A comparative study of two liquid-based preparation methods: membrane-based and sedimentation in fine needle aspiration cytology diagnosis in thyroid nodules.

BACKGROUND: As thyroid fine needle aspiration (FNA) shows a certain limitation in the diagnosis of conventional smears, novel approaches like liquid-based cytology (LBC) have been gradually applied recently. Studies have shown the difference between the conventional smears (CSs) and liquid-based smears on fine needle aspiration cytology (FNAC) diagnosis, but the impacts of different liquid-based preparation (LBP) methods, including membrane-based and sedimentation, on diagnosis are still not clear. In this study, the effects of liquid-based smears prepared by different methods on the cytological interpretation were studied. METHODS: A total of 221 thyroid liquid-based FNAC cases from January 2017 to October 2018 were collected. We retrospectively studied and compared the effects of the membrane-based and sedimentation LBP methods through The Bethesda System for Reporting Thyroid Cytopathology (TBS) diagnosis and risk of malignancy assessment. Besides, we made an evaluation on the diagnostic differences in the effects of different preparation methods on the cell morphology and tissue structure of papillary thyroid carcinoma (PTC) for more accurate FNAC diagnosis. RESULTS: Among the 221 cases reviewed, membrane-based method was applied in 153 cases and sedimentation in 68 cases. According to the diagnostic criteria of 2017 TBS, TBSVI and TBSV thyroid could be cytologically diagnosed by membrane-based (49.0% (75/153) and 25.5% (39/153)) and sedimentation (52.9(36/68) and 25(17/68)) methods, and both were confirmed as PTC through histopathological diagnosis after operation, with the malignancy degree as high as 100%. In addition, of the 30 cases that were diagnosed as TBSIII thyroid nodules with the membrane-based method, 15 cases were pathologically malignant after an operation, with the malignancy degree of 50% (15/30), while that in 11 cases using the sedimentation method was 45.4% (5/11). PTC could be detected in both the TBSIV and TBSII thyroid nodules diagnosed by membrane-based method, with the sensitivity of 87.0% (114/131) lower than that by sedimentation method (91.4% (53/58)), showing the lower consistency with the histopathological result (K = 0.635 vs K = 0.757). Among the membrane-based smears, 23.5% (36/153) had fewer follicular epithelial cells, 55.6% (20/36) of which were considered to be suspicious for PTC from cell karyotype and tissue arrangement. While among the sedimentation smears, 16.2% (11/68) had fewer follicular epithelial cells, and 63.6% (7/11) was suspicious for PTC. In 72.5% (95/131) membrane-based smears of PTC, the papillary and swirling structures were not obvious, showing as crowded syncytial cell masses, while in 55.2% (32/58) sedimentation smears, both structures were visible with obvious three-dimensional papillary structure, and the fibrovascular axis still remained. CONCLUSION: LBP technique is feasible for FNAC diagnosis, and the sedimentation shows more advantages, like higher PTC detection rate and good consistency with postoperative histopathological diagnosis. A clear understanding of the subtle differences in the effects of membrane-based and sedimentation methods on the cell morphology and tissue structure could be conducive to the definitive diagnosis of PTC before operation.

The potential of microRNAs as human prostate cancer biomarkers: A meta-analysis of related studies.

