Peripheral blood non-canonical small non-coding RNAs as novel biomarkers in lung cancer and pulmonary tuberculosis (discovery cohort)
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PROVIDER: PRJNA625983 | ENA |
REPOSITORIES: ENA
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Project description:Peripheral blood non-canonical small non-coding RNAs as novel biomarkers in lung cancer and pulmonary tuberculosis (validation cohort)
| PRJNA625982 | ENA
Project description:One unmet challenge in current lung cancer diagnosis is to accurately differentiate lung cancer patients from those with other lung diseases with similar clinical symptoms and radiological features. Previous studies have reported cases of misdiagnosis for patients with lung cancer mimicking pulmonary tuberculosis (TB) or for TB patients with multiple lung nodules mimicking lung cancer progression, which is concerning for clinical practice in TB-endemic countries/regions. Here, we develop a molecular signature composed of non-canonical small non-coding RNAs in human peripheral blood mononuclear cells (PBMCs), including tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs). This signature consists of i) the tsRNAs derived from tRNA-Ala, tRNA-Asn, tRNA-Leu, tRNA-Lys, and tRNA-Tyr that are upregulated in the lung cancer patients relative to the healthy controls and patients with pulmonary TB, ii) the rsRNAs derived from rRNA-5S that are upregulated in the lung cancer patients but downregulated in TB patients relative to the controls, and iii) the ysRNAs originating from YRNA-RNY1 that are downregulated in the lung cancer patients but upregulated in the TB patients compared with the controls. This diagnostic signature discriminates between healthy controls, lung cancer patients, and pulmonary TB subjects with high accuracy in both the discovery and validation cohorts. We conclude that the PBMC tsRNAs, rsRNAs, and ysRNAs are informative for both screening for and discriminating between lung cancer and pulmonary TB.
2020-11-16 | GSE148861 | GEO
Project description:One unmet challenge in current lung cancer diagnosis is to accurately differentiate lung cancer patients from those with other lung diseases with similar clinical symptoms and radiological features. Previous studies have reported cases of misdiagnosis for patients with lung cancer mimicking pulmonary tuberculosis (TB) or for TB patients with multiple lung nodules mimicking lung cancer progression, which is concerning for clinical practice in TB-endemic countries/regions. Here, we develop a molecular signature composed of non-canonical small non-coding RNAs in human peripheral blood mononuclear cells (PBMCs), including tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNAs (rsRNAs), and YRNA-derived small RNAs (ysRNAs). This signature consists of i) the tsRNAs derived from tRNA-Ala, tRNA-Asn, tRNA-Leu, tRNA-Lys, and tRNA-Tyr that are upregulated in the lung cancer patients relative to the healthy controls and patients with pulmonary TB, ii) the rsRNAs derived from rRNA-5S that are upregulated in the lung cancer patients but downregulated in TB patients relative to the controls, and iii) the ysRNAs originating from YRNA-RNY1 that are downregulated in the lung cancer patients but upregulated in the TB patients compared with the controls. This diagnostic signature discriminates between healthy controls, lung cancer patients, and pulmonary TB subjects with high accuracy in both the discovery and validation cohorts. We conclude that the PBMC tsRNAs, rsRNAs, and ysRNAs are informative for both screening for and discriminating between lung cancer and pulmonary TB.
2020-11-16 | GSE148862 | GEO
Project description:Ovarian cancer is the leading cause of death in gynecological diseases, and has been considered as one of the most fatal cancers due to lack of reliable detection strategy in the early stage. Therefore the capability to detect the morbidity initiation with an sensitive and effective approach is one of the most desirable goals for curing ovarian cancer. In this study, we used microarray technology for salivary mRNA biomarkers discovery, and evaluated the performance and translational utilities of discovered markers from a clinical study using an independent sample cohort . We used microarrays to profile and compare the gene expressions between ovairan cancer patient and matched controls, and identified seven down-regulated genes after the validation study. To find salivary transcriptomic biomarkers for ovarian cancer, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled using Affymetrix HG-U133-Plus-2.0 array, and followed by t-test and fold-change analyses. The biomarker candidates selected from the microarray results were subjected to clinical validation using an independent sample cohort by RT-qPCR. The prediction power of biomarkers was analyzed by logistic regression approach
2011-05-12 | E-GEOD-29220 | biostudies-arrayexpress
Project description:Intra-individual stability of the urine miRNA transcriptome was examined by investigating longitudinal changes over time in a cohort of patients with localized prostate cancer. Using training and validation cohorts, urinary miRNA biomarkers are characterized and validated their utility to identify aggressive prostate cancer.
