Prostate cancer early diagnosis: circulating microRNA pairs potentially beyond single microRNAs upon 1231 serum samples.

The accuracy of prostate-specific antigen or clinical examination in prostate cancer (PCa) screening is in question, and circulating microRNAs (miRNAs) can be alternatives to PCa diagnosis. However, recent circulating miRNA biomarkers either are identified upon small sample sizes or cannot have robust diagnostic performance in every aspect of performance indicators. These may decrease applicability of potential biomarkers for the early detection of PCa. We reviewed recent studies on blood-derived miRNAs for prostate cancer diagnosis and carried out a large case study to understand whether circulating miRNA pairs, rather than single circulating miRNAs, could contribute to a more robust diagnostic model to significantly improve PCa diagnosis. We used 1231 high-throughput miRNA-profiled serum samples from two cohorts to design and verify a model based on class separability miRNA pairs (cs-miRPs). The pairwise model was composed of five circulating miRNAs coupled to miR-5100 and miR-1290 (i.e. five miRNA pairs, 5-cs-miRPs), reaching approximately 99% diagnostic performance in almost all indicators (sensitivity = 98.96%, specificity = 100%, accuracy = 99.17%, PPV = 100%, NPV = 96.15%) shown by a test set (n = 484: PCa = 384, negative prostate biopsies = 100). The nearly 99% diagnostic performance was also verified by an additional validation set (n = 140: PCa = 40, healthy controls = 100). Overall, the 5-cs-miRP model had 1 false positive and 7 false negatives among the 1231 serum samples and was superior to a recent 2-miRNA model (so far the best for PCa diagnosis) with 18 false positives and 80 false negatives. The present large case study demonstrated that circulating miRNA pairs could potentially bring more benefits to PCa early diagnosis for clinical practice.

Peripheral blood molecular measurable residual disease is sufficient to identify patients with acute myeloid leukaemia with imminent clinical relapse.

Longitudinal molecular measurable residual disease (MRD) sampling after completion of therapy serves as a refined tool for identification of imminent relapse of acute myeloid leukaemia (AML) among patients in long-term haematological complete remission. Tracking of increasing quantitative polymerase chain reaction MRD before cytomorphological reappearance of blasts may instigate individual management decisions and has paved the way for development of pre-emptive treatment strategies to substantially delay or perhaps even revert leukaemic regrowth. Traditionally, MRD monitoring is performed using repeated bone marrow aspirations, albeit the current European LeukemiaNet MRD recommendations acknowledge the use of peripheral blood as an alternative source for MRD assessment. Persistent MRD positivity in the bone marrow despite continuous morphological remission is frequent in both core binding factor leukaemias and nucleophosmin 1-mutated AML. In contrast, monthly assessment of MRD in peripheral blood superiorly separates patients with imminent haematological relapse from long-term remitters and may allow pre-emptive therapy of AML relapse.

MiR-22, a serum predictor of poor outcome and therapy response in diffuse large B-cell lymphoma patients.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive, heterogeneous neoplasm where prognostication and therapeutic decision are challenging. The available prognostic tools are not able to identify all patients refractory to treatment. MicroRNAs, small RNAs frequently deregulated in cancer, stably circulate in biofluids, representing interesting candidates for non-invasive biomarkers. Here we validated serum miR-22, an evolutionarily conserved microRNA, as a prognostic/predictive biomarker in DLBCL. Moreover, we found that its expression and release from DLBCL cells are related to therapy response and adversely affect cell proliferation. These results suggest that miR-22 is a promising complementary or even independent non-invasive biomarker for DLBCL management.

The value of lncRNAs as prognostic biomarkers on clinical outcomes in osteosarcoma: a meta-analysis.

