Prognostic implications of TOR1B expression across cancer types: a focus on basal-like breast cancer and cellular adaptations to hypoxia

Abstract

AbstractThe TOR1B gene is known to play a pivotal role in maintaining cellular homeostasis and responding to endoplasmic reticulum stress. However, its involvement in cancer remains relatively understudied. This study seeks to explore the prognostic implications of TOR1B across various cancers, with a specific focus on Basal-like Breast Cancer (BLBC) and its underlying cellular mechanisms. Through comprehensive analysis of data from TCGA, TARGET, GEO, and GTEx, we investigated TOR1B expression and its correlation with patient outcomes. Furthermore, in vitro experiments conducted on BLBC cell lines examined the impact of TOR1B modulation on cell viability, apoptosis, and metabolic activity under varying oxygen levels. Our statistical analysis encompassed differential expression analysis, survival analysis, and multivariate Cox regression. Our findings indicate that TOR1B is overexpressed in BLBC and other cancers, consistently correlating with poorer prognosis. Elevated TOR1B levels were significantly associated with reduced overall and disease-free survival in BLBC patients. In vitro experiments further revealed that TOR1B knockdown augmented apoptosis and influenced metabolic activity, particularly under hypoxic conditions, highlighting its potential role in cancer cell adaptation to stress. Overall, our study underscores the importance of TOR1B in cancer progression, particularly in BLBC, where it serves as a notable prognostic indicator. The interaction between TOR1B and metabolic pathways, as well as its regulation by HIF-1α, suggests its significance in adapting to hypoxia, thereby positioning TOR1B as a promising therapeutic target for aggressive breast cancer subtypes.