Prostate cancer (PC) is a very important kind of male malignancies. When PC evolves into a stage of hormone resistance or metastasis, the fatality rate is very high. Currently, discoveries and advances in miRNAs as biomarkers have opened the potential for the diagnosis of PC, especially early diagnosis. miRNAs not only can noninvasively or minimally invasively identify PC, but also can provide the data for optimization and personalization of therapy. Moreover, miRNAs have been shown to play an important role to predict prognosis of PC. The purpose of this meta-analysis is to integrate the currently published expression profile data of miRNAs in PC, and evaluate the value of miRNAs as biomarkers for PC. All of relevant records were selected via electronic databases: Pubmed, Embase, Cochrane, and CNKI based on the assessment of title, abstract, and full text. we extracted mean ± SD or fold change of miRNAs expression levels in PC versus BPH or normal controls. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and recurrence-free survival (RFS), were also calculated to detect the relationship between high miRNAs expression and PC prognosis. Selected 104 articles were published in 2007-2017. According to the inclusion criteria, 104 records were included for this meta-analysis. The pooled or stratified analyze showed 10 up-regulated miRNAs (miR-18a, miR-34a, miR-106b, miR-141, miR-182, miR-183, miR-200a/b, miR-301a, and miR-375) and 14 down-regulated miRNAs (miR-1, miR-23b/27b, miR-30c, miR-99b, miR-139-5p, miR-152, miR-187, miR-204, miR-205, miR-224, miR-452, miR-505, and let-7c) had relatively good diagnostic and predictive potential to discriminate PC from BPH/normal controls. Furthermore, high expression of miR-32 and low expression of let-7c could be used to differentiate metastatic PC from local/primary PC. Additional interesting findings were that the expression profiles of five miRNAs (miR-21, miR-30c, miR-129, miR-145, and let-7c) could predict poor RFS of PC, while the evaluation of miR-375 was associated with worse OS. miRNAs are important regulators in PC progression. Our results indicate that miRNAs are suitable for predicting the different stages of PC. The detection of miRNAs is an effective way to control patient's prognosis and evaluate therapeutic efficacy. However, large-scale detections based on common clinical guidelines are still necessary to further validate our conclusions, due to the bias induced by molecular heterogeneity and differences in study design and detection methods.

Predictive significance of TMRPSS2-ERG fusion in prostate cancer: a meta-analysis.

BACKGROUND: Prostate cancer is a major malignancy in males. TMPRSS2-ERG is a high-frequency fusion gene expressed in prostate cancer and plays a vital role in carcinogenesis. Recent studies showed that TMPRSS2-ERG is a potential predictive biomarker for prostate cancer. However, the predictive value of TMPRSS2-ERG fusion is yet unclear. METHODS: A total of 76 relevant articles, published from 2015 to 2017, were obtained from PubMed, Web of Science, EMBASE, Scopus, the Cochrane Library, and CNKI databases to investigate the predictive significance of TMPRSS2-ERG fusion in prostate cancer. Pooled odds ratio (ORs) with 95% confidence intervals (CIs) were calculated to estimate the correlation between TMPRSS2-ERG fusion gene and tumor features. RESULTS: The pooled or stratified analysis showed that the TMPRSS2-ERG fusion gene had a highly predictive potential. First, TMPRSS2-ERG fusion was associated with T-stage at diagnosis (T3-4 vs. T1-2 OR: 1.40; 95% CI 1.33-1.48) and metastasis (M1 vs. M0 OR: 1.35; 95% CI 1.02-1.78) but not with biochemical recurrence or prostate cancer-specific mortality. Furthermore, the subgroup analysis found that the TMPRSS2-ERG fusion gene was correlated with Gleason (G) scores, and the fusion was common in prostate cancer with G ≤ 7. Additionally, the meta-analysis demonstrated that the fusion was likely to occur in young patients (> 65 vs. ≤ 65 OR: 0.68; 95% CI 0.52-0.89), in patients with high PSA levels (> 10 vs. ≤ 10 OR: 1.30; 95% CI 1.21-1.38), and in patients with peripheral involvement (positive vs. negative OR: 1.17; 95% CI 1.08-1.28), while not associated with tumor volume. Finally, the subgroup analysis of different fusion types demonstrated that the deletion-type fusion was significantly associated with the malignant degree of prostate cancer (pooled OR: 5.67; 95% CI 2.85-11.28). Moreover, the deletion-type was common in Africa patients, followed by Caucasian patients, and no significant difference was observed in the incidence of different fusion types in the Asian population. CONCLUSIONS: The meta-analysis findings suggested that the TMPRSS2-ERG fusion gene might be a predictive marker for prostate cancer patients, and might be valuable for assessing the characteristics of prostate cancer for individualized treatment and prognosis evaluation.

Expression profile analysis of microRNAs in prostate cancer by next-generation sequencing.