BACKGROUND: In recent years, emerging studies have demonstrated critical functions and potential clinical applications of long non-coding RNA (lncRNA) in osteosarcoma. To further validate the prognostic value of multiple lncRNAs, we have conducted this updated meta-analysis. METHODS: Literature retrieval was conducted by searching PubMed, Web of Science and the Cochrane Library (last update by October 2, 2019). A meta-analysis was performed to explore association between lncRNAs expression and overall survival (OS) of osteosarcoma patients. Relationships between lncRNAs expression and other clinicopathological features were also analyzed respectively. RESULTS: Overall, 4351 patients from 62 studies were included in this meta-analysis and 25 lncRNAs were identified. Pooled analyses showed that high expression of 14 lncRNAs connoted worse OS, while two lncRNAs were associated with positive outcome. Further, analysis toward osteosarcoma clinicopathologic features demonstrated that overexpression of TUG1 and XIST indicated poor clinical parameters of patients. CONCLUSIONS: This meta-analysis has elucidated the prognostic potential of 16 lncRNAs in human osteosarcoma. Evidently, desperate expression and functional targets of these lncRNAs offer new approaches for prognosis and therapy of osteosarcoma.

A 3' tRNA-derived fragment produced by tRNALeuAAG and tRNALeuTAG is associated with poor prognosis in B-cell chronic lymphocytic leukemia, independently of classical prognostic factors.

OBJECTIVE: 3' tRNA-derived fragments (3' tRFs) are important epigenetic regulators in normal and pathological conditions. In this study, we aimed to explore the potential value of a 3' tRF as a prognostic and/or screening biomarker for B-cell chronic lymphocytic leukemia (B-CLL). METHODS: Publicly available next-generation sequencing data from 20 B-CLL cases were analyzed, followed by prediction of targets of the most abundantly and ubiquitously expressed 3' tRFs, leading to selection of tRF-LeuAAG/TAG . PBMCs were isolated from blood samples of 91 B-CLL patients and 43 non-leukemic donors, followed by total RNA extraction, in-vitro polyadenylation, and first-strand cDNA synthesis. Next, a real-time quantitative PCR (qPCR) assay was developed for the accurate quantification of tRF-LeuAAG/TAG and applied in all samples, prior to biostatistical analysis. RESULTS: High tRF-LeuAAG/TAG levels are associated with inferior overall survival (OS) of B-CLL patients. The unfavorable significance of tRF-LeuAAG/TAG was independent of established prognostic factors in B-CLL. Stratified Kaplan-Meier OS analysis uncovered the unfavorable prognostic role of high tRF-LeuAAG/TAG levels for patients in Binet A or Rai I stage, negative CD38 expression, mutated, or unmutated IGHV genomic locus. CONCLUSION: Our approach revealed the independent prognostic value of a particular 3' tRF, derived from tRNALeuAAG and tRNALeuTAG (tRF-LeuAAG/TAG ) in B-CLL.

Extra cellular vesicles in blood circulation as biomarkers and messengers of patho-hysiological activity and alterations.

There is an increasing interest in Extracellular Vesicles released by many cells through membrane shedding. In addition to cell signaling, these particles are true messenger cargos, which can carry cell surface proteins, miRNAs and non-coding RNAs to other and distant cells. They are part of the inter-cellular crosstalk and they contribute to transferring biological messages far away from the triggering event. EVs are biomarkers of many diseases, including thrombo-embolic pathology, infections, neurological or metabolic disorders, and malignancy. Their role and significance are presented and discussed in this short review, as consequences of disease and causes of its progression. But they can also be beneficial for tissue healing or repair, and they can be prepared in vitro to be used for cell- targeted treatments. Many identification and measurement methods for EV's are sophisticated, which restricts their use to research studies, but they have, nevertheless, a high laboratory potential for diagnosis, prognosis and evolution as follow-up of many pathologies. New emerging laboratory tools offer more friendly and easy applications for characterizing EVs and testing their associated activity, especially for the procoagulant ones.

Combined serum miR-29c and miR-149 expression analysis as diagnostic genetic markers for colorectal cancer.

