Abstract:Cancer is an extremely diverse and complex disease that results from various genetic and epigenetic changes such as DNA copy-number variations, mutations, and aberrant mRNA and/or protein expression caused by abnormal transcriptional regulation. The expression profiles of certain microRNAs (miRNAs) and messenger RNAs (mRNAs) are closely related to cancer progression stages. In the past few decades, DNA microarray and next-generation sequencing techniques have been widely applied to identify miRNA and mRNA sign… Show more
“…MicroRNAs demonstrate exceptional stability even in difficult biological samples such as formalin-fixed paraffin-embedded tissue sections, blood, and urine [30, 31] and have been used as prognostic biomarkers in a number of cancers [32]. Moreover, several recent reports suggest that DCLK1 regulates EMT through a miRNA-dependent mechanism, which has also been confirmed in pancreatic and colon cancer using tumor xenograft models [25, 33].…”
DCLK1 is a gastrointestinal (GI) tuft cell kinase that has been investigated as a biomarker of cancer stem-like cells in colon and pancreatic cancers. However, its utility as a biomarker may be limited in principle by signal instability and dilution in heterogeneous tumors, where the proliferation of diverse tumor cell lineages obscures the direct measurement of DCLK1 activity. To address this issue, we explored the definition of a microRNA signature as a surrogate biomarker for DCLK1 in cancer stem-like cells. Utilizing RNA/miRNA sequencing datasets from the Cancer Genome Atlas, we identified a surrogate 15-miRNA expression signature for DCLK1 activity across several GI cancers, including colon, pancreatic and stomach cancers. Notably, Cox regression and Kaplan-Meier analysis demonstrated that this signature could predict the survival of patients with these cancers. Moreover, we identified patient subgroups that predicted the clinical utility of this DCLK1 surrogate biomarker. Our findings greatly strengthen the clinical significance for DCLK1 expression across GI cancers. Further, they provide an initial guidepost toward the development of improved prognostic biomarkers or companion biomarkers for DCLK1-targeted therapies to eradicate cancer stem-like cells in these malignancies.
“…MicroRNAs demonstrate exceptional stability even in difficult biological samples such as formalin-fixed paraffin-embedded tissue sections, blood, and urine [30, 31] and have been used as prognostic biomarkers in a number of cancers [32]. Moreover, several recent reports suggest that DCLK1 regulates EMT through a miRNA-dependent mechanism, which has also been confirmed in pancreatic and colon cancer using tumor xenograft models [25, 33].…”
DCLK1 is a gastrointestinal (GI) tuft cell kinase that has been investigated as a biomarker of cancer stem-like cells in colon and pancreatic cancers. However, its utility as a biomarker may be limited in principle by signal instability and dilution in heterogeneous tumors, where the proliferation of diverse tumor cell lineages obscures the direct measurement of DCLK1 activity. To address this issue, we explored the definition of a microRNA signature as a surrogate biomarker for DCLK1 in cancer stem-like cells. Utilizing RNA/miRNA sequencing datasets from the Cancer Genome Atlas, we identified a surrogate 15-miRNA expression signature for DCLK1 activity across several GI cancers, including colon, pancreatic and stomach cancers. Notably, Cox regression and Kaplan-Meier analysis demonstrated that this signature could predict the survival of patients with these cancers. Moreover, we identified patient subgroups that predicted the clinical utility of this DCLK1 surrogate biomarker. Our findings greatly strengthen the clinical significance for DCLK1 expression across GI cancers. Further, they provide an initial guidepost toward the development of improved prognostic biomarkers or companion biomarkers for DCLK1-targeted therapies to eradicate cancer stem-like cells in these malignancies.
“…Ribonucleic acid (RNA) biomarkers comprising different coding and noncoding transcriptome such as messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) are becoming progressively crucial in understanding disease diagnosis and prognosis due to their recognized physiological role in gene expression and regulation . Dysregulation of these RNA biomarkers is involved in the initiation and progression of several diseases including cancers .…”
Ribonucleic acids (RNAs) are considered as effective and minimally invasive biomarkers for disease diagnosis and prognosis due to their critical role in the regulation of different cellular processes. Over the past several years, the rapid progress in RNA biomarker research has resulted in the development of a large number of high‐performance RNA‐detection methods. Most of these methods are based on molecular‐biology techniques such as quantitative reverse transcription polymerase chain reaction (RT‐qPCR), microarrays, and RNA sequencing. In recent years, considerable attention has also been dedicated to developing RNA biosensors, exploiting micro‐ and nanofabrication technologies, and various readout strategies, including electrochemical and optical transducers. Here, the recent developments of RNA biosensors are concisely reviewed with a special emphasis on electrochemical‐detection approaches. The following points are also highlighted: i) all the types of clinically relevant RNAs (mRNAs, miRNAs, lncRNAs) and their diagnostic and prognostic potential in cancer are outlined, ii) major challenges associated with current techniques are identified, followed by a critical analysis of how these challenges have been addressed by different biosensing approaches, and iii) the current requirements that still need to be met for effective screening of RNA biomarkers in both research and clinical settings.
“…Abnormal expression of mRNAs has been widely demonstrated in human cancers, and researches suggested that the dysregulated mRNAs emerged as critical roles in various biological functions associated with progression of cancers. 27,28 However, only a few reports have identified mRNA profiles in T-cell lymphoma by microarray analysis. 16 In this study, we identified mRNAs in T-cell lymphomas from GEO database, which may be related to diagnosis, classification, medical treatment sensitivity, and tumor microenvironment in T-cell lymphomas.…”
Our findings uncovered aberrantly expressed genes and a complex RNA signal network in T-cell lymphomas and indicated cancer-related pathways involved in disease initiation and progression, providing a new insight for biotargeted therapy in T-cell lymphomas.
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