BACKGROUND: Prostate cancer (PCa) is the second leading cause of tumor mortality among males in western societies. In China, the diagnostic and fatality rate of PCa is increasing yearly. METHODS: To characterize underlying molecular mechanisms, the microRNA (miRNA) profile of high-grade PCa, low-grade PCa, and benign prostate hyperplasia (BPH) were compared using high-throughput Illumina sequencing and quantitative real-time PCR (qRT-PCR) methods. Moreover, a variety of biological information softwares and databases were applied to predict the target genes of miRNA, molecular functions, and signal pathways. RESULTS: Eighteen miRNAs were differentially expressed (fold change ≥ 2, P < 0.05), of which thirteen were upregulated and five were downregulated by sequencing. This was confirmed by qRT-PCR in more clinical tissue samples. In the tumors, miRNAs (miR-125b-5p, miR-126-5p, miR-151a-5p, miR-221-3p, and miR-222-3p) were significantly upregulated with downregulation of miR-486-5p. In addition, 13 novel miRNAs were identified from three prostate tissue libraries, with 12 of them assayed in 21 human normal tissues by qRT-PCR. Multiple databases indicated target genes for these differentially expressed miRNAs. Function annotation of target genes indicated that most of them tend to target genes involved in signal transduction and cell communication, especially cancer-related PI3K-Akt and p53 signaling pathway. CONCLUSIONS: The small RNA transcriptomes obtained in this study uncovers six differentially expressed miRNAs and 12 novel miRNAs, and provides a better understanding of the expression and function of miRNAs in the development of PCa and reveals several miRNAs in PCa that may have biomarker and therapeutic potentials.

Expression prolife and role of miRNAs in prostate cancer.

miRNAs are a class of noncoding RNA molecules about 18-25 nt in length. As key gene expression regulatory factors, they may inhibit or degrade mRNA by incompletely or completely complement to mRNA. Their abnormal expressions are closely related with the carcinogenesis of prostate cancer (PCa). Some miRNAs trigger cancer, while others inhibit the malignant changes. In this article we summarize the latest information on miRNAs expression prolifing and potential biomarkers,in particular the roles of miRNAs in PCa.

Implications of the changes in serum neutrophil gelatinase-associated lipocalin and cystatin C in patients with chronic kidney disease.

AIM: Early intervention in patients with chronic kidney disease (CKD) significantly improves the prognosis. The present widely used markers of renal function, such as serum creatinine (sCr), fail to reflect early renal damage and predict the progression of disease. The authors aimed to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL), a novel specific biomarker of acute kidney injury, could predict the progression of CKD. METHODS: We identified 92 patients with stage 2-4 CKD caused by primary chronic glomerulonephritis. The patients were followed for 2 years, the changes in NGAL levels in the progressive and non-progressive groups were compared. RESULTS: First, the serum NGAL levels of patients with stage 2-4 CKD were significantly increased compared with the control group. Second, based on Pearson correlation analysis, positive correlations existed between NGAL and cystatin C levels and between NGAL and sCr levels. Third, bounded by the progress of renal function, the area under the curve of serum NGAL was 0.872 (95% confidence interval, 0.786-0.933), which suggests a blood NGAL cut-off level of 246 ng/mL (sensitivity 85.19%, specificity 81.54%). Fourth, Kaplan-Meier survival curve analysis showed that the serum NGAL level was closely related to the end-point of renal function in patients with CKD. Fifth, Cox multivariate regression analysis showed that the estimated glomerular filtration rate and blood NGAL are associated with progression of CKD. CONCLUSION: Serum NGAL is an effective biomarker for detecting early-stage renal damage in CKD patients. Serum NGAL was significantly correlated with the severity of renal damage and the progression of renal function deterioration.

Lin28 Mediates Cancer Chemotherapy Resistance via Regulation of miRNA Signaling.

Chemotherapy resistance is one of the major obstacles limiting the success of cancer drug treatment. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to P-Glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. Lin28 is a highly conserved RNA-binding protein, it consists of a cold shock domain and retroviral-type (CCHC) zinc finger motifs. In previous preclinical and clinical studies, positive Lin28 expression in cancer cells was correlated with decreased sensitivity to chemotherapy. And Lin28 could mediate cancer chemotherapy resistance via regulation of miR107 and Let-7 MiRNA. This article reviews current knowledge on predictive value of Lin28 in response to chemotherapy. Better understanding of its role may facilitate patient's selection of therapeutic regimen and lead to optimal clinical outcome.

lncRNA MIAT promotes luminal B breast cancer cell proliferation, migration, and invasion in vitro.