Circulating miRNAs gathered much interest in cancer research as noninvasive biomarkers. The aim of this study was to analyze the expression of miR-29c and miR-149 among colorectal cancer (CRC) patients and to explore their diagnostic and prognostic potentials in relation to the clinical and pathological features. The expression levels of miR-29c and miR-149 were evaluated in the sera of 80 CRC patients, 80 colorectal adenoma (CRA) patients, and 80 healthy controls using quantitative real time polymerase chain reaction (PCR). Carcinoembryonic antigen serum levels were assayed using enzyme-linked immunosorbent assay. miR-29c and miR-149 were significantly downregulated among CRC patients compared with CRA and controls (miR-29c, 0.54 ± 0.19 vs. 0.86 ± 0.12, 0.99 ± 0.07, P < 0.001, respectively; miR-149, 0.46 ± 0.19 vs. 0.74 ± 0.012, 1.0 ± 0.22, P < 0.001, respectively). miR-29c and miR-149 significantly associated with advanced stages of CRC, tumor size, and lymphatic metastasis. By using receiver operating characteristic curve analysis, combined miR-29c and miR-149 revealed the highest diagnostic potential for CRA (area under the curve [AUC] = 0.967) from healthy controls as well as the diagnosis of CRC (AUC = 0.98) from CRA. Moreover, combined miRNAs revealed high diagnostic potential for the earlier stages of CRC compared with advanced stages (AUC = 0.96). In conclusion, combined serum miR-29c and miR-149 expression analysis established novel noninvasive biomarker for early CRC diagnosis.

Identification of seven tumor-educated platelets RNAs for cancer diagnosis.

BACKGROUND: Tumor-educated platelets (TEPs) may enable blood-based cancer diagnosis. This study aimed to identify diagnostic TEPs genes involved in carcinogenesis. MATERIALS AND METHODS: The TEPs differentially expressed genes (DEGs) between healthy samples and early/advanced cancer samples were obtained using bioinformatics. Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were used to identify the pathways and functional annotation of TEPs DEGs. Protein-protein interaction of these TEPs DEGs was analyzed based on the STRING database and visualized by Cytoscape software. The correlation analysis and diagnostic analysis were performed to evaluate the diagnostic value of TEPs mRNAs expression for early/advanced cancers. Quantitative real-time PCR (qRT-PCR) was applied to validate the role of DEGs in cancers. RESULTS: TEPs mRNAs were mostly involved in protein binding, extracellular matrix, and cellular protein metabolic process. RSL24D1 was negatively correlated to early-stage cancers compared to healthy controls and may be potentially used for early cancer diagnosis. In addition, HPSE, IFI27, LGALS3BP, CRYM, HBD, COL6A3, LAMB2, and IFITM3 showed an upward trend in the expression from early to advanced cancer stages. Moreover, ARL2, FCGR2A, and KLHDC8B were positively associated with advanced, metastatic cancers compared to healthy controls. Among the 12 selected DEGs, the expression of 7 DEGs, including RSL24D1, IFI27, CRYM, HBD, IFITM3, FCGR2A, and KLHDC8B, were verified by the qRT-PCR method. CONCLUSION: This study suggests that the 7-gene TEPs liquid-biopsy biomarkers may be used for cancer diagnosis and monitoring.

Roles of circulating microRNA(s) in human breast cancer.

miRNAs are short non-coding RNA molecules that regulate the expression of mRNA post-transcriptionally. MiRNAs that are secreted into the circulation, also termed circulating miRNAs, have been studied extensively for their roles in diagnosis, treatment and prognosis of human breast cancer. Breast cancer is the most prevalent female cancer and is associated with key cancer hallmarks including sustained proliferation, evasion of apoptosis, increased invasion, enhanced metastases, initation of inflammation, induction of angiogenesis, metabolic derangement and immune dysregulation. This review aimed to explore the relationships between circulating miRNAs and different breast cancer hallmarks. Besides, the advantages, challenges and clinical application of using circulating miRNAs in human breast cancer management were also discussed.

Nrf2-lncRNA controls cell fate by modulating p53-dependent Nrf2 activation as an miRNA sponge for Plk2 and p21cip1.

