Associations of cholesterol and vitamin D metabolites with the risk for development of high grade colorectal cancer

Vladimirov, Sandra; Zeljković, Aleksandra; Gojković, Tamara; Miljković, Milica; Stefanović, Aleksandra; Zeljkovic, Dejan; Trifunović, Bratislav; Spasojević‐Kalimanovska, Vesna

doi:10.2478/jomb-2019-0047

“…Results of a study conducted by our research group also demonstrated lower HDL-C levels in CRC patients [173]. However, we observed that the relative content of cholesterol precursors on HDL particles is higher when compared to healthy controls (unpublished data).…”

Section: Hdl and Cholesterol Trafficking In Crcsupporting

confidence: 66%

“…Still, it remains to be investigated to what extent the increased functionality of SR-B1 contributes to the observed lowering of plasma HDL-C levels. Results of a study conducted by our research group also demonstrated lower HDL-C levels in CRC patients [ 173 ]. However, we observed that the relative content of cholesterol precursors on HDL particles is higher when compared to healthy controls (unpublished data).…”

Section: Hdl and Cholesterol Trafficking In Crcmentioning

confidence: 75%

Revealing the Role of High-Density Lipoprotein in Colorectal Cancer

Zeljković

¹

,

Mihajlović

²

,

Gojković

³

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a highly prevalent malignancy with multifactorial etiology, which includes metabolic alterations as contributors to disease development. Studies have shown that lipid status disorders are involved in colorectal carcinogenesis. In line with this, previous studies have also suggested that the serum high-density lipoprotein cholesterol (HDL-C) level decreases in patients with CRC, but more recently, the focus of investigations has shifted toward the exploration of qualitative properties of HDL in this malignancy. Herein, a comprehensive overview of available evidences regarding the putative role of HDL in CRC will be presented. We will analyze existing findings regarding alterations of HDL-C levels but also HDL particle structure and distribution in CRC. In addition, changes in HDL functionality in this malignancy will be discussed. Moreover, we will focus on the genetic regulation of HDL metabolism, as well as the involvement of HDL in disturbances of cholesterol trafficking in CRC. Finally, possible therapeutic implications related to HDL will be presented. Given the available evidence, future studies are needed to resolve all raised issues concerning the suggested protective role of HDL in CRC, its presumed function as a biomarker, and eventual therapeutic approaches based on HDL.

show abstract

“…Among them, fourteen vitamin D-related genes (CYP24A1, TGFB1, IGFBP2, IGFBP3, VGF, AGAP2, DENND6B, LRRC8A, BCL6, FCER2, ELL, CD36, AGPAT1, and TMCO6) were associated with high risk and three (NCOA7, GSR, and MPC1) were identified as protective factors. Researches have demonstrated that dysregulation of vitamin D-related pathways contributes to the pathogenesis of CRC ( Dou et al, 2016 ; Sluyter, Manson & Scragg, 2021 ; Vladimirov et al, 2020 ). Studies have demonstrated that some vitamin D-related genes of this signature are involved in metabolism, including AGPAT1, VGF, and MPC1 ( Agarwal et al, 2017 ; Stephens et al, 2017 ; You, Lee & Roh, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Vitamin D-related gene signature to predict colorectal cancer prognosis

