Current evidence and therapeutic implication of PANoptosis in cancer.

Regulated cell death (RCD) is considered a critical pathway in cancer therapy, contributing to eliminating cancer cells and influencing treatment outcomes. The application of RCD in cancer treatment is marked by its potential in targeted therapy and immunotherapy. As a type of RCD, PANoptosis has emerged as a unique form of programmed cell death (PCD) characterized by features of pyroptosis, apoptosis, and necroptosis but cannot be fully explained by any of these pathways alone. It is regulated by a multi-protein complex called the PANoptosome. As a relatively new concept first described in 2019, PANoptosis has been shown to play a role in many diseases, including cancer, infection, and inflammation. This study reviews the application of PCD in cancer, particularly the emergence and implication of PANoptosis in developing therapeutic strategies for cancer. Studies have shown that the characterization of PANoptosis patterns in cancer can predict survival and response to immunotherapy and chemotherapy, highlighting the potential for PANoptosis to be used as a therapeutic target in cancer treatment. It also plays a role in limiting the spread of cancer cells. PANoptosis allows for the elimination of cancer cells by multiple cell death pathways and has the potential to address various challenges in cancer treatment, including drug resistance and immune evasion. Moreover, active investigation of the mechanisms and potential therapeutic agents that can induce PANoptosis in cancer cells is likely to yield effective cancer treatments and improve patient outcomes. Research on PANoptosis is still ongoing, but it is a rapidly evolving field with the potential to lead to new treatments for various diseases, including cancer.

High RNA-Binding Motif Protein 3 (RBM3) Expression is Independently Associated with Prolonged Overall Survival in Intestinal-Type Gastric Cancer.

BACKGROUND High expression of the RNA-binding motif protein 3 (RBM3) has previously been described as a favorable clinicopathological factor in several cancers, including ovarian cancer, colorectal cancer, prostate cancer, and breast cancer. The aim of this study was to examine the prognostic implications of RBM3 expression in gastric cancer. MATERIAL AND METHODS Immunohistochemical analysis of RBM3 expression from 123 patients showed that upregulated RBM3 was mainly found in intestinal-type (n=78, case=59) cancer compared to diffuse-type (n=15, case=8) and mixed-type (n=30, case=17). There were no significant differences in RBM3 expression in subgroups of clinicopathological parameters. RBM3 expression was strongly associated with p53 but not with Ki-67. Cox univariate analysis revealed that high RBM3 expression was closely associated with prolonged overall survival time (HR 0.504, 95% CI: 0.300-0.845, P=0.009). Multivariate analysis remained supporting these associations when adjusted for age, sex, tumor size, differentiation grade, TNM stage, lymphatic invasion, and Ki-67 and p53 expression (HR 0.541, 95% CI: 0.308-0.952, P=0.033), where Lauren grade was not included. Lauren grade was the only factor with independent prognostic significance in a model adjusted for all factors. These results were confirmed by Kaplan-Meier analysis. RESULTS Therefore, together with the upregulated RBM3 expression observed in intestinal-type of Lauren grade, we suggest that upregulation of RBM3 is partially responsible for the favorable overall survival in cases with intestinal Lauren grade, which is demonstrated by the box diagram and Kaplan-Meier analysis. Our results showed that high RBM3 expression in gastric cancer is mainly found in intestinal-type of Lauren grade and is associated with longer overall survival time. CONCLUSIONS We found that RBM3 is a potential biomarker of good prognosis and deserves further validation.