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Association of rs6983267 at 8q24, HULC rs7763881 polymorphisms and serum lncRNAs CCAT2 and HULC with colorectal cancer in Egyptian patients

Shaker, Olfat G., Senousy, Mahmoud A., Elbaz, Eman M.·2017·Scientific Reports

Abstract

The impact of HULC rs7763881 on colorectal cancer (CRC) susceptibility is not yet known. Also, the biological function of the cancer-related rs6983267 remains unclear. We investigated the association of these SNPs with the risk of CRC and adenomatous polyps (AP), their correlation with CCAT2 and HULC expression, and the potential of serum CCAT2 and HULC as biomarkers for CRC. 120 CRC patients, 30 AP patients, and 96 healthy controls were included. Genotyping and serum lncRNAs were assayed by qPCR. Studied SNPs were not associated with AP susceptibility. rs6983267 GG was associated with increased CRC risk, whereas rs7763881 AC was protective. rs7763881 and rs6983267 CT haplotype was protective. Serum CCAT2 and HULC were upregulated in CRC and AP patients versus controls and discriminated these groups by ROC analysis. rs6983267 GG and rs7763881 AA patients demonstrated higher serum CCAT2 and HULC compared with GT/TT and AC, respectively. rs6983267 and serum HULC predicted CRC diagnosis among non-CRC groups (AP + controls) by multivariate analysis. Studied SNPs or serum long noncoding RNAs weren’t correlated with nodal or distant metastasis. In conclusion, rs6983267 and rs7763881 are potential genetic markers of CRC predisposition and correlate with serum CCAT2 and HULC, two novel potential non-invasive diagnostic biomarkers for CRC.

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Figure 1 Serum expression levels of HULC and CCAT2. (A) Fold change of serum HULC and CCAT2 expression in patients with CRC (n = 120) and adenomatous polyps (n = 30) compared with healthy controls (n = 96), (B) Fold change of serum HULC and CCAT2 expression in CRC patients compared with non-CRC patients (healthy controls + adenomatous polyps patients, n = 126), (C) Expression of serum HULC in different HULC SNP rs7763881 genotypes (AA, n = 32, and AC, n = 88), and (D) Expression of serum CCAT2 in different rs6983267 genotypes (GG, n = 46, GT, n = 56, TT, n = 18, GT/TT, n = 74). Data are expressed as mean (95% CI). *means statistical significance (P < 0.05).
Figure 1 Serum expression levels of HULC and CCAT2. (A) Fold change of serum HULC and CCAT2 expression in patients with CRC (n = 120) and adenomatous polyps (n = 30) compared with healthy controls (n = 96), (B) Fold change of serum HULC and CCAT2 expression in CRC patients compared with non-CRC patients (healthy controls + adenomatous polyps patients, n = 126), (C) Expression of serum HULC in different HULC SNP rs7763881 genotypes (AA, n = 32, and AC, n = 88), and (D) Expression of serum CCAT2 in different rs6983267 genotypes (GG, n = 46, GT, n = 56, TT, n = 18, GT/TT, n = 74). Data are expressed as mean (95% CI). *means statistical significance (P < 0.05).CC BY · PubMed Central
Figure 2 Diagnostic performance of serum HULC and CCAT2. ROC curve analysis of serum HULC and CCAT2 to discriminate studied groups, CRC (n = 120), adenomatous polyps (n = 30), healthy controls (n = 96), and non-CRC groups (n = 126).
Figure 2 Diagnostic performance of serum HULC and CCAT2. ROC curve analysis of serum HULC and CCAT2 to discriminate studied groups, CRC (n = 120), adenomatous polyps (n = 30), healthy controls (n = 96), and non-CRC groups (n = 126).CC BY · PubMed Central

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Metadata

Authors
Shaker, O. G., Senousy, M. A., & Elbaz, E. M.
Venue
Scientific Reports
Published
2017-11-24
Volume
7
Issue
1
ISSN
2045-2322
Cited by
72
References
1
Language
en

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