Bu

¹

,

Huang

²

,

Li

³

et al. 2021

PeerJ

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most common malignant carcinomas worldwide with poor prognosis, imposing an increasingly heavy burden on patients. Previous experiments and epidemiological studies have shown that vitamin D and vitamin D-related genes play a vital role in CRC. Therefore, we aimed to construct a vitamin D-related gene signature to predict prognosis in CRC. The CRC data from The Cancer Genome Atlas (TCGA) was performed as the training set. A total of 173 vitamin D-related genes in the TCGA CRC dataset were screened, and 17 genes associated with CRC prognosis were identified from them. Then, a vitamin D-related gene signature consisting of those 17 genes was established by univariate and multivariate Cox analyses. Moreover, four external datasets (GSE17536, GSE103479, GSE39582, and GSE17537) were used as testing set to validate the stability of this signature. The high-risk group presented a significantly poorer overall survival than low-risk group in both of training set and testing sets. Besides, the areas under the curve (AUCs) for signature on OS in training set at 1, 3, and 5 years were 0.710, 0.708, 0.710 respectively. The AUCs of the ROC curve in GSE17536 for 1, 3, and 5 years were 0.649, 0.654, and 0.694. These results indicated the vitamin D-related gene signature model could effectively predict the survival status of CRC patients. This vitamin D-related gene signature was also correlated with TNM stage in CRC clinical parameters, and the higher risk score from this model was companied with higher clinical stage. Furthermore, the high accuracy of this prognostic signature was validated and confirmed by nomogram model. In conclusion, we have proposed a novel vitamin D-related gene model to predict the prognosis of CRC, which will help provide new therapeutic targets and act as potential prognostic biomarkers for CRC.

show abstract

“…Among them, fourteen vitamin D-related genes (CYP24A1, TGFB1, IGFBP2, IGFBP3, VGF, AGAP2, DENND6B, LRRC8A, BCL6, FCER2, ELL, CD36, AGPAT1, and TMCO6) were associated with high risk and three (NCOA7, GSR, and MPC1) were identified as protective factors. Researches have demonstrated that dysregulation of vitamin Drelated pathways contributes to the pathogenesis of CRC (Dou et al 2016;Sluyter et al 2021;Vladimirov et al 2020). Studies have demonstrated that some vitamin D-related genes of this signature are involved in metabolism, including AGPAT1, VGF, and MPC1 (Agarwal et al 2017;Stephens et al 2017;You et al 2021).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "Identification of Vitamin D-related gene signature to predict colorectal cancer prognosis (v0.1)"

Rathod¹

2021

0

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most common malignant carcinomas worldwide with poor prognosis, imposing an increasingly heavy burden on patients. Previous experiments and epidemiological studies have shown that vitamin D and vitamin D-related genes play a vital role in CRC. Therefore, we aimed to construct a vitamin D-related gene signature to predict prognosis in CRC. The CRC data from The Cancer Genome Atlas (TCGA) was performed as the training set. A total of 173 vitamin D-related genes in the TCGA CRC dataset were screened, and 17 genes associated with CRC prognosis were identified from them. Then, a vitamin D-related gene signature consisting of those 17 genes was established by univariate and multivariate Cox analyses. Moreover, four external datasets (GSE17536, GSE103479, GSE39582, and GSE17537) were used as testing set to validate the stability of this signature. The high-risk group presented a significantly poorer overall survival than low-risk group in both of training set and testing sets. Besides, the areas under the curve (AUCs) for signature on OS in training set at 1, 3, and 5 years were 0.710, 0.708, 0.710 respectively. The AUCs of the ROC curve in GSE17536 for 1, 3, and 5 years were 0.649, 0.654, and 0.694. These results indicated the vitamin D-related gene signature model could effectively predict the survival status of CRC patients. This vitamin D-related gene signature was also correlated with TNM stage in CRC clinical parameters, and the higher risk score from this model was companied with higher clinical stage. Furthermore, the high accuracy of this prognostic signature was validated and confirmed by nomogram model. In conclusion, we have proposed a novel vitamin D-related gene model to predict the prognosis of CRC, which will help provide new therapeutic targets and act as potential prognostic biomarkers for CRC.

show abstract

Associations of cholesterol and vitamin D metabolites with the risk for development of high grade colorectal cancer

Cited by 8 publications

References 27 publications

Revealing the Role of High-Density Lipoprotein in Colorectal Cancer

Revealing the Role of High-Density Lipoprotein in Colorectal Cancer

Identification of Vitamin D-related gene signature to predict colorectal cancer prognosis

Peer Review #1 of "Identification of Vitamin D-related gene signature to predict colorectal cancer prognosis (v0.1)"

Contact Info

Product

Resources

About