MMTV Virus Detection, Survival Analysis, and Prognostic Relevance of Six Tumor Genes in Patients With Breast Cancer.

Abstract

Background/objectives: Breast cancer (BC) remains the most frequently diagnosed malignancy among women worldwide and represents a significant global health burden. The genes associated with tumor suppression (p53, BRCA1, and BRCA2), telomere length maintenance (TERT), DNA damage response (FGFR2), and DNA repair (CHD1) are recognized for their intricate function in tumor genesis and progression. However, the prognostic significance of these genes in BC remains an area of research interest. This study aimed to examine the potential association between the presence of the MMTV and the expression patterns of these six genes with patient prognosis and survival outcomes in BC.

Methods: This study includes 125 formalin-fixed, paraffin-embedded (FFPE) tissue specimens taken from BC patients, in addition to 25 tissue samples of benign breast lesions were incorporated as controls. The mRNA expression levels of six genes, namely p53, BRCA1, BRCA2, TERT, FGFR2, and CHD1, were quantified in FFPE tissue samples using quantitative polymerase chain reaction (qPCR). The correlation between gene expression and prognostic characteristics and the probability of recurrence-free survival (RFS) and overall survival (OS) were assessed.

Results: The results do not indicate an association between MMTV and BC, as the virus was not detected in any of the tissue samples analyzed. We observed a significant differential expression in five of the six studied genes between BC and noncancerous breast tissue, with significant downregulation of BRCA1, BRCA2, CHD1, and TERT, significant upregulation of p53, and unchanged levels of FGFR2. Among BC patients, p53 and BRCA1 expression levels emerged as significant prognostic factors for both RFS (32 vs. 24 months; 34 vs. 26 months) and OS (28.5 vs. 24 months; 31 vs. 28 months), respectively. Kaplan-Meier survival analysis of p53 expression displayed a trend favoring low expression for better survival and showing relatively stable RFS and OS survival curves of p53 until 43 and 54 months of the follow-up period, respectively.

Conclusions: When comparing cancer to noncancer patients, only p53 and BRCA1 expression levels emerged as significant prognostic factors for both RFS and OS in the entire cohort, with p53 displaying a trend favoring low expression for better survival. Although gene expression data provided a prognostic value, future studies should aim at integrating multiomics data and evaluating biomarkers in a broader clinical context to improve the accuracy of prognostic models and guide personalized treatment strategies.