K-Ras4A Plays a More Significant Role than K-Ras4B in Ductal Carcinoma of Breast

Authors
Mohamad Mahdi Mortazavipour 1
Zeinab Mohamadalizadeh-Hanjani 1
Loabat Geranpayeh 2
Reza Mahdian 3
Shirin Shahbazi 1
1 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, ‎ Tehran, Iran
2 Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
3 Molecular Medicine Department, Pasteur Institute of Iran, Tehran, Iran
10.61186/ibj.3857
Abstract
Background: K-Ras mutations rarely occur in breast cancer. However, studies have supported that K-Ras upregulation is involved in breast cancer pathogenesis. Two main K-Ras transcript variants; K-Ras4A and K-Ras4B, originate from the alternative splicing of exon 4. In this study, we aimed to evaluate variations in the expression of K-Ras4A and K-Ras4B and their role in breast ductal carcinoma.

Methods: Total RNA was extracted from breast tumors, and the NATs obtained via mastectomy. Patients were selected from new cases of breast cancer with no prior history of chemotherapy. Relative mRNA expression was calculated based on a pairwise comparison between the tumors and the NATs following normalization to the internal control gene. Predictive values of the transcript variants were examined by ROC curve analysis.

Results: A statistically significant increase was found in the K-Ras4A and K-Ras4B expression with the mean fold changes of 7.58 (p = 0.01) and 2.47 (p = 0.001), respectively. The K-Ras4A/K-Ras4B ratio was lower in the tumors than that of the normal tissues. ROC curve analysis revealed the potential of K-Ras4A (AUC: 0.769) and K-Ras4B (AUC: 0.688) in breast cancer prediction. There was also a significant association between K-Ras4B expression and HER2 statues (p = 0.04). Furthermore, a significant link was detected between K-Ras4A expression and pathological prognostic stages (p = 0.04).

Conclusion: Our findings revealed that expression levels of K-Ras4A and K-Ras4B is higher in the tumor compared to the normal breast tissues. Increase in K-Ras4A expression was more significant than that of K-Ras4B.
Keywords
Alternative splicing
Breast neoplasms
Gene expression
KRAS protein
Real-Time Polymerase Chain Reaction