Long noncoding RNAs (lncRNAs) play a role in the emergence and progression of several human tumors, including luminal B breast cancer (BC). The biological functions and potential mechanisms of lncRNA myocardial infarction-associated transcripts (MIAT) in luminal B BC, on the contrary, are unknown. In this work, we used UALCAN database analysis to find high expression of lncRNA MIAT in luminal BC tissues and also confirmed high levels of lncRNA MIAT expression in luminal B BC tissues and cells. In vitro knockdown of MIAT inhibited the proliferation, migration, and invasion of BT474 cells. In addition, we found that miR-150-5p levels were significantly reduced in luminal B BC specimens and cells, and miR-150-5p levels were significantly increased when MIAT was knocked down. And TIMER database analysis showed that MIAT was positively associated with PDL1. Through bioinformatic tools and in vitro experiments, lncRNA MIAT could function as a competitive endogenous RNA (CeRNA) to further regulate programmed cell death ligand 1 (PDL1) expression by directly sponging miR-150-5p. In conclusion, our data suggest that MIAT, an oncogene, may sponge miR-150-5p to regulate PDL1 expression and affect proliferation, migration, and invasion in luminal B BC in vitro.

The first case of Odoribacter splanchnicus bacteremia isolated from a patient in China.

Background: Odoribacter splanchnicus is an extremely rare pathogen of human infection. This case reports bacteremia infection of O. splanchnicus, which is highly likely to result in misdiagnosis if inappropriate diagnostic method are used. Case presentation: A 29-year-old Chinese male patient with no underlying disease was hospitalized twice for injuries caused by a car accident. During the second hospitalization, abdominal surgery was performed and high fever developed after the surgery. A strain of O. splanchnicus was isolated from the blood and confirmed by MALDI-TOF-MS and 16S rRNA gene analysis. Finally, the patient recovered successfully by using antibiotics, fluid replacement and albumin input. Conclusions: This is the first case of O. splanchnicus bacteremia in China. We present a brief review of the cases concerning O. splanchnicus infection in humans. O. splanchnicus, as part of the normal intestinal flora, is well known for its anti-tumor and immune regulating properties, it is rarely isolated from clinical samples. This case illustrates the potential of O. splanchnicus as a pathogen and suggests attention to the use of new and advanced methods like MALDI-TOF MS and 16S rRNA gene sequencing to identify rarely isolated species from clinical samples.

Causality between depression and ankylosing spondylitis in a European population: Results from a Mendelian randomization analysis.

The aim of this study was to explore the application of Mendelian randomization (MR) Egger and inverse variance weighted (IVW) in a causal effect on depression and ankylosing spondylitis (AS). Instrumental variables (IVs) were determined using genome-wide association studies. The 2-sample MR analysis was conducted by MR Egger to test the causal effect between depression and AS. The pleiotropy of potential instrumental variables was evaluated. The results of MR Egger and IVW were further compared. A total of 3 single nucleotide polymorphisms as the construct IVs were included. IVW results showed a significant causal effect between depression and AS (P < .001). Depression could promote the risk of AS (odds ratio = 1.060, 95% confidence interval: 1.026-1.094). However, the MR Egger showed no causal effect (P = .311). Heterogeneity statistics suggested that no heterogeneity was existed (P > .05). It was also suggested that there was no horizontal pleiotropy in IVs (MR Egger intercept: -0.0004, P = .471). Reverse MR analysis suggested that there was no causal effect between AS and depression (P > .05). Gene expression quantitative trait locus (QTLs) suggested that rs2517601 and RNF39 were positively correlated (beta = 1.066, P < .001). Depression may be one of the causes of AS by MR analysis in a European population. We can estimate the causal effect based on IVW when horizontal pleiotropy is very tiny.

Recent research and clinical progress of CTLA-4-based immunotherapy for breast cancer.

Breast cancer is characterized by a high incidence rate and its treatment challenges, particularly in certain subtypes. Consequently, there is an urgent need for the development of novel therapeutic approaches. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) is currently gaining momentum for the treatment of breast cancer. Substantial progress has been made in clinical studies employing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors for breast cancer, but the cure rates are relatively low. To improve the efficacy of CTLA-4-based therapy for breast cancer, further research is imperative to explore more effective immune-based treatment strategies. In addition to monotherapy, CTLA-4 inhibitors are also being investigated in combination with other ICIs or alternative medications. However, it should be noted that immune-based treatments may cause adverse events. This review focuses on the mechanisms of CTLA-4 inhibitor monotherapy or combination therapy in breast cancer. We systematically summarize the latest research and clinical advances in CTLA-4-based immunotherapy for breast cancer, providing new perspectives on the treatment of breast cancer. In addition, this review highlights the immune-related adverse events (irAEs) associated with CTLA-4 inhibitors, providing insights into the development of appropriate clinical tumor immunotherapy regimens and intervention strategies.

