Prognostic value of BRAF/MIR-17 signature and B-Raf protein expression in patients with colorectal cancer: A pilot study

被引:10
|
作者
Ibrahiem, Afaf T. [1 ,2 ]
Fawzy, Manal S. [3 ,4 ]
Abu AlSel, Baraah T. [5 ]
Toraih, Eman A. [6 ,7 ]
机构
[1] Northern Border Univ, Fac Med, Dept Pathol, Ar Ar, Saudi Arabia
[2] Mansoura Univ, Fac Med, Dept Pathol, Mansoura, Egypt
[3] Northern Border Univ, Fac Med, Dept Biochem, Ar Ar, Saudi Arabia
[4] Suez Canal Univ, Fac Med, Dept Med Biochem & Mol Biol, Ismailia, Egypt
[5] Northern Border Univ, Fac Med, Dept Microbiol, Ar Ar, Saudi Arabia
[6] Tulane Univ, Sch Med, Dept Surg, New Orleans, LA 70112 USA
[7] Suez Canal Univ, Fac Med, Histol & Cell Biol Dept, Genet Unit, Ismailia, Egypt
关键词
BRAF; colorectal cancer; gene expression; IHC; miR‐ 17; prognosis; qPCR; BRAF V600E; MIR-17-92; CLUSTER; MISMATCH-REPAIR; TRANSITION; MICRORNAS; DIAGNOSIS; PATHWAY; MARKERS; PCR;
D O I
10.1002/jcla.23679
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Background Despite the recent improvement in colorectal cancer (CRC) treatment, it still has a poor prognosis with a low survival rate. Genetic and epigenetic mechanisms have proved to play a substantial role in CRC tumorigenesis and progression. According to Gene Ontology and TargetScan analyses, the B-Raf proto-oncogene (BRAF) gene is one of the microRNA-17 (miR-17) targets. We aimed to explore the prognostic value of B-Raf protein and BRAF/microRNA-17 (MIR-17) gene expression signature in CRC archived samples. Methods B-Raf protein expression was identified by immunohistochemistry, while gene expression studies were quantified by real-time qPCR in 53 paired archived CRC specimens. Results The BRAF showed higher expressions in CRC specimens relative to non-cancer tissues (p = 0.006). MIR17 expression was inversely and significantly correlated with both B-Raf protein (r = -0.79, p < 0.001) and gene expression (r = -0.35, p = 0.010) and showed a significant direct correlation with a high rate of relapse (p = 0.020). BRAF/miR-17 expression in CRC was associated inversely with tumor size, high grade of colonic carcinoma, lymph node metastasis, and carcinoma subtype. Spearman correlation and Kaplan-Meier survival curve analyses revealed that disease-free survival and overall survival were inversely and significantly correlated with positive B-Raf protein expression (r = -0.31 and -0.35, p = 0.023 and 0.011, respectively) and directly correlated with log BRAF/MIR17 ratio (r = 0.50 and 0.41, p < 0.001 and = 0.003, respectively). Cox hazard regression analysis revealed the BRAF/MIR17 ratio could predict both types of patients' survival, among other variables. Conclusion BRAF/MIR17 ratio could have prognostic utility in patients with CRC. Further larger-scale studies are warranted to confirm this utility.
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页数:12
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