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

Abstract

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 noncancer 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.

Differential Effect of Three Macrolide Antibiotics on Cardiac Pathology and Electrophysiology in a Myocardial Infarction Rat Model: Influence on Sodium Nav1.5 Channel Expression

“…For each sample, a reaction mixture (15 μL) contains the extracted RNA (5 μL), 100 mM of each deoxynucleotide triphosphate (0.15 μL), MultiScribe ® reverse transcriptase (50 U/μL), RT buffer (10×) (1.5 μL), RNase inhibitor (20 U/mL), SCN5A TaqMan ® specific primers (3 μL of each), and nuclease-free water (4.16 μL), was incubated in the “T-Professional Basic, Biometra PCR System (Biometra, Göttingen, Germany)” for 30 min at 16 °C, then 30 min at 42 °C, and 5 min at 85 °C, with subsequent holding stage at 4 °C. Non-template and non-reverse transcriptase negative controls were applied in each experiment to ensure the absence of genomic DNA contaminations [ 42 ].…”

Cross‐platform comparison of next‐generation sequencing and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry for detecting KRAS/NRAS/BRAF/PIK3CA mutations in cfDNA from metastatic colorectal cancer patients

“…The effectiveness of targeted drugs is raising the awareness about the importance of molecular typing of tumor 6,9 . Considering the tumor accumulate mutations all the time, the demand of molecular typing is always urgent during cancer management.…”

“…The effectiveness of targeted drugs is raising the awareness about the importance of molecular typing of tumor. 6,9 Considering the tumor accumulate mutations all the time, the demand of molecular typing is always urgent during cancer management. Liquid biopsy, especially ctDNA analysis, meets the real-time examining requirement and attracts the attention of clinicians.…”

“…It has been reported that mutation frequencies of KRAS, NRAS, BRAF and PIK3CA in CRC are 35.7%–45.4%, 3.9%–6.3%, 3.1%–7.1%, and 3.5%–16.1%, respectively 2,6 . Meanwhile, these mutations may suppress the response to targeted treatments for metastatic colorectal cancer (mCRC), like epidermal growth factor receptor (EGFR) targeted monoclonal antibodies (mAbs), cetuximab and panitumumab 7–9 . Therefore, it is critically essential to assess the mutation status of these genes in patients 3 …”

“…2,6 Meanwhile, these mutations may suppress the response to targeted treatments for metastatic colorectal cancer (mCRC), like epidermal growth factor receptor (EGFR) targeted monoclonal antibodies (mAbs), cetuximab and panitumumab. [7][8][9] Therefore, it is critically essential to assess the mutation status of these genes in patients. 3 Tumor tissue is a suitable source for mutation detection in cancer patients.…”