Early pregnancy loss is the most common complication of human reproduction. Given the complexities of early development, it is likely that many mechanisms are involved. Knowledge of differences in protein expression in parallel profiling is essential to understand the comprehensive pathophysiological mechanism underlying early pregnancy loss. To identify proteins with different expression profiles related to early pregnancy loss, we applied a proteomic approach and performed two-dimensional gel electrophoresis (2-DE) on six placental villous tissues from patients with early pregnancy loss and six from normal pregnant women, followed by comparison of the silver-stained 2-DE profiles. It was found that 13 proteins were downregulated and 5 proteins were upregulated significantly (P < 0.05) in early pregnancy loss as determined by spot volume. Among them, 10 downregulated and 2 upregulated spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Anomalies of these proteins, including three principal antioxidant enzymes (copper/zinc-superoxide dismutase, peroxiredoxin 3, and thioredoxin-like 1 protein), S100 calcium binding protein, galectin-1, chorionic somatomammotropin hormone 1, transthyretin, fas inhibitory molecule, eukaryotic translation elongation factor, RNA-binding protein, ubiquitin-conjugating enzyme E2N, and proteasome beta-subunit, indicate widespread failure in cell regulations and processes such as antioxidative defense, differentiation, cell proliferation, metabolism, apoptosis, transcription, and proteolysis in early pregnancy loss. This study has identified several proteins that are associated with placentation and early development, shedding a new insight into the proteins that may be potentially involved in the pathophysiological mechanisms underlying early pregnancy loss.
Background/Aims: Exosomal circulating long non-coding RNAs (lncRNAs) in blood are emerging as clinically useful and non-invasive biomarkers for tumor diagnosis. However, normal cells can also secrete exosomes, so it is a prerequisite to obtain tumor-derived exosomes for better understanding of their diagnostic impacts in cancer. In this study, a dual-antibody-functionalized immunoaffinity system was established to isolate exosomes and investigate their lncRNAs expression pattern and clinical significance in prostate cancer (PCa). Methods: A commercially available kit was used to isolate total exosomes, which were then purified by a dual-antibody-functionalized immunoaffinity system. RT-qPCR was performed to detect the expression of exosomal lncRNAs. Receiver operating characteristic (ROC) curves were plotted to assess the diagnostic value. Results: Expression levels of two lncRNAs in tumor-derived exosomes were significantly higher than those in total exosomes. The levels of SAP30L-AS1 were upregulated in benign prostatic hyperplasia (BPH), and SChLAP1 levels were significantly higher in PCa than in BPH and healthy individuals. The area under the ROC curve indicated that SAP30L-AS1 and SChLAP1 had adequate diagnostic value to distinguish PCa from controls. Two lncRNAs separately combined with prostate specific antigen (PSA) possessed a moderate ability for discrimination. SAP30L-AS1 expression level was related to PSA values and tumor invasion. SChLAP1 expression was significantly higher in patients with higher Gleason scores, and was also effective in differentiating between BPH and PCa when the concentration of PSA was in the gray zone. Conclusion: The isolation of tumor-derived exosomes by dual-antibody-functionalized immunoaffinity systems and detection of their lncRNAs in plasma may lead to the identification of suitable biomarkers, with potential diagnostic utility.
BackgroundTissue biopsy-based cancer diagnosis has limitations because of the fact that tumor tissues are in constant evolution and extremely heterogeneous. The current study was aimed to examine whether tumor-educated blood platelets (TEPs) might be a potential all-in-one source for blood-based cancer diagnostics to overcome the limitations of conventional cancer biopsy.MethodsIn the present study, we evaluated the expression pattern of MAGI2 antisense RNA 3 (MAGI2-AS3) and ZNFX1 antisense RNA 1 (ZFAS1) in both plasma and platelets of 101 non-small-cell lung cancer (NSCLC) patients. Receiver operating characteristic (ROC) curve was generated to evaluate their diagnostic potential. In addition, epidermal growth factor receptor (EGFR) mutations were detected in DNA and RNA samples of platelets for companion diagnostics.ResultsOur results showed that the levels of MAGI2-AS3 and ZFAS1 in both plasma and platelets of NSCLC patients were significantly downregulated than those in healthy controls. A positive correlation of long noncoding RNA expression was observed between platelets and plasma (r=0.738 for MAGI2-AS3, r=0.751 for ZFAS1, respectively). By ROC analysis, we found that molecular interrogation of MAGI2-AS3 and ZFAS1 in TEPs and plasma can offer valuable diagnostic performance for NSCLC patients (area under the ROC curve [AUC]MAGI2-AS3= 0.853/0.892, and AUCZFAS1=0.780/0.744 for diagnosing adenocarcinoma and squamous cell carcinoma cases from controls, respectively). Clinicopathologic characteristic analysis further revealed that MAGI2-AS3 level significantly correlated with tumor–node–metastasis (TNM) stage (p=0.001 in TEPs, p=0.003 in plasma), lymph-node metastasis (p=0.016 in TEPs, p=0.023 in plasma), and distant metastasis (p=0.045 in TEPs, p=0.045 in plasma), while ZFAS1 level was only correlated with TNM stage (p=0.005 in TEPs, p=0.044 in plasma). Furthermore, EGFRvIII RNA existed in both TEPs and plasma, but EGFR intracellular mutations cannot be detected in DNA of TEPs isolated from NSCLC.ConclusionOur data suggested that TEP is a promising source for NSCLC diagnosis and companion diagnostics.
