The Prognostic Significance of Anisomycin-Activated Phospho-c-Jun NH2-Terminal Kinase (p-JNK) in Predicting Breast Cancer Patients’ Survival Time

Abstract

This study aims to investigate the prognostic significance of p-JNK in breast cancer patients receiving neoadjuvant chemotherapy (NACT) and analyze the relationship between anisomycin, p-JNK. A total of 104 breast cancer patients had NACT were enrolled in this study. The western blot and immunohistochemistry assays were used to determine the protein expressions of p-JNK in human breast cancer cell lines and patients’ cancer tissues. The chi-square test and Fisher’s exact test were adopted to gauge the associations between breast cancer and clinicopathological variables by p-JNK expression, whereas the univariate and multivariate Cox proportional hazards regression models were used to analyze the prognostic value of p-JNK expression. The Kaplan-Meier plots and the log-rank test were adopted to determine patients’ disease-free survival (DFS) and overall survival (OS). Findings indicated that the p-JNK expression had prognostic significance in univariate and multivariate Cox regression survival analyses. Results of log-rank methods showed that: (1) the mean DFS and OS times in patients with high p-JNK expression were significantly longer than those in patients with low p-JNK expression (χ2 = 5.908, P = 0.015 and χ2 = 6.593, P = 0.010, respectively). p-JNK expression is a significant prognostic factor that can effectively predict the survival in breast cancer patients receiving NACT. Treatment with the JNK agonist anisomycin can induce apoptosis, lead to increased p-JNK expression and decreased p-STAT3 expression. Moreover, the p-JNK expression was inversely correlated with p-STAT3 expression.

A Novel Risk Model Based on Lipid Metabolism-Associated Genes Predicts Prognosis and Indicates Immune Microenvironment in Breast Cancer

“…All the genes in our constructed risk model were related to tumors prognosis. Risk models are an applicable method for developing prognostic molecular biomarkers and have been constructed for a variety of tumors, showing powerful predictive ability ( Chen et al, 2021 ; Lv et al, 2021 ). Generally, the patients were scored according to candidate-gene expression values and coefficients, and lower scores indicated a favorable prognosis.…”

PD-L1 Protein Expression Is Associated With Good Clinical Outcomes and Nomogram for Prediction of Disease Free Survival and Overall Survival in Breast Cancer Patients Received Neoadjuvant Chemotherapy

“…The breast cancer tissues and adjacent normal breast tissues were fixed in methanol, embedded in paraffin, sectioned, and performed immunohistochemical analyses. According to the instructions of the manufacturer, the immunohistochemical staining was performed using a two-step kit, details of which have been described in our previously study ( 24 ). The PD-L1 levels were detected using the primary monoclonal antibody directed against PD-L1 (GB14132, dilution 1:500, Servicebio, China).…”

Phosphorylation of Bcl‐2 by JNK confers gemcitabine resistance in lung cancer cells by reducing autophagy‐mediated cell death

“…Furthermore, the results in Figure 4B indicate that the concomitant addition of a JNK inhibitor (SP600125) to parental CL1‐0 cells during GEM treatment significantly reduced the GEM‐induced expression of p‐Bcl‐2 and autophagy‐related proteins 46–48 . Conversely, GEM‐induced p‐Bcl‐2 and autophagy‐related protein expression were significantly enhanced after adding the JNK activator (anisomycin) to GEM‐R CL1‐0 cells 47,49,50 . To further prove that changes in JNK activity can affect the GEM‐induced dissociation of Bcl‐2 and Beclin‐1 in parental and GEM‐R CL1‐0 cells, the immunoprecipitation results in Figure 4C show that the addition of SP600125 to parental CL1‐0 cells significantly reduced GEM‐induced dissociation of Bcl‐2 and Beclin‐1.…”

“…[46][47][48] Conversely, GEM-induced p-Bcl-2 and autophagy-related protein expression were significantly enhanced after adding the JNK activator (anisomycin) to GEM-R CL1-0 cells. 47,49,50 To further prove that changes in JNK activity can affect the GEM-induced dissociation of Bcl-2 and Beclin-1 in parental and GEM-R CL1-0 cells, the immunoprecipitation results in Figure 4C show that the addition of SP600125 to parental CL1-0 cells significantly reduced GEM-induced dissociation of Bcl-2 and Beclin-1. In contrast, the concomitant addition of anisomycin significantly enhanced the GEM-induced dissociation of Bcl-2 and Beclin-1 in GEM-R CL1-0 cells.…”