Prognostic Value of <i>LINC-ROR</i> (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 (<i>LINC-ROR</i>) is aberrantly expressed in several types of cancer, including colon cancer (CC). <i>LINC-ROR</i> intronic variant rs1942347 may impact gene regulation and disease p...
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MDPI AG
2022-04-01
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| author | Aly A. M. Shaalan Sara H. Mokhtar Hanadi Talal Ahmedah Amany I. Almars Eman A. Toraih Afaf T. Ibrahiem Manal S. Fawzy Mai A. Salem |
| author_facet | Aly A. M. Shaalan Sara H. Mokhtar Hanadi Talal Ahmedah Amany I. Almars Eman A. Toraih Afaf T. Ibrahiem Manal S. Fawzy Mai A. Salem |
| author_sort | Aly A. M. Shaalan |
| collection | DOAJ |
| description | Emerging studies show that long intergenic non-protein coding RNA, regulator of reprogramming (<i>LINC-ROR</i>) is aberrantly expressed in several types of cancer, including colon cancer (CC). <i>LINC-ROR</i> intronic variant rs1942347 may impact gene regulation and disease phenotype. We aimed to explore the potential association of <i>LINC-ROR</i> (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, <i>p</i> = 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, <i>p</i> = 0.003), homozygote (OR = 5.0, 95%CI = 1.69–14.29, <i>p</i> = 0.003), dominant (OR = 3.33, 95%CI = 1.20–9.09, <i>p</i> = 0.003), and recessive (OR = 2.63, 95%CI = 1.37–5.0, <i>p</i> = 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 <i>LINC-ROR</i> (rs1942347) variant with CC prognosis. |
| first_indexed | 2024-03-09T11:06:32Z |
| format | Article |
| id | doaj.art-d38ee3a2d5af459b9f7a2c12db469299 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-09T11:06:32Z |
| publishDate | 2022-04-01 |
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| spelling | doaj.art-d38ee3a2d5af459b9f7a2c12db4692992023-12-01T00:57:01ZengMDPI AGBiomolecules2218-273X2022-04-0112456910.3390/biom12040569Prognostic Value of <i>LINC-ROR</i> (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched AnalysisAly A. M. Shaalan0Sara H. Mokhtar1Hanadi Talal Ahmedah2Amany I. Almars3Eman A. Toraih4Afaf T. Ibrahiem5Manal S. Fawzy6Mai A. Salem7Department of Anatomy, Faculty of Medicine, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Rabigh 21911, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Surgery, Division of Endocrine and Oncologic Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USADepartment of Pathology, Faculty of Medicine, Northern Border University, Arar 1321, Saudi ArabiaDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, EgyptDepartment of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptEmerging studies show that long intergenic non-protein coding RNA, regulator of reprogramming (<i>LINC-ROR</i>) is aberrantly expressed in several types of cancer, including colon cancer (CC). <i>LINC-ROR</i> intronic variant rs1942347 may impact gene regulation and disease phenotype. We aimed to explore the potential association of <i>LINC-ROR</i> (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, <i>p</i> = 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, <i>p</i> = 0.003), homozygote (OR = 5.0, 95%CI = 1.69–14.29, <i>p</i> = 0.003), dominant (OR = 3.33, 95%CI = 1.20–9.09, <i>p</i> = 0.003), and recessive (OR = 2.63, 95%CI = 1.37–5.0, <i>p</i> = 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 <i>LINC-ROR</i> (rs1942347) variant with CC prognosis.https://www.mdpi.com/2218-273X/12/4/569colon cancerLINC-RORrs1942347single nucleotide polymorphismprognosis |
| spellingShingle | Aly A. M. Shaalan Sara H. Mokhtar Hanadi Talal Ahmedah Amany I. Almars Eman A. Toraih Afaf T. Ibrahiem Manal S. Fawzy Mai A. Salem Prognostic Value of <i>LINC-ROR</i> (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis Biomolecules colon cancer LINC-ROR rs1942347 single nucleotide polymorphism prognosis |
| title | Prognostic Value of <i>LINC-ROR</i> (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis |
| title_full | Prognostic Value of <i>LINC-ROR</i> (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis |
| title_fullStr | Prognostic Value of <i>LINC-ROR</i> (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis |
| title_full_unstemmed | Prognostic Value of <i>LINC-ROR</i> (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis |
| title_short | Prognostic Value of <i>LINC-ROR</i> (rs1942347) Variant in Patients with Colon Cancer Harboring BRAF Mutation: A Propensity Score-Matched Analysis |
| title_sort | prognostic value of i linc ror i rs1942347 variant in patients with colon cancer harboring braf mutation a propensity score matched analysis |
| topic | colon cancer LINC-ROR rs1942347 single nucleotide polymorphism prognosis |
| url | https://www.mdpi.com/2218-273X/12/4/569 |
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