Objective: To investigate the potential biomarkers for venous metastasis of hepatocellular carcinoma (HCC), and briefly discuss their target genes and the signaling pathways they are involved in.Materials and Method: The dataset GSE6857 was downloaded from GEO. Significantly differentially expressed miRNAs were identified using the R package “limma,” After that, the survival analysis was conducted to discover the significance of these up-regulated miRNAs for the prognosis of HCC patients. Additionally, miRNAs which were up-regulated in venous metastasis positive HCC tissues and were significant for the prognosis of HCC patients were further verified in clinical samples using RT-qPCR. The miRNAs were then analyzed for their correlations with clinical characteristics including survival time, AFP level, pathological grade, TNM stage, tumor stage, lymph-node metastasis, distant metastasis, child-pugh score, vascular invasion, liver fibrosis and race using 375 HCC samples downloaded from the TCGA database. The target genes of these miRNAs were obtained using a miRNA target gene prediction database, and their functions were analyzed using the online tool DAVID.Results: 15 miRNAs were differentially expressed in samples with venous metastasis, among which 7 were up-regulated in venous metastasis positive HCC samples. As one of the up-regulated miRNAs, hsa-miR-210 was identified as an independent prognostic factor for HCC. Using RT-qPCR, it was evident that hsa-miR-210 expression was significantly higher in venous metastasis positive HCC samples (p = 0.0036). Further analysis indicated that hsa-miR-210 was positively associated with AFP level, pathological grade, TNM stage, tumor stage and vascular invasion. A total of 168 hsa-miR-210 target genes, which are mainly related to tumor metastasis and tumor signaling pathways, were also predicted in this study.Conclusion: hsa-miR-210 might promote vascular invasion of HCC cells and could be used as a prognostic biomarker.
Background: miRNAs dysregulate in hepatocellular carcinoma (HCC), showing promise for diagnostic biomarkers which may be found through exploration of differentially expressed miRNAs when comparing HCC and normal liver tissues.Materials and Methods: In the present research, candidate miRNAs were selected and verified using screening dataset GSE12717 and training dataset GSE10694, respectively. A miRNA combination was constructed using stepwise logistic regression analysis and validated using two datasets GSE74618 and TCGA. Target genes of miRNAs in the combination were obtained using a miRNA target gene prediction database. Functional analysis was conducted using an online tool DAVID. We also analyzed the mRNA-Seq data of project LIHC from TCGA to identify the hub target genes of the miRNAs.Results: A miRNA combination, which is composed of hsa-miR-221 and hsa-miR-29c was defined in this study. The miRNA combination is more effective in discriminating HCC patients from normal individuals than individual miRNAs. Additionally, the combined miRNAs showed a lower misdiagnosis rate than AFP in HCC diagnosis. In terms of the functional analysis, a total of 27 target genes of hsa-miR-221 and 96 target genes of hsa-miR-29c were obtained. Among which, INSIG1 was the common target of the two miRNAs. It was also found that both previously mentioned miRNAs played important roles in the regulation of transcription, cell proliferation, and involvement in cancer-related pathways. Lastly, 2 hub target genes of hsa-miR-221 and 16 hub target genes of hsa-miR-29c were obtained.Conclusion: We established a miRNA combination as a promising tool for HCC diagnosis, and the target genes we predicted provide possible points of penetration for researching these two miRNAs in HCC.
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