2019-10-24 | GSE104431 | GEO
Project description:Translation initiation generally occurs at AUG codons in eukaryotes although it has been shown that non-AUG or non-canonical translation initiation can also occur. However, the evidence for non-canonical translation initiation sites (TISs) is largely indirect and based on ribosome profiling studies. Here, using a strategy specifically designed to enrich N-termini of proteins, we demonstrate that many human proteins are translated at non-canonical TISs. The large majority of TISs that mapped to 5’ untranslated regions were non-canonical and led to N-terminal extension of annotated proteins or translation of upstream small open reading frames (uORF). There has been little controversy on whether the corresponding amino acid to the start codon is incorporated at TIS or methionine is still incorporated. Notably, methionine was incorporated at almost all non-canonical TISs identified in this study. Comparison of the TISs determined through mass spectrometry with ribosome profiling data revealed that about two-thirds of the novel annotations were indeed supported by ribosome profiling data. The sequence orthology analysis and relative translation frequency analysis of non-canonical TISs over canonical ones suggests that those non-canonical TISs are not leaky but they can have certain biological functions. Overall, this study provides evidence of protein translation initiation at non-canonical TISs and indicates that further studies are required for elucidation of functional implications of such non-canonical translation initiation.
2017-11-23 | PXD006633 | Pride
Project description:Malignant Hodgkin's lymphoma (HL) cells are characterized by constitutive activation of the canonical as well as the non-canonical NF-κB signaling cascades. We depleted subunit combinations corresponding to either canonical (p50/RelA) or non-canonical (p52/RelB) dimers in the HL cell line L-1236 and performed Affymetrix microarray analysis. Knockdown of p52/RelB affected the expression of a significantly higher number of genes than the knockdown of p50/RelA. The two sets of target genes presented a partial overlap, however they also revealed specific genes that are involved in distinct aspects of tumor biology. The knockdown of subunit combinations corresponding to either canonical (p50/RelA, experimental group 1) or non-canonical (p52/RelB, experimental group 2) NF-κB heterodimers were carried out in L-1236 cells. Two distinct siRNA sequences for every NF-κB subunit and two non-targeting siRNA sequences (control) were used for each experimental group. Experiments were performed in biological triplicates.
2016-02-18 | E-GEOD-64232 | biostudies-arrayexpress
Project description:Immunopeptides that are translated in cells and presented at the cell surface by major histocompatibility complex (MHC) mole-cules are important epitopes in basic Immunology and translational cancer immunotherapy. While most of the reported immuno-peptides are derived from protein coding sequence, the non-canonical peptides translated from “non-coding” regions are emerging and have attracted much attention in recent years. However, sensitive and accurate identification of such peptides remains a challenging task. Here we report an optimized approach integrating Ribo-seq and mass spectrometry to identify hundreds of non-canonical MHC-binding peptides. Three pipelines for analyzing Ribo-seq data were compared to generate small open reading frame (sORF) databases. Meanwhile, we have also combined bottom-up and de novo searching in proteomics data analysis and identified more immunopeptides. 7902 canonical and 308 non-canonical immunopeptides have been identified with selected ones vigorously validated. The present study provides a handy solution for identifying non-canonical MHC epitopes. The novel im-munopeptides resolving mechanisms of cancer antigen presentation, as well as applications in cancer immunotherapies.
2021-11-03 | PXD024415 | Pride
Project description:The androgen receptor splice variant 7 (AR-V7) lacks the ligand-binding domain; is detected with increased frequency in advanced prostate cancer and is postulated to be one crucial mechanism for disease progression and therapeutic resistance to androgen deprivation in castration–resistant prostate cancer (CRPC). Targeting AR-V7 or unique downstream targets could provide novel therapeutic approaches for CRPC. Here, we report that, independent of ligand, AR-V7 binds not only to the androgen-responsive element (ARE) sites inducing canonical AR signaling but also to non-canonical target sites where ligand-stimulated full-length AR (AR-FL) does not bind. These AR-V7 “solo” binding sites are mainly found at gene promoters and are co-occupied by a zinc-finger transcription factor ZFX and the co-activator BRD4, both of which physically interact with AR-V7. Consequently, AR-V7 not only recapitulates AR-FL action without androgen but uniquely regulates transcripts correlating with AR-V7 expression in the TCGA prostate cancer cohort. Mechanistically, ZFX appears to function as a pioneer factor for AR-V7 at solo-binding sites and BRD4 inhibitors but not anti-androgens suppress AR-V7 action at solo-binding sites as well as AR-V7-dependent growth. Additionally, knockdown of ZFX, or two downstream targets uniquely co-activated by AR-V7 (ZNF32 and FZD6), also suppressed growth of AR-V7-dependent CRPC cells. AR-V7 directly activated genes differentiate tumor from normal prostate tissues and predict poor prognosis in patients. Thus AR-V7 has both canonical and non-canonical regulatory functions in CRPC, which may provide new therapeutic avenues.
2018-10-02 | GSE94013 | GEO
Project description:The non-coding RNome after splenectomy (cohort A)
| PRJNA551974 | ENA