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.
Highlights
Ovarian cancer (OC) is a significant cause of death from gynecologic cancer [1]
New research results for OC progression are constantly emerging, advanced-stage diseases do not tend to respond well to cytotoxic chemotherapy and are associated with a poor outcome, which encourage researchers to explore sensitive biomarkers and the potential mechanisms involved in OC progression and metastasis for the improvements of clinical outcome of OC patients [5, 6]
To delve into the possible functions of receptor-interacting protein kinase 4 (RIPK4) in OC progression, we applied GEPIA to analyze its expressions in OC specimens and nontumor specimens
Summary
There are >15,000 patients who died of OC each year in the United States [2]. Many patients with early stages do not display specific symptoms, and effective screening methods are limited in clinical practice, which results in >65% of OC patients with advanced stages (FIGO stage III or IV) were diagnosed [3, 4]. New research results for OC progression are constantly emerging, advanced-stage diseases do not tend to respond well to cytotoxic chemotherapy and are associated with a poor outcome, which encourage researchers to explore sensitive biomarkers and the potential mechanisms involved in OC progression and metastasis for the improvements of clinical outcome of OC patients [5, 6]. As a member of the RIPK family, receptor-interacting protein kinase 4 (RIPK4) was originally identified as a regulator involved in protein kinase C (PKC) via yeast two-hybridbased screen [7].
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