Exosomal miRNAs species in the blood of small cell and non-small cell lung cancer patients

Poroyko, Valeriy; Mirzapoiazova, Tamara; Nam, Arin; Mambetsariev, Isa; Mambetsariev, Bolot; Wu, Xiwei; Husain, Aliya N.; Vokes, Everett E.; Wheeler, Deric L.; Salgia, Ravi

doi:10.18632/oncotarget.24857

Cited by 39 publications

(38 citation statements)

References 68 publications

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“…On the other hand, in SCLC, Nishikawa et al showed that miR-375 was significantly increased in SCLC cell lines as opposed to those of different histologic types when they examined the miRNA expression profiles on lung cell lines [182]. Moreover, a recent cohort study has identified 13 miRNAs able to accurately differentiate between SCLC and NSCLC patients, 3 of which, namely hsa-miR-331-5p, hsa-miR-451a and hsa-miR-363-3p, reaching sensitivity and specificity of 100% [183].…”

Section: Mirnas In Distinguishing Cancer Subtypesmentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

927

583

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MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

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Section: Mirnas In Distinguishing Cancer Subtypesmentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

927

583

View full text Add to dashboard Cite

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“…Another study identified 17 miRNA species in the exosomes of the blood that are differentially expressed in cancer (both NSCLC and SCLC) and controls (27). The potential use of ctDNA for early detection of other cancers has also been reported (29,30).…”

Section: Discussionmentioning

confidence: 99%

Multi-Center Study of Resectable Lung Lesions by Ultra-Deep Sequencing of Targeted Genes in Plasma Cell-Free DNA to Assess Nodule Malignancy and Detect Lung Cancers

Xie

X²,

et al. 2018

Preprint

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BACKGROUND Early detection of lung cancer to allow curative treatment remains challenging.Cell-free circulating tumor DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery. METHODS The multi-center clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white blood cell genomic DNA (gDNA) and tumor tissue gDNA of each patient were analyzed by ultra-deep sequencing to an average of 35,000X of the coding regions of 65 lung cancer-related genes.RESULTS The cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64% of the cancer patients is at Stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91% and specificity of 88%.When ctDNA assay was used as the test, the sensitivity was 69% and specificity 96%. As for the lung cancer patients, the assay detected 63%, 83%, 94% and 100%, for Stage I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80% at a specificity of 99%. 29 out of the 65 genes harbored mutations in the lung cancer patients with the largest number found in TP53 (30% plasma and 62% tumor tissue samples) and EGFR (20% and 40%, respectively).CONCLUSION Plasma ctDNA was analyzed in lung nodule assessment and early cancer detection while an algorithm combining clinical information enhanced the test performance.

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“…When the tissue obtained is sufficient for a histopathological analysis, a definitive diagnosis is more likely. However, even if a sufficient biopsy can be obtained, it is an unreliable method in cases of heterogeneous and continuously evolving tumors, because it increases the patient's risk and discomfort when collecting repetitive samples [21,22].…”

Section: Lung Cancer Diagnosismentioning

confidence: 99%

Current advances in early detection, residual disease monitoring and treatment response in lung cancer: liquid biopsy

Güven¹,

Gülhan²

2018

Curr Thorac Surg

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Lung cancer exhibits the highest mortality rate of all malignant tumors, and only a minority of non-small cell lung cancer (NSCLC) patients are diagnosed with localized, early stage tumors. Unfortunately, NSCLC is usually detected at advanced and inoperable stages. Tumor biomarkers can detect early stage lung cancer independently or in combination with low-dose computed tomography-based screening techniques. A liquid biopsy is a noninvasive modality for the pathological and molecular characterization of cancer, and it can be isolated from bodily fluids. There are a variety of biological elements that can be isolated from the peripheral blood, such as exosomes, circulating cell-free (tumor) DNA, circulating tumor cells, and microRNA. A liquid biopsy can be used to detect somatic mutations before treatment and dynamically during treatment, and to monitor the treatment response. It can also be used for minimal residual disease quantification, and to determine the emergence of therapy resistance. Despite the numerous research studies showing successful results, clinically available lung cancer biomarkers do not have sufficiently high specificity and sensitivity for widespread use. Therefore, universal experimental and therapeutic research regarding advanced molecular diagnostics has become necessary.

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Exosomal miRNAs species in the blood of small cell and non-small cell lung cancer patients

Cited by 39 publications

References 68 publications

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Multi-Center Study of Resectable Lung Lesions by Ultra-Deep Sequencing of Targeted Genes in Plasma Cell-Free DNA to Assess Nodule Malignancy and Detect Lung Cancers

Current advances in early detection, residual disease monitoring and treatment response in lung cancer: liquid biopsy

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