Increased DCLK1 correlates with the malignant status and poor outcome in malignant tumors: a meta-analysis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Doublecortin-like kinase 1 (DCLK1) has been found to be involved in malignant biological behavior of cancers and poor prognosis of cancer patients. The aim of this meta-analysis was to systematically clarify the relationships between expression level of DCLK1 and clinicopathological characteristics in tumors and assess its clinical value in cancer diagnosis and prognosis. 18 eligible studies with a total of 2660 patients were identified by searching the electronic bibliographic databases. Pooled results showed that DCLK1 was highly expressed in tissues from cancer patients compared to normal tissues (OR, 10.00), and overexpression of DCLK1 was significantly correlated with advanced clinical stage (OR, 2.48), positive lymph node metastasis (OR, 2.18), poorly differentiated cancers (OR, 1.83) and poor overall survival (HR, 2.15). The overall combined sensitivity and specificity for DCLK1 in distinguishing malignant tumors were 0.58 and 0.90, respectively. The mean diagnostic odds ratio was 12.70, and the corresponding area under the summary receiver operating characteristic curve was 0.78. In summary, our study indicated that DCLK1 could be a risk factor for development of malignant tumors and may serve as a promising diagnostic and prognostic biomarker for malignant tumors.

Related collections

Most cited references 29

Record: found
Abstract: found
Article: not found

Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations.

L E Moses, D. Shapiro, B Littenberg (1993)

We consider how to combine several independent studies of the same diagnostic test, where each study reports an estimated false positive rate (FPR) and an estimated true positive rate (TPR). We propose constructing a summary receiver operating characteristic (ROC) curve by the following steps. (i) Convert each FPR to its logistic transform U and each TPR to its logistic transform V after increasing each observed frequency by adding 1/2. (ii) For each study calculate D = V - U, which is the log odds ratio of TPR and FPR, and S = V + U, an implied function of test threshold; then plot each study's point (Si, Di). (iii) Fit a robust-resistant regression line to these points (or an equally weighted least-squares regression line), with V - U as the dependent variable. (iv) Back-transform the line to ROC space. To avoid model-dependent extrapolation from irrelevant regions of ROC space we propose defining a priori a value of FPR so large that the test simply would not be used at that FPR, and a value of TPR so low that the test would not be used at that TPR. Then (a) only data points lying in the thus defined north-west rectangle of the unit square are used in the data analysis, and (b) the estimated summary ROC is depicted only within that subregion of the unit square. We illustrate the methods using simulated and real data sets, and we point to ways of comparing different tests and of taking into account the effects of covariates.

0 comments Cited 337 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis.

Kelechi E Nnoaham, Aileen Clarke (2008)

To explore the association between low serum vitamin D and risk of active tuberculosis in humans. Systematic review and meta-analysis. Observational studies published between 1980 and July 2006 (identified through Medline) that examined the association between low serum vitamin D and risk of active tuberculosis. For the review, seven papers were eligible from 151 identified in the search. The pooled effect size in random effects meta-analysis was 0.68 with 95% CI 0.43-0.93. This 'medium to large' effect represents a probability of 70% that a healthy individual would have higher serum vitamin D level than an individual with tuberculosis if both were chosen at random from a population. There was little heterogeneity between the studies. Low serum vitamin D levels are associated with higher risk of active tuberculosis. Although more prospectively designed studies are needed to firmly establish the direction of this association, it is more likely that low body vitamin D levels increase the risk of active tuberculosis. In view of this, the potential role of vitamin D supplementation in people with tuberculosis and hypovitaminosis D-associated conditions like chronic kidney disease should be evaluated.

0 comments Cited 195 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

DCLK1 Regulates Pluripotency and Angiogenic Factors via microRNA-Dependent Mechanisms in Pancreatic Cancer

Sripathi Sureban, Randal May, Dongfeng Qu … (2013)

Stem cell pluripotency, angiogenesis and epithelial-mesenchymal transition (EMT) have been shown to be significantly upregulated in pancreatic ductal adenocarcinoma (PDAC) and many other aggressive cancers. The dysregulation of these processes is believed to play key roles in tumor initiation, progression, and metastasis, and is contributory to PDAC being the fourth leading cause of cancer-related deaths in the US. The tumor suppressor miRNA miR-145 downregulates critical pluripotency factors and oncogenes and results in repressed metastatic potential in PDAC. Additionally, the miR-200 family regulates several angiogenic factors which have been linked to metastasis in many solid tumors. We have previously demonstrated that downregulation of DCLK1 can upregulate critical miRNAs in both in vitro and in vivo cancer models and results in downregulation of c-MYC, KRAS, NOTCH1 and EMT-related transcription factors. A recent report has also shown that Dclk1 can distinguish between normal and tumor stem cells in Apc min/+ mice and that ablation of Dclk1+ cells resulted in regression of intestinal polyps without affecting homeostasis. Here we demonstrate that the knockdown of DCLK1 using poly(lactide-co-glycolide)-encapsulated-DCLK1-siRNA results in AsPC1 tumor growth arrest. Examination of xenograft tumors revealed, (a) increased miR-145 which results in decreased pluripotency maintenance factors OCT4, SOX2, NANOG, KLF4 as well as KRAS and RREB1; (b) increased let-7a which results in decreased pluripotency factor LIN28B; and (c) increased miR-200 which results in decreased VEGFR1, VEGFR2 and EMT-related transcription factors ZEB1, ZEB2, SNAIL and SLUG. Specificity of DCLK1 post-transcriptional regulation of the downstream targets of miR-145, miR-200 and let-7a was accomplished utilizing a luciferase-based reporter assay. We conclude that DCLK1 plays a significant master regulatory role in pancreatic tumorigenesis through the regulation of multiple tumor suppressor miRNAs and their downstream pro-tumorigenic pathways. This novel concept of targeting DCLK1 alone has several advantages over targeting single pathway or miRNA-based therapies for PDAC.

0 comments Cited 69 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 21 November 2017

Publication date (Electronic): 10 August 2017

Volume: 8

Issue: 59

Pages: 100545-100557

Affiliations

¹ Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China

Author notes

Correspondence to: Manxiang Li, manxiangli@ 123456hotmail.com

Article

Publisher ID: 20129

DOI: 10.18632/oncotarget.20129

PMC ID: 5725042

SO-VID: 3b64e2e9-ce66-47a4-a251-5e0a166acec8

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Increased DCLK1 correlates with the malignant status and poor outcome in malignant tumors: a meta-analysis

Read this article at

Abstract

Related collections

Karger: Oncology

Most cited references 29

Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations.

Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis.

DCLK1 Regulates Pluripotency and Angiogenic Factors via microRNA-Dependent Mechanisms in Pancreatic Cancer

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 165

Cited by 5

Most referenced authors 934