Prognostic Significance of E2F8, LIN28b, MACC1, and CCT3 Genes in Breast Cancer: Implications for Survival and Therapeutic Stratification.

Abstract

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-E2F8, LIN28b, MACC1, and CCT3-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 E2F8, LIN28b, MACC1, and CCT3 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. E2F8 expression was notably associated with estrogen receptor (ER) and progesterone receptor (PR) positivity, while MACC1 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 E2F8 (HR 14.80, p=0.0015), LIN28b (HR 9.259, p=0.0071), MACC1 (HR 12.49, p=0.0027), and CCT3 (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.