Long noncoding RNA (lncRNA) capable of controlling antioxidative capacity remains to be investigated. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a central molecule for cellular defense that increases antioxidative capacity. We identified a novel lncRNA named Nrf2-activating lncRNA (Nrf2-lncRNA) transcribed from an upstream region of the microRNA 122 gene (MIR122). Nrf2-lncRNA existed in the cytoplasm, suggestive of its function as a competing endogenous RNA [ceRNA, microRNA (miRNA) sponge]. Nrf2-lncRNA served as a ceRNA for polo-like kinase (Plk) 2 and cyclin-dependent kinase inhibitor 1 (p21cip1) through binding of miRNA 128 and miRNA 224, inducing Plk2/Nrf2/p21cip1 complexation for Nrf2 activation in the cells under p53-activating conditions (i.e., DNA damage and serum deprivation). Nrf2-lncRNA expression was suppressed with the initiation of apoptosis, being a rheostat for cell fate determination. Nrf2-lncRNA levels correlated with the recurrence-free postsurgery survival rate of patients with hepatocellular carcinoma. Collectively, Nrf2-lncRNA promotes Plk2 and p21cip1 translation by competing for specific miRNAs and activating Nrf2 under surviving conditions from oxidative stress, implying that Nrf2-lncRNA serves as a fine-tuning rheostat for cell fate decision.-Joo, M. S., Shin, S.-B., Kim, E. J., Koo, J. H., Yim, H., Kim, S. G. Nrf2-lncRNA controls cell fate by modulating p53-dependent Nrf2 activation as an miRNA sponge for Plk2 and p21cip1.

Circulating MicroRNAs as Potential Biomarkers for Lung Cancer.

Lung cancer is the number one cause of cancer-related mortality worldwide. To improve disease outcome, it is crucial to implement biomarkers into the clinics which assist physicians in their decisions regarding diagnosis, prognosis, as well as prediction of treatment response. Liquid biopsy offers an opportunity to obtain such biomarkers in a minimal invasive manner by retrieving tumor-derived material from body fluids of the patient. The abundance of circulating microRNAs is known to be altered in disease and has therefore been studied extensively as a cancer biomarker. Circulating microRNAs present a variety of favorable characteristics for application as liquid biopsy-based biomarkers, including their high stability, relatively high abundance, and presence is nearly all body fluids. Although the application of circulating microRNAs for the management of lung cancer has not entered the clinics yet, several studies showed their utility for diagnosis, prognosis, and efficacy prediction of various treatment strategies, including surgery, radio-/chemotherapy, as well as targeted therapy. To compensate for their limited tumor specificity, several microRNAs are frequently combined into microRNA panels. Moreover, the possibility to combine single microRNAs or microRNA panels with tumor imaging or other cancer-specific biomarkers has the potential to increase specificity and sensitivity and could lead to the clinical application of novel multi-marker combinations.

High Expression Levels of Long Noncoding RNA Small Nucleolar RNA Host Gene 18 and Semaphorin 5A Indicate Poor Prognosis in Multiple Myeloma.

BACKGROUND: The aim of this study was to detect the expression of long noncoding RNA small nucleolar RNA host gene 18 (SNHG18) andsemaphorin 5A (SEMA5A) genes in multiple myeloma (MM) patients and to explore the correlation of the expression of these genes with the clinical characteristics and prognosis of MM patients. METHODS: Forty-seven newly diagnosed MM, 18 complete remission MM, 13 refractory/relapse MM, and 22 iron deficiency anemia (serving as control) samples were extracted at the Department of Hematology, Second Affiliated Hospital of Xian Jiaotong University between January 2015 and December 2016. The clinical features of the MM patients are summarized. Real-time quantitative PCR was performed to analyze the relative expression levels of the SNHG18 and SEMA5Agenes. The clinical characteristics and overall survival (OS) of the MM patients were statistically analyzed while measuring different levels of SNHG18 and SEMA5Agene expression. At the same time, the correlation between the expression of SNHG18 and SEMA5A was also analyzed. RESULTS: The analysis confirmed that SNHG18 and its possible target gene SEMA5A were both highly expressed in newly diagnosed MM patients. After analyzing the clinical significance of SNHG18 and SEMA5A in MM patients, we found that the expression of SNHG18 and SEMA5A was related to the Durie-Salmon (DS), International Staging System (ISS), and Revised International Staging System (R-ISS) classification systems, and the Mayo Clinic Risk Stratification for Multiple Myeloma (mSMART; p < 0.05). Moreover, we observed a significant difference in OS between the SNHG18/SEMA5A high expression group and the low expression group. We found a positive correlation between SNHG18 and SEMA5A expression (r = 0.709, p < 0.01). Surprisingly, the expected median OS times of both the SNHG18 and SEMA5Ahigh expression groups were significantly decreased, which was in contrast to those of both the SNHG18 and SEMA5Alow expression groups and the single-gene high expression group (p < 0.05). CONCLUSION: High expression of both SNHG18 and SEMA5A is associated with poor prognosis in patients with MM.

