VDR mRNA overexpression is associated with worse prognostic factors in papillary thyroid carcinoma

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

The purpose of this study was to assess the relationship between vitamin D receptor gene ( VDR) expression and prognostic factors in papillary thyroid cancer (PTC). mRNA sequencing and somatic mutation data from The Cancer Genome Atlas (TCGA) were analyzed. VDR mRNA expression was compared to clinicopathologic variables by linear regression. Tree-based classification was applied to find cutoff and patients were split into low and high VDR group. Logistic regression, Kaplan–Meier analysis, differentially expressed gene (DEG) test and pathway analysis were performed to assess the differences between two VDR groups. VDR mRNA expression was elevated in PTC than that in normal thyroid tissue. VDR expressions were high in classic and tall-cell variant PTC and lateral neck node metastasis was present. High VDR group was also associated with classic and tall cell subtype, AJCC stage IV and lower recurrence-free survival. DEG test reveals that 545 genes were upregulated in high VDR group. Thyroid cancer-related pathways were enriched in high VDR group in pathway analyses. VDR mRNA overexpression was correlated with worse prognostic factors such as subtypes of papillary thyroid carcinoma that are known to be worse prognosis, lateral neck node metastasis, advanced stage and recurrence-free survival.

Related collections

Most cited references 19

Record: found
Abstract: found
Article: not found

Genetics and biology of vitamin D receptor polymorphisms.

André G. Uitterlinden, Yue Fang, Joyce B J van Meurs … (2004)

The vitamin D endocrine system is involved in a wide variety of biological processes including bone metabolism, modulation of the immune response, and regulation of cell proliferation and differentiation. Variations in this endocrine system have, thus, been linked to several common diseases, including osteoarthritis (OA), diabetes, cancer, cardiovascular disease, and tuberculosis. Evidence to support this pleiotropic character of vitamin D has included epidemiological studies on circulating vitamin D hormone levels, but also genetic epidemiological studies. Genetic studies provide excellent opportunities to link molecular insights with epidemiological data and have therefore gained much interest. DNA sequence variations, which occur frequently in the population, are referred to as "polymorphisms" and can have modest and subtle but true biological effects. Their abundance in the human genome as well as their high frequencies in the human population have made them targets to explain variation in risk of common diseases. Recent studies have indicated many polymorphisms to exist in the vitamin D receptor (VDR) gene, but the influence of VDR gene polymorphisms on VDR protein function and signaling is largely unknown. So far, three adjacent restriction fragment length polymorphisms for BsmI, ApaI, and TaqI, respectively, at the 3' end of the VDR gene have been the most frequently studied. Because these polymorphisms are probably nonfunctional, linkage disequilibrium with one or more truly functional polymorphisms elsewhere in the VDR gene is assumed to explain the associations observed. Research is therefore focussed on documenting additional polymorphisms across the VDR gene to verify this hypothesis and on trying to understand the functional consequences of the variations. Substantial progress has been made that will deepen our understanding of variability in the vitamin D endocrine system and might find applications in risk assessment of disease and in predicting response-to-treatment.

0 comments Cited 393 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes.

Yanfang Guo, Peng Xiao, Shufeng Lei … (2008)

A key assumption in studying mRNA expression is that it is informative in the prediction of protein expression. However, only limited studies have explored the mRNA-protein expression correlation in yeast or human tissues and the results have been relatively inconsistent. We carried out correlation analyses on mRNA-protein expressions in freshly isolated human circulating monocytes from 30 unrelated women. The expressed proteins for 71 genes were quantified and identified by 2-D electrophoresis coupled with mass spectrometry. The corresponding mRNA expressions were quantified by Affymetrix gene chips. Significant correlation (r=0.235, P<0.0001) was observed for the whole dataset including all studied genes and all samples. The correlations varied in different biological categories of gene ontology. For example, the highest correlation was achieved for genes of the extracellular region in terms of cellular component (r=0.643, P<0.0001) and the lowest correlation was obtained for genes of regulation (r=0.099, P=0.213) in terms of biological process. In the genome, half of the samples showed significant positive correlation for the 71 genes and significant correlation was found between the average mRNA and the average protein expression levels in all samples (r=0.296, P<0.01). However, at the study group level, only five studied genes had significant positive correlation across all the samples. Our results showed an overall positive correlation between mRNA and protein expression levels. However, the moderate and varied correlations suggest that mRNA expression might be sometimes useful, but certainly far from perfect, in predicting protein expression levels.

