RIPK4 Is an Immune Regulating-Associated Biomarker for Ovarian Cancer and Possesses Generalization Value in Pan-Cancer

Abstract

Ovarian cancer (OC) is the most lethal gynecologic cancer. Many studies have reported that RIPK4 (receptor interacting serine/threonine kinase 4) displayed a dysregulated level in many types of tumors. However, its expressions and functions in OC were rarely reported. The levels of RIPK4 were detected in OC and nontumor specimens using TCGA and GEO datasets. The prognostic values of RIPK4 in patients were determined using Kaplan-Meier methods and Kaplan-Meier assays. GO assays and KEGG pathway assays were carried out for functional enrichments. CIBERSORT was applied for estimating the fractions of immune cell types. Finally, RIPK4 was validated in pan-cancer. In this study, our group found that RIPK4 exhibited a higher level of RIPK4 in OC specimens than nontumor specimens. Survival studies revealed that patients with high RIPK4 expressions showed a shorter overall survival than those with low RIPK4 expression. Multivariate assays further confirmed that RIPK4 expression was an independent prognostic element for OC. KEGG pathway analysis displayed that the dysregulated genes in specimens with high RIPK4 expressions were enriched in focal adhesion, proteoglycans in cancer, central carbon metabolism in cancer, and insulin secretion. Correlation analyses showed that several TICs were positively correlated with RIPK4 expression. The pan-cancer validation results showed that RIPK4 was associated with survival in five tumors. Overall, our findings suggested RIPK4 as a prognostic marker in OC.

Exploring the prognostic significance of arm-level copy number alterations in triple-negative breast cancer

“…Given that RIPK4 has been shown to play a role in the activation of the NF-κB pathway, and its expression negatively correlates with the predicted presence of T cells in human ovarian cancer [ 22 , 33 ], we reasoned that RIPK4 may be modulating the tumor microenvironment. To comprehensively assess how RIPK4 shapes the immune landscape of TNBC, we performed spectral flow cytometry on our experimental lung metastasis assay using a 19-plex antibody panel.…”

“…Given that RIPK4 has been shown to play a role in the activation of the NF-κB pathway, and its expression negatively correlates with the predicted presence of T cells in human ovarian cancer [22,33], we reasoned that RIPK4 may be modulating the tumor microenvironment.…”

Receptor-interacting protein kinase 2 is associated with tumor immune infiltration, immunotherapy-related biomarkers, and affects gastric cancer cells growth in vivo

“…Receptor-interacting protein kinase (RIPK) family genes have been found to be of significant importance to the innate immune system, as they play a role in modulating the progression of immunerelated diseases and tumors [5][6][7][8][9][10][11]. Dysregulation of the innate immune system can lead to immunodeficiency or autoinflammatory diseases.…”

“…The upregulation of RIPK3 has been shown to increase the production of immunostimulatory cytokines in the tumor microenvironment, leading to a robust cytotoxic anti-tumor immune response 9 . Additionally, RIPK4 has been identified as an immune regulating-associated biomarker in ovarian cancer 11 , 29 , where it plays a role in regulating the growth of squamous cell carcinoma 30 and cell-cell adhesion in epidermal development and homeostasis 31 . All of the aforementioned studies have demonstrated the significant role of RIPKs genes in the regulation of immune-related diseases, such as tumors.…”