No abstract

These results suggest that the functional disconnection in MTL subsystem of the DMN may have association with attention function of BC after chemotherapy.

Neutrophils are significant compositions of solid tumors and exert distinct functions in different types of tumors. However, the precise role of neutrophils in the progression of breast cancer (BC) is presently unclear. In this study, by investigating the single-cell RNA sequencing data, we identify a new neutrophil subset, C5aR1-positive neutrophils, that correlates with tumor progression and poor survival for BC patients. Furthermore, it is discovered that C5aR1-positive neutrophils enhance BC cell glycolysis via upregulating ENO1 expression. Mechanically, C5aR1-positive neutrophil-secreted IL1β and TNFα cooperatively activate ERK1/2 signaling, which phosphorylates WTAP at serine341 and thereby stabilizes WTAP protein. The stabilization of WTAP further promotes RNA m6A methylation of ENO1, impacting the glycolytic activity of BC cells. Importantly, C5aR1-positive neutrophils also promote breast cancer growth in vivo, and this effect is abolished by WTAP silencing. In clinical BC samples, increased C5aR1-positive neutrophils correlate with elevated IL1β, TNFα, and ENO1 expression. A high co-expression of C5aR1-positive neutrophil gene signature and ENO1 predicts worse prognosis of BC patients compared with a low co-expression. Collectively, our study reveals a novel subset of C5aR1-positive neutrophils that induces breast cancer glycolysis via increasing ERK1/2-WTAP-dependent m6A methylation of ENO1. These findings support the potential for exploration of C5aR1-positive neutrophils as a therapeutic target in breast cancer.

The aim of this study is to investigate chemotherapy-induced alterations in the functional framework of the brain, and probe the relationship between these changes and executive function impairments in breast cancer patients. Thirty-three breast cancer patients (BC) after receiving chemotherapy and 31 matched healthy controls (HC) were enrolled in this study. All participants received resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) and neuropsychological background tests. The lower functional connectivity of the posterior cingulate cortex (PCC) was found in the left postcentral gyrus, left precentral gyrus, right superior temporal gyrus, right cingulate gyrus and right middle frontal gyrus. A significant negative correlation was found between the response time on the Trail Making Tests and the functional connectivity strength between the PCC and right middle frontal and right cingulate gyri in breast cancer patients. In addition, the strength of the functional connectivity between the PCC and right middle frontal gyrus had a negative correlation with the response times on the Stroop Interference Test in breast cancer patients. This study demonstrated that BC patients after receiving chemotherapy have abnormal functional connectivity. These findings suggest that functional connectivity changes might play an important role in chemotherapy-induced executive function impairments in breast cancer patients.

These findings suggest that breast cancer patients after chemotherapy demonstrate executive control impairment, and provide evidence that the observed defects are correlated with alternations in the executive network of the brain.