The clinical significance of circulating DSCAM-AS1 in patients with ER-positive breast cancer and construction of its competitive endogenous RNA network.

Long Non-Coding RNAs (lncRNAs), with diagnostic and therapeutic applications in malignancies, are newly described tumour-related molecules. Here, we reported the importance of circulating DSCAM-AS1 as the biomarker to detect Estrogen Receptor (ER)-positive breast cancer (BC) cases. Moreover, the expression of a BC-associated lncRNAs, namely DSCAM-AS1, was measured in tumoural and Paired Adjacent Non-Tumoral (PANT) tissue, as well as plasma, using Real-Time Polymerase Chain Reaction (RT-PCR). Besides, the correlations between gene expression and the clinicopathological features were analyzed. The diagnostic power of circulating DSCAM-AS1 in BC was estimated using the Area Under the Curve (AUC) value. Furthermore, we studied the DSCAM-AS1 associated with the network of competitive endogenous RNA (ceRNA) in BC using the literature review and in silico analysis. We found a significant increase in the expression levels of lncRNA in the tumour (P < 0.001) and in plasma (P < 0.001) of ER-positive BC patients. The sensitivity and specificity of DSCAM-AS1 in plasma for detection of BC from healthy controls were 100 and 97%, respectively (AUC = 0.98, P < 0.001). Accordingly, we suggest an elevated level of circulating DSCAM-AS1 as a candidate biomarker of ER-positive BC patients. Moreover, perturbation of DSCAM-AS1, as a ceRNA, acts in the tumor progression and drug resistance by affecting different cell signaling.

Exosomal piRNA profiling revealed unique circulating piRNA signatures of cholangiocarcinoma and gallbladder carcinoma.

Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are biliary tract cancers with poor five-year survival and high recurrence rates. Both CCA and GBC patients suffer from lack of circulating diagnostic biomarkers at the early stage. Extracellular vesicles, especially exosomes, have been emerged as promising diagnostic sources for cancers due to easy and quick accessibility. Hence, identification of exosomal biomarkers provides a novel strategy for CCA and GBC diagnosis. Here, five CCA patients and four GBC patients were enrolled for exosomal small RNA sequencing. Our data showed that exosomal piwi-interacting RNA (piRNA) populations were altered in the plasma of CCA and GBC patients. In comparison to healthy individuals, 694 and 323 piRNAs were upregulated in CCA and GBC, respectively, while 36 and 191 piRNAs were downregulated. Interestingly, sequencing results predicted that piR-2660989, piR-10506469, piR-20548188, piR-10822895, piR-hsa-23209, and piR-18044111 were upregulated in both CCA and GBC plasma. Importantly, we further included blood samples from 50 health individuals, 40 CCA patients, and 25 GBC patients and found that piR-10506469 were significantly increased in the exosomes of plasma from both CCA and GBC patients. Moreover, we analyzed the expression levels of differentially expressed exosomal piRNAs in the plasma of CCA and GBC patient before and after surgeries and found that piR-10506469 and piR-20548188 were significantly decreased in patients underwent surgeries. Taken together, our data revealed that exosomal piRNAs those are differentially expressed in CCA and GBC plasma may serve as potential biomarkers for the diagnosis of CCA and GBC.

An RNA-based signature enables high specificity detection of circulating tumor cells in hepatocellular carcinoma.