0 comments Cited 140 times – based on 0 reviews      Review now

Record: found
Abstract: found
Article: not found

The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature.

Kim Köstner, Nicole Denzer, Cornelia S L Müller … (2009)

In recent years, the relevance of vitamin D receptor (VDR) gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies. It has been hypothesized that VDR polymorphisms may influence both the risk of cancer occurrence and prognosis. However, studies investigating the associations between specific VDR polymorphisms and cancer often show controversial results. We have now performed a systematic review of the literature to analyse the relevance of VDR polymorphisms for individual malignancies, including cancer of the skin, prostate, breast, colon, ovary, kidney and bladder. An analysis of studies evaluating the association between vitamin D receptor gene polymorphisms Fok1, Bsm1, Taq1, Apa1, and Cdx2, poly (A) and Bgl1 as well as some haplotype combinations and cancer risk has been performed. Data were extracted from PubMed using the key words VDR polymorphism in combination with breast cancer, prostate cancer, skin cancer, colorectal cancer, ovarian cancer, renal cell carcinoma or bladder cancer. This analysis was performed with the intent of giving an up-to-date overview of all data concerning the relevance of VDR polymorphisms for cancer. Obviously, at present it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer occurrence. It seems probable that interactions with other factors such as calcium and vitamin D intake, 25(OH)D plasma levels and UV radiation exposure play a decisive role in cancer occurrence and should not be underestimated. Other risk factors such as obesity, smoking status, parity status, energy intake and others are also frequently mentioned as being more or less important for carcinogenesis depending on the VDR genotype. Moreover, it is often noticed that the same VDR polymorphism has a different effect depending on the type of cancer, or may be only decisive for more or less aggressive staging of the tumour. Significant associations with VDR polymorphisms have been reported in cancer of the breast (Fok1, Bsm1, Taq1, Apa1, poly (A)), prostate (Fok1, Bsm1, Taq1, poly (A)), skin (Fok1, Bsm1, A-1210), colorectum (Fok1, Bsm1), ovary (Fok1, Apa1) and bladder (Fok1), and in renal cell carcinoma (Taq1, Apa1). However, conflicting data have been reported for most malignancies. After careful evaluation of the actual literature, it can be summarized that data indicating an association of VDR polymorphisms and cancer risk are strongest for breast cancer (Bsm1, Fok1), prostate cancer (Fok1) and malignant melanoma (MM) (Fok1). Data indicating an association of VDR polymorphisms and cancer prognosis are strongest for prostate cancer (Fok1), breast cancer (Bsm1, Taq1), MM (Bsm1) and renal cell carcinoma (Taq1).

0 comments Cited 83 times – based on 0 reviews      Review now

All references

Author and article information

Journal

Journal ID (nlm-ta): Endocr Connect

Journal ID (iso-abbrev): Endocr Connect

Journal ID (hwp): EC

Title: Endocrine Connections

Publisher: Bioscientifica Ltd (Bristol )

ISSN (Electronic): 2049-3614

Publication date Collection: April 2017

Publication date (Electronic): 21 February 2017

Volume: 6

Issue: 3

Pages: 172-178

Affiliations

[1 ]Department of Surgery Seoul National University Bundang Hospital, Seongnam-si, Korea

[2 ]Department of Surgery Seoul National University Hospital and College of Medicine, Seoul, Korea

[3 ]Department of Surgery Seoul National University Boramae Hospital, Seoul, Korea

Author notes

Correspondence should be addressed to K E Lee; Email: kyueunlee@ 123456snu.ac.kr

[*]

(J Y Choi and J W Yi contributed equally as a co-first authors)

Article

Publisher ID: EC170001

DOI: 10.1530/EC-17-0001

PMC ID: 5424767

PubMed ID: 28223310

SO-VID: db41e89d-8b4a-49a8-bdb8-3cf9072da0a6

License:

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License..

The flagship journal of the Society for Endocrinology. Learn more

VDR mRNA overexpression is associated with worse prognostic factors in papillary thyroid carcinoma

Read this article at

Abstract

Related collections

Bioscientifica Open Endocrinology

Most cited references 19

Genetics and biology of vitamin D receptor polymorphisms.

How is mRNA expression predictive for protein expression? A correlation study on human circulating monocytes.

The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 366

Cited by 8

Most referenced authors 1,605