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Peripheral blood non-canonical small non-coding RNAs as novel biomarkers in lung cancer and pulmonary tuberculosis (discovery cohort)

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE148861 | GEO | 2020/11/16

REPOSITORIES: GEO

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Peripheral blood non-canonical small non-coding RNAs as novel biomarkers in lung cancer and pulmonary tuberculosis (validation cohort)

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

PANDORA-seq: expanding the small RNA repertoire by overcoming RNA modifications

Project description:Small non-coding RNAs (sncRNAs) are key molecules regulating gene expression. High-throughput RNA-seq greatly advanced sncRNA discovery; however, traditional cDNA library construction protocols generate biased sequencing results, in part due to RNA modifications that interfere with adapter ligation and reverse transcription processes, preventing the detection of sncRNAs bearing these modifications. Here, we present PANDORA-seq (Panoramic RNA Display by Overcoming RNA modification Aborted Sequencing), employing a combination of enzymatic treatments to remove key RNA modifications that block adapter ligation and reverse transcription during cDNA library construction. PANDORA-Seq enables the discovery of thousands of modified sncRNAs previously undetected, mostly tRNA-derived small RNAs (tsRNAs) and rRNA-derived small RNAs (rsRNAs), which are tissue/cell-specifically detected across mouse brain, liver, spleen, sperm, mouse and human embryonic stem cells, and HeLa cells. Moreover, PANDORA-Seq reveals dynamic changes of tsRNAs and rsRNAs during reprogramming of induced pluripotent stem cells (iPSCs), pointing to future investigations on their potential regulatory functions.

2021-02-16 | GSE144666 | GEO

Human whole blood microarray study to compare patients with tuberculosis, sarcoidosis, pneumonia, and lung cancer (training)

Project description:This study used whole blood transcriptional signatures from patients with tuberculosis compared to those with similar pulmonary diseases, sarcoidosis, pneumonia and primary lung cancer. TB and sarcoidosis had similar signatures that were distinct from pneumonia and lung cancer. There were 16 TB, 25 sarcoidosis, 8 pneumonia, 8 lung cancer and 38 healthy controls

2013-10-31 | E-GEOD-42830 | biostudies-arrayexpress

Human whole blood microarray study to compare patients with tuberculosis, sarcoidosis, pneumonia, and lung cancer (test)

Project description:This study used whole blood transcriptional signatures from patients with tuberculosis compared to those with similar pulmonary diseases, sarcoidosis, pneumonia and primary lung cancer. TB and sarcoidosis had similar signatures that were distinct from pneumonia and lung cancer. There were 11 TB, 25 sarcoidosis, 6 pneumonia, 8 lung cancer and 52 healthy controls

2013-10-31 | E-GEOD-42826 | biostudies-arrayexpress

Identification of small noncoding RNAs as sperm quality biomarkers for in vitro fertilization

Project description:We investigated differentially expressed sncRNAs in human sperm as candidate markers for evaluating sperm quality during IVF. We demonstrated that differentially expressed tsRNAs, rsRNAs and miRNAs are linked to sperm quality according to embryo quality, even though these sperm samples were all considered normal by the traditional semen-parameter assessment. Therefore, the sncRNAs, especially tsRNAs and rsRNAs, may be potential clinical biomarkers for the assessment of sperm quality in IVF.

2019-02-21 | GSE110190 | GEO

Circulating tRNA-derived small RNAs (tsRNAs) signature for the diagnosis and prognosis of breast cancer

Project description:Liquid biopsy is noninvasive and convenient to detect cancer-derived materials in blood or other body fluids. The aim of this study was to identify tRNA-derived small RNAs (tsRNAs) in plasma that could distinguish patients with breast cancer (BC) from healthy controls. Basing on high-throughput sequencing, 15 significantly upregulated tsRNAs were selected and assessed in cell supernatants and cell lines. 6 tsRNAs were identified and verified in a large cohort of 120 patients with BC and 112 healthy controls. tRF-Arg-CCT-017, tRF-Gly-CCC-001 and tiRNA-Phe-GAA-003 could serve as novel diagnostic biomarkers. Meanwhile, tRF-Arg-CCT-017 and tiRNA-Phe-GAA-003 could also act as prognostic biomarkers. Target genes of these tsRNAs were related to the development of cancer. These results suggest that specific tsRNAs in plasma might serve as diagnostic and prognostic biomarkers of BC.

2020-10-08 | GSE158945 | GEO

Human whole blood microarray study to compare patients with tuberculosis, sarcoidosis, pneumonia, and lung cancer (training)

2013-10-31 | GSE42830 | GEO

Human whole blood microarray study to compare patients with tuberculosis, sarcoidosis, pneumonia, and lung cancer (test)

2013-10-31 | GSE42826 | GEO

Identification of RNA helicases that mediate processing of tRNAs into distinct tRNA fragments by LC-MS/MS.

Project description:Specific environmental insults cause the limited fragmentation of transfer RNAs (tRNAs) into tRNA-derived small RNAs (tsRNAs), which have been implicated in a wide range of biological processes. tRNA fragmentation results from endonucleolytic activities targeting single-stranded tRNA regions. However, how a tRNA with a single hydrolyzed phosphodiester bond in the anticodon loop (‘nicked’ tRNA) gives rise to distinct tsRNAs remains poorly understood. By utilizing biochemical fractionation of tsRNA-containing ribonucleoprotein complexes (RNPs) coupled with LC-MS/MS, we identified several RNA helicase enzymes that represent putative tRNA/tsRNA processing enzymes. Furthermore, a combination of biochemical and computational approaches revealed that specific RNA helicases indeed bind specific tRNAs with high affinity, as well as process nicked tRNAs into individual tsRNAs. In summary, these findings reveal that tRNA-derived duplexes can be substrates of well-known RNA helicases, thereby expanding their potential for cellular function to the creation of individual tsRNAs during the cellular stress response.

2023-01-09 | PXD029869 | Pride

Gene expression profiles of caseous human pulmonary TB granulomas derived from TB patients

Project description:Most individuals infected with Mycobacterium tuberculosis can control the infection by forming and maintaining TB granulomas at the local infection foci. However, when the chronic infection (also known as latency) becomes active, the caseous center of TB granuloma enlarges, and it liquefies and cavitates, ultimately releasing bacilli into airway. Deciphering how genes are regulated within TB granulomas will help to understand the granuloma biology. Therefore, we performed genome-wide microarray on caseous human pulmonary TB granulomas and compared with normal lung tissues. Laser capture microdissection (LCM) was used to dissect out caseous granulomas from TB patients' lung tissues, excluding uninvolved areas. Total RNA were isolated from LCM-derived materials and used for microarray. As a control, parenchyma from normal lung tissues was prepared in the same manner as caseous granulomas. Sample GSM501252, Caseum 2-C, is missing a CEL file.

2010-06-08 | E-GEOD-20050 | biostudies-arrayexpress

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