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Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis

Emerging studies show that long intergenic non-protein coding RNA, regulator of reprogramming (LINC-ROR) is aberrantly expressed in several types of cancer, including colon cancer (CC). LINC-ROR intronic variant rs1942347 may impact gene regulation and disease phenotype. We aimed to explore the pote...

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Autores principales: Shaalan, Aly A. M., Mokhtar, Sara H., Ahmedah, Hanadi Talal, Almars, Amany I., Toraih, Eman A., Ibrahiem, Afaf T., Fawzy, Manal S., Salem, Mai A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028515/
https://www.ncbi.nlm.nih.gov/pubmed/35454158
http://dx.doi.org/10.3390/biom12040569
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author Shaalan, Aly A. M.
Mokhtar, Sara H.
Ahmedah, Hanadi Talal
Almars, Amany I.
Toraih, Eman A.
Ibrahiem, Afaf T.
Fawzy, Manal S.
Salem, Mai A.
author_facet Shaalan, Aly A. M.
Mokhtar, Sara H.
Ahmedah, Hanadi Talal
Almars, Amany I.
Toraih, Eman A.
Ibrahiem, Afaf T.
Fawzy, Manal S.
Salem, Mai A.
author_sort Shaalan, Aly A. M.
collection PubMed
description Emerging studies show that long intergenic non-protein coding RNA, regulator of reprogramming (LINC-ROR) is aberrantly expressed in several types of cancer, including colon cancer (CC). LINC-ROR intronic variant rs1942347 may impact gene regulation and disease phenotype. We aimed to explore the potential association of LINC-ROR (rs1942347) with the clinicopathological features and outcome of CC cases. Archived FFPE (n = 180) CC samples were enrolled. Taq-Man allelic discrimination PCR was used for genotyping in propensity-matched cohorts with/without positive staining for mutant BRAF protein after eliminating confounders bias. The rs1942347*A allele variant was associated with high pathological grade, larger tumor size, distant metastasis, and mortality. Multiple logistic regression analysis adjusted by sex and BRAF mutation showed A/A genotype carriers to have 3 times more risk of early onset of cancer (OR = 3.13, 95%CI = 1.28–7.69, p = 0.034) than T/T genotype carriers. Overall analysis showed that rs1942347*A allele carriers had higher risk of mortality under heterozygote (OR = 2.13, 95%CI = 1.08–4.35, p = 0.003), homozygote (OR = 5.0, 95%CI = 1.69–14.29, p = 0.003), dominant (OR = 3.33, 95%CI = 1.20–9.09, p = 0.003), and recessive (OR = 2.63, 95%CI = 1.37–5.0, p = 0.011) models compared to T/T allele carriers. Stratified analysis by BRAF status revealed that the ancestor T/T allele conferred protection in BRAF mutant CC patients and was associated with a 73–93% reduced risk of mortality under heterozygote/homozygote comparison models. Using Kaplan–Meier curves, carriers of the A/A genotype had shorter survival times than T/T cohorts. The univariate Cox regression model revealed that the A/A genotype was associated with a 3.5 times greater mortality risk than the T/T genotype. However, after adjustment by multiple Cox regression analysis, the risk was insignificant. In conclusion, this is the first study identifying the potential association of the LINC-ROR (rs1942347) variant with CC prognosis.
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spelling pubmed-90285152022-04-23 Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis Shaalan, Aly A. M. Mokhtar, Sara H. Ahmedah, Hanadi Talal Almars, Amany I. Toraih, Eman A. Ibrahiem, Afaf T. Fawzy, Manal S. Salem, Mai A. Biomolecules Article Emerging studies show that long intergenic non-protein coding RNA, regulator of reprogramming (LINC-ROR) is aberrantly expressed in several types of cancer, including colon cancer (CC). LINC-ROR intronic variant rs1942347 may impact gene regulation and disease phenotype. We aimed to explore the potential association of LINC-ROR (rs1942347) with the clinicopathological features and outcome of CC cases. Archived FFPE (n = 180) CC samples were enrolled. Taq-Man allelic discrimination PCR was used for genotyping in propensity-matched cohorts with/without positive staining for mutant BRAF protein after eliminating confounders bias. The rs1942347*A allele variant was associated with high pathological grade, larger tumor size, distant metastasis, and mortality. Multiple logistic regression analysis adjusted by sex and BRAF mutation showed A/A genotype carriers to have 3 times more risk of early onset of cancer (OR = 3.13, 95%CI = 1.28–7.69, p = 0.034) than T/T genotype carriers. Overall analysis showed that rs1942347*A allele carriers had higher risk of mortality under heterozygote (OR = 2.13, 95%CI = 1.08–4.35, p = 0.003), homozygote (OR = 5.0, 95%CI = 1.69–14.29, p = 0.003), dominant (OR = 3.33, 95%CI = 1.20–9.09, p = 0.003), and recessive (OR = 2.63, 95%CI = 1.37–5.0, p = 0.011) models compared to T/T allele carriers. Stratified analysis by BRAF status revealed that the ancestor T/T allele conferred protection in BRAF mutant CC patients and was associated with a 73–93% reduced risk of mortality under heterozygote/homozygote comparison models. Using Kaplan–Meier curves, carriers of the A/A genotype had shorter survival times than T/T cohorts. The univariate Cox regression model revealed that the A/A genotype was associated with a 3.5 times greater mortality risk than the T/T genotype. However, after adjustment by multiple Cox regression analysis, the risk was insignificant. In conclusion, this is the first study identifying the potential association of the LINC-ROR (rs1942347) variant with CC prognosis. MDPI 2022-04-12 /pmc/articles/PMC9028515/ /pubmed/35454158 http://dx.doi.org/10.3390/biom12040569 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shaalan, Aly A. M.
Mokhtar, Sara H.
Ahmedah, Hanadi Talal
Almars, Amany I.
Toraih, Eman A.
Ibrahiem, Afaf T.
Fawzy, Manal S.
Salem, Mai A.
Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis
title Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis
title_full Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis
title_fullStr Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis
title_full_unstemmed Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis
title_short Prognostic Value of LINC-ROR (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis
title_sort prognostic value of linc-ror (rs1942347) variant in patients with colon cancer harboring braf mutation: a propensity score-matched analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9028515/
https://www.ncbi.nlm.nih.gov/pubmed/35454158
http://dx.doi.org/10.3390/biom12040569
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