Circulating tumor cells (CTCs) are shed into the bloodstream by invasive cancers, but the difficulty inherent in identifying these rare cells by microscopy has precluded their routine use in monitoring or screening for cancer. We recently described a high-throughput microfluidic CTC-iChip, which efficiently depletes hematopoietic cells from blood specimens and enriches for CTCs with well-preserved RNA. Application of RNA-based digital PCR to detect CTC-derived signatures may thus enable highly accurate tissue lineage-based cancer detection in blood specimens. As proof of principle, we examined hepatocellular carcinoma (HCC), a cancer that is derived from liver cells bearing a unique gene expression profile. After identifying a digital signature of 10 liver-specific transcripts, we used a cross-validated logistic regression model to identify the presence of HCC-derived CTCs in nine of 16 (56%) untreated patients with HCC versus one of 31 (3%) patients with nonmalignant liver disease at risk for developing HCC (P < 0.0001). Positive CTC scores declined in treated patients: Nine of 32 (28%) patients receiving therapy and only one of 15 (7%) patients who had undergone curative-intent ablation, surgery, or liver transplantation were positive. RNA-based digital CTC scoring was not correlated with the standard HCC serum protein marker alpha fetoprotein (P = 0.57). Modeling the sequential use of these two orthogonal markers for liver cancer screening in patients with high-risk cirrhosis generates positive and negative predictive values of 80% and 86%, respectively. Thus, digital RNA quantitation constitutes a sensitive and specific CTC readout, enabling high-throughput clinical applications, such as noninvasive screening for HCC in populations where viral hepatitis and cirrhosis are prevalent.

Current and New Predictors for Treatment Response in Metastatic Colorectal Cancer. The Role of Circulating miRNAs as Biomarkers.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer in the world. More than half of all CRC patients will eventually develop metastases and require treatment accordingly, but few validated predictive factors for response to systemic treatments exist. In order to ascertain which patients benefit from specific treatments, there is a strong need for new and reliable biomarkers. We conducted a comprehensive search using the PUBMED database, up to December 2019, in order to identify relevant studies on predictive biomarkers for treatment response in metastatic CRC. We will herein present the currently used and potential biomarkers for treatment response and bring up-to-date knowledge on the role of circulating microRNAs, associated with chemotherapy and targeted therapy regimens used in metastatic CRC treatment. Molecular, tumor-related, disease-related, clinical, and laboratory predictive markers for treatment response were identified, mostly proposed, with few validated. Several circulating microRNAs have already proven their role of prediction for treatment response in CRC, but future clinical studies are needed to confirm their role as biomarkers across large cohorts of patients.

Deep Sequencing of Small RNAs from Neurosurgical Extracellular Vesicles Substantiates miR-486-3p as a Circulating Biomarker that Distinguishes Glioblastoma from Lower-Grade Astrocytoma Patients.

Extracellular vesicles (EVs) play key roles in glioblastoma (GBM; astrocytoma grade IV) biology and are novel sources of biomarkers. EVs released from GBM tumors can cross the blood-brain-barrier into the periphery carrying GBM molecules, including small non-coding RNA (sncRNA). Biomarkers cargoed in circulating EVs have shown great promise for assessing the molecular state of brain tumors in situ. Neurosurgical aspirate fluids captured during tumor resections are a rich source of GBM-EVs isolated directly from tumor microenvironments. Using density gradient ultracentrifugation, EVs were purified from cavitron ultrasonic surgical aspirate (CUSA) washings from GBM (n = 12) and astrocytoma II-III (GII-III, n = 5) surgeries. The sncRNA contents of surgically captured EVs were profiled using the Illumina® NextSeqTM 500 NGS System. Differential expression analysis identified 27 miRNA and 10 piRNA species in GBM relative to GII-III CUSA-EVs. Resolved CUSA-EV sncRNAs could discriminate serum-EV sncRNA profiles from GBM and GII-III patients and healthy controls and 14 miRNAs (including miR-486-3p and miR-106b-3p) and cancer-associated piRNAs (piR_016658, _016659, _020829 and _204090) were also significantly expressed in serum-EVs. Circulating EV markers that correlate with histological, neuroradiographic and clinical parameters will provide objective measures of tumor activity and improve the accuracy of GBM tumor surveillance.

