982 and miR-143 in OS clinical tissues and cells was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), MTT, colony formation assay, and transwell assay assessed cell proliferation, colony formation, migration, and invasion, respectively. The targeted relationship of hsa_circ_0001982 and miR-143 was verified by a dual-luciferase reporter assay.

The expression of hsa_circ_0001982 was significantly increased in OS tissues and cells (MG63), as in well as chemoresistant OS tissues and cells (MG63/Dox). Overexpression of hsa_circ_0001982 promoted proliferation, colony formation, migration, invasion, and multidrug resistance in MG63 cells. By contrast, knockdown of hsa_circ_0001982 markedly reduced the resistance of MG63/Dox cells to doxorubicin (IC50 evidently reduced). Bioinformatic prediction showed that miR-143 was a target miRNA of hsa_circ_0001982, and a dual-luciferase reporter assay proved this. Further experiments revealed that miR-143 expression was notably downregulated in OS tissues, chemoresistant OS tissues, and MG63/Dox cells. Moreover, miR-143 was negatively correlated with hsa_circ_0001982 in OS cells and tissues.

The regulation of malignant behaviors such as proliferation, invasion, migration, and multidrug resistance of OS cells by hsa_circ_0001982 may be achieved by targeting miR-143. Moreover, hsa_circ_0001982 is a potential target for early diagnosis and targeted therapy of OS.

Serum transfer RNA-derived fragment tRF-31-79MP9P9NH57SD acts as a novel diagnostic biomarker for non-small cell lung cancer.

Clinical Laboratory

tRNA-derived fragments (tRFs) have been found to have a crucial function in the pathophysiology of cancers. However, the function of tRFs in non-small cell lung cancer (NSCLC) is yet unknown. The goal of this study was to assess the tRF-31-79MP9P9NH57SD serum expression from NSCLC patients and to determine its diagnostic usefulness.

By using stem-loop quantitative real-time PCR, we were able to detect various tRF-31-79MP9P9NH57SD expressions in 96 NSCLC serum samples, 96 healthy controls, and 20 pairs of NSCLC serum samples pre- and post-surgery (qRT-PCR). After that, we analyzed its diagnostic effectiveness using the receiver operating characteristic (ROC) curve.

Serum tRF-31-79MP9P9NH57SD expression was higher in NSCLC patients, and levels of tRF-31-79MP9P9NH57SD were linked to the clinical stage (p = 0.002) and the malignancy of lymph node (p = 0.012). In addition, after the procedure, the serum tRF-31-79MP9P9NH57SD expression in NSCLC patients dropped. With 48.96 percent sensitivity and 90.62 percent specificity, the area under ROC curve (AUC) was 0.733.

serum tRF-31-79MP9P9NH57SD possibly is a new and groundbreaking biomarker for the NSCLC.