Overview of research on fusion genes in prostate cancer.

Fusion genes are known to drive and promote carcinogenesis and cancer progression. In recent years, the rapid development of biotechnologies has led to the discovery of a large number of fusion genes in prostate cancer specimens. To further investigate them, we summarized the fusion genes. We searched related articles in PubMed, CNKI (Chinese National Knowledge Infrastructure) and other databases, and the data of 92 literatures were summarized after preliminary screening. In this review, we summarized approximated 400 fusion genes since the first specific fusion TMPRSS2-ERG was discovered in prostate cancer in 2005. Some of these are prostate cancer specific, some are high-frequency in the prostate cancer of a certain ethnic group. This is a summary of scientific research in related fields and suggests that some fusion genes may become biomarkers or the targets for individualized therapies.

Tax1 enhances cancer cell proliferation via Ras-Raf-MEK-ERK signaling pathway.

Erbin is an ErbB2 binding protein, which belongs to the LAP (leucine-rich repeat (LRR) and PDZ domain) protein family. We previously reported that Tax1, a protein of the human T-cell leukemia virus type I (HTLV-I), associated with Erbin by using Erbin PDZ domain as a bait to screen a human T lymphocyte cDNA library by a yeast two hybrid strategy. In the present study, we demonstrated that Tax1 enhances cancer cell proliferation via Ras-Raf-MEK-ERK signaling pathway by using molecular section strategy. The pull-down assay showed that the four amino acid domain, that is, Tax1 350-353, might specifically interact with Erbin, but not any other Tax1 deletion mutants. The coimmunoprecipitation assay confirmed that Tax1 350-353 domain bound with Erbin in vivo. Functional study demonstrated that overexpression of Tax1 in cancer cell lines of liver cancer SMMC-7721, colon cancer HCT-116, and breast cancer MCF-7 facilitated the cell proliferation. And the transfection of Tax1 353 in MCF-7 cells with endogenous Erbin expression markedly increased phosphorylation of Ras, Raf, MEK1/2, ERK1/2, PI3K, and IkappaBalpha, suggesting that Tax1-enhanced cell proliferation tracks Ras-Raf-MEK-ERK signaling pathway.

Research status and progress of the RNA or protein biomarkers for prostate cancer.

Prostate cancer is a kind of male malignancy. Recently, a large number of studies have reported many potential biomarkers for the diagnosis and prognosis of prostate cancer. In this literature review, we have collected a number of potential biomarkers for prostate cancer reported in the last 5 years. Among them, some are undergoing Phase III clinical trials, and others have been approved by the US Food and Drug Administration. However, most are still in the period of basic research. The review will contribute to future research to find the biomarkers to guide clinicians to make personalized treatment decisions for each prostate cancer patient.

[Identification of binding proteins to the PDZ domain of ERBIN].

OBJECTIVE: To identify the binding proteins to PDZ domain of ERBIN. METHODS: Using PDZ domain of ERBIN as the bait, yeast two-hybrid technology was employed to screen the human lymphocyte leukemia cells MATCHMAKER cDNA library. The protein interaction was identified by immunoprecipitation. RESULTS: A PDZ-binding protein, TAX1, was identified. CONCLUSION: TAX1 is a novel binding protein to PDZ domain of ERBIN.

[The effects of mutant site G81R of RAB5A on RAB5A function].

To study the effects of mutant site G81R of RAB5A, two antisense RNA of RAB5A G81R and RAB5A were inserted into pcDNA3. 1/V5-His TOPO expression vector, and transfected into Anip973, respectively, then detected the protein expressional level of RAB5A by Western blot. Finally, we synchronized Anip973 and the two transfected cells at G0/G1, released cells at G0/G1 by culture medium containing FBS, and sequentially analyzed the percentage of cells at G0/G1, S and G2/M by FCM. The expression of RAB5A may be completely blocked by the antisense RNA of RAB5A G81R, while the antisense RNA of RAB5A partially blocked expression of RAB5A. Furthermore, cell cycle of Anip973 was reciprocity to the protein expressional level of RAB5A. The antisense RNA of RAB5A G81R effectively blocked the expression of RAB5A in Anip973. Cell cycle was lengthened by blocking or reducing expression of RAB5A G81R.