Prognostic Significance of , and Genes in Breast Cancer: Implications for Survival and Therapeutic Stratification.

BACKGROUND

Breast cancer remains a leading cause of cancer-related mortality among women, highlighting the urgent need for reliable biomarkers that can aid in prognosis and therapeutic stratification.

OBJECTIVES

This study aimed to evaluate the RNA expression levels of four specific genes-, , , and -in breast cancer tumors compared to adjacent normal tissues, and to assess their prognostic significance in relation to clinical parameters and recurrence-free survival.

MATERIALS AND METHODS

The RNA expression levels of , , , and were examined using SYBR Green real-time PCR. Gene expression data were correlated with clinical parameters, including disease stage, lymph node involvement, and triple-negative status. Survival analysis was conducted to evaluate the prognostic significance of these genes concerning recurrence within five years post-diagnosis, with median expression cutoffs established for each gene and the overall median for the panel. Kaplan-Meier survival analysis was employed to assess the relationship between gene expression and recurrence-free survival, calculating hazard ratios (HR) for each gene and the combined panel. Additionally, the Reactome database was analyzed to identify biological pathways associated with these genes.

RESULTS

All four genes demonstrated significantly higher expression levels in breast cancer samples, correlating with advanced disease stages, lymph node involvement, and triple-negative breast cancer status. expression was notably associated with estrogen receptor (ER) and progesterone receptor (PR) positivity, while expression correlated with ER negativity. Survival analysis revealed that 6 out of 40 patients expired within five years. Kaplan-Meier analysis indicated that higher expression levels of (HR 14.80, p=0.0015), (HR 9.259, p=0.0071), (HR 12.49, p=0.0027), and (HR 7.315, p=0.0158) were significantly associated with reduced recurrence-free survival. The hazard ratio for the combined gene panel was 15.367 (p<0.0001). Reactome analysis revealed that these genes are involved in critical biological pathways, including actin folding by CCT TriC and TP53 regulation of G1 cell cycle arrest.

CONCLUSIONS

Our findings suggest that this four-gene panel holds significant promise as a robust prognostic tool for breast cancer survival. This research paves the way for further investigations into targeted therapies and personalized medicine approaches in the management of breast cancer.