BRAF V600E mutation is a predictive indicator of upfront chemotherapy for stage�IV colorectal cancer

Abstract

In stage IV colorectal cancer (CRC), initial resection of the primary tumor is considered to be an important strategy for improving disease outcome. However, there is no consensus on the timing as to when the surgical intervention of the primary tumor should occur. The present study hypothesizes that genetic profiles in CRC may indicate the appropriate treatment strategies for patients with stage IV CRC, and a cohort of 113 patients with stage IV CRC resected primary lesions at various periods were analyzed for the presence of mutations in the KRAS, exon 2, and BRAF genes, exon 15, and for the microsatellite instability status of the tumor. These data were additionally correlated with various clinicopathological features. Although BRAF-mutant was revealed to be an independent negative prognostic factor in stage IV CRC (HR, 8.42; 95% confidence interval, 2.72–26.02), BRAF-mutant samples exhibited better prognoses if they were treated with chemotherapy prior to tumor resection. Thus, the presence of BRAF mutations provides a compelling rationale for the establishment of intensive upfront chemotherapy to improve survival in stage IV CRC.

<p>The Role of Dynamic ctDNA Monitoring During Combination Therapies of BRAF V600E-Mutated Metastatic Colorectal Cancer: A Case Report</p>

“…Such mutation defines a specific subgroup of CRC with poor prognosis. 3,4 Current NCCN guideline recommended combination treatment of…”

SIRT1 Expression and BRAF V600E Mutation in Papillary Thyroid Cancer: Implications for Diagnosis and Prognosis

“…In melanoma, patients with BRAF V600E mutations have a poor prognosis (27). Thus, BRAF V600E has been used as a molecular marker with diagnostic, prognostic, and predictive values for a variety of tumors (15,33,34). As the most common mutation in PTC, BRAF V600E mutations are associated with large tumor lesions, multiple lesions, extraglandular infiltration, and lymph node metastasis, indicating that BRAF mutations are closely associated with poor prognosis of PTC (35,36).…”

Upregulation of microRNA‑31 is associated with poor prognosis in patients with advanced colorectal cancer

“…The present study investigated miR-31 that is significantly associated with advanced CRC with BRAF V600E mutation, as the presence of BRAF mutations is known to be a poor prognostic factor in CRC (14)(15)(16)(17)(18). According to the results of the microarray analysis, it was revealed that miR-31 expression is upregulated in BRAF-mutant tumors.…”

“…microRNAs (miRNA/miR) have been revealed as candidates in tumor progression in various cancer types, and changes in their expression levels are consequently being investigated with the purpose of identifying clinical biomarkers (3)(4)(5)(6)(7)(8)(9). miRNAs constitute a class of small, non-coding RNA molecules, [18][19][20][21][22][23][24][25][26][27] nucleotides in length that function as post-transcriptional regulators of gene expression, either serving as oncogenes or tumor suppressor genes (10,11). In CRC, several miRNAs are aberrantly expressed and target genes downstream of epidermal growth factor receptor (EGFR) signaling; for example, miR-143 and -145 target KRAS and BRAF proteins, respectively (12).…”