Differential expression of matrix metalloproteinases and miRNAs in the metastasis of oral squamous cell carcinoma.

BACKGROUND: Our study aimed to reveal the regulatory mechanisms of miRNAs and matrix metalloproteinases (MMPs) in oral squamous cell carcinoma (OSCC). METHODS: The mRNA and miRNA expression profiles of six metastatic tumour samples, six nonmetastatic tumour samples, and six normal tissue samples were used for microarray analysis. Moreover, the important genes and miRNAs were validated by published profiles in Oncomine and by qRT-PCR. RESULTS: MMP7, MMP13, and MMP10 were upregulated, and MMP12 and MMP9 were downregulated in metastatic tumours compared with nonmetastatic tumours. MMP7 was regulated by miR-4697-5p and miR-7109-5p. MMP7 and MMP13 were upregulated in OSCC samples compared with normal samples in Oncomine. Moreover, qRT-PCR revealed that the expression of miR-7109-5p and miR-34b was decreased in metastatic tumours compared with nonmetastatic tumours. CONCLUSIONS: Our study suggested that miR-7109-5p and miR-34b might play important roles in the metastasis of OSCC by regulating MMP7 and MMP13 expression, respectively.

Cancer-Related Ischemic Stroke Has a Distinct Blood mRNA Expression Profile.

Background and Purpose- Comorbid cancer is common in patients with acute ischemic stroke (AIS). As blood mRNA profiles can distinguish AIS mechanisms, we hypothesized that cancer-related AIS would have a distinctive gene expression profile. Methods- We evaluated 4 groups of 10 subjects prospectively enrolled at 3 centers from 2009 to 2018. This included the group of interest with active solid tumor cancer and AIS and 3 control groups with active cancer only, AIS only, or vascular risk factors only. Subjects in the AIS-only and cancer-only groups were matched to subjects in the cancer-stroke group by age, sex, and cancer type (if applicable). Subjects in the vascular risk factor group were matched to subjects in the cancer-stroke and stroke-only groups by age, sex, and vascular risk factors. Blood was drawn 72 to 120 hours after stroke. Total RNA was processed using 3' mRNA sequencing. ANOVA and Fisher least significant difference contrast methods were used to estimate differential gene expression between groups. Results- In the cancer-stroke group, 50% of strokes were cryptogenic. All groups had differentially expressed genes that could distinguish among them. Comparing the cancer-stroke group to the stroke-only group and after accounting for cancer-only genes, 438 genes were differentially expressed, including upregulation of multiple genes/pathways implicated in autophagy signaling, immunity/inflammation, and gene regulation, including IL (interleukin)-1, interferon, relaxin, mammalian target of rapamycin signaling, SQSTMI1 (sequestosome-1), and CREB1 (cAMP response element binding protein-1). Conclusions- This study provides evidence for a distinctive molecular signature in blood mRNA expression profiles of patients with cancer-related AIS. Future studies should evaluate whether blood mRNA can predict detection of occult cancer in patients with AIS. Clinical Trial Registration- URL: https://clinicaltrials.gov. Unique identifier: NCT02604667.

Circulating microRNAs as potential diagnostic biomarkers and therapeutic targets in prostate cancer: Current status and future perspectives.

Prostate cancer (PCa) is one of the most common malignancies among men. Despite advancement in technology and medicine over past decades, late diagnosis remains a critical milestone in effective treatment. Therefore, it is necessary to identify novel and reliable biomarkers which are specifically sensitive and specific for prognosis and prediction of clinical outcomes. MicroRNAs (miRNAs) play important roles in posttranslational regulations of genes. Circulating and exosomal miRNAs can be applied as useful diagnostic markers for a different type of malignancies, including PCa. Herein, we summarized various roles of miRNAs (diagnostic, therapeutic, and prognostic) in PCa. Moreover, we highlighted exosomal miRNAs as a new candidate in diagnosis and monitoring response to therapy in patients with PCa.