ArticleMolecular medicine (Cambridge, Mass.)2022
Pan-cancer analysis reveals RIPK2 predicts prognosis and promotes immune therapy resistance via triggering cytotoxic T lymphocytes dysfunction.
Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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28 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- A systematic review of the latest progress of drug resistance and clinical application of immunotherapy in renal cell carcinoma in the past five years based on bibliometrics.Human vaccines & immunotherapeutics · 2025Pooled it
- Ripk2 promotes CD8Cell death & disease · 2026Article
- Construction of a human epidermal growth factor receptor 2-related gene risk model for predicting breast cancer prognosis.Oncology letters · 2026Article
- Combined immunoscore and pan-immune inflammation value associated with pathological response and survival outcomes in esophageal squamous cell carcinoma receiving neoadjuvant immunotherapy.International journal of surgery (London, England) · 2026Article
- RIPK2 induces docetaxel resistance in prostate cancer through the NF-κB/P-gp signaling pathway.PloS one · 2026Article
- Identifying and validating SMARCAL1 as a prognostic and immunotherapy predictive biomarker for NSCLC.Discover oncology · 2025Article
- Differential expression profiles of immunoregulatory genes in anaplastic thyroid carcinomas with a coexistent papillary carcinoma component.Virchows Archiv : an international journal of pathology · 2025Article
- Comprehensive analysis of MAGE-A10 in pan-cancer and its validation in gastric cancer.Scientific reports · 2025Article
- Pan-cancer analysis reveals the potential role of DHCR24 in bladder cancer via interactions with HRAS to facilitate cholesterol synthesis.Oncology letters · 2025Article
- Unveiling the key mechanisms of FOLR2+ macrophage-mediated antitumor immunity in breast cancer using integrated single-cell RNA sequencing and bulk RNA sequencing.Breast cancer research : BCR · 2025Article
- Overcoming immunotherapy resistance in gastric cancer: insights into mechanisms and emerging strategies.Cell death & disease · 2025Review
- TSPAN4Frontiers in immunology · 2025Article
- The molecular features of lung cancer stem cells in dedifferentiation process-driven epigenetic alterations.The Journal of biological chemistry · 2024Review
- Review
- Article
- Expression of Truncated Products at the 5'-Terminal Region of RIPK2 and Evolutive Aspects that Support Their Biological Importance.Genome biology and evolution · 2024Article
- Oncogenic and immunological roles of RACGAP1 in pan-cancer and its potential value in nasopharyngeal carcinoma.Apoptosis : an international journal on programmed cell death · 2024Article
- Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population.The application of clinical genetics · 2024Article
- Prediction Model for Therapeutic Responses in Ovarian Cancer Patients using Paclitaxel-resistant Immune-related lncRNAs.Current medicinal chemistry · 2024Article
- Mechanisms and biomarkers of immune-related adverse events in gastric cancer.European journal of medical research · 2023Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundReceptor-interacting protein kinase 2 (RIPK2, also known as RIP2) was reported to be associated with bacterial infections as well as inflammatory responses. However, the role of RIPK2 in prognosis and immunotherapy response is yet to be elucidated in human pan-cancer.
methodsIn this study, we investigated the expression, gene alteration landscape and prognostic value of RIPK2 in 33 cancers through various databases including Ualcan, cBioportal and Gene Expression Profiling Interactive Analysis 2 (GEPIA2). Then, the correlation between RIPK2 and immune infiltration, immune score, stromal score, and ESTIMATE score was investigated in the Cancer Genome Atlas (TCGA) and tumor immune estimation resource (TIMER) databases. Independent cohorts were utilized to explore the role of RIPK2 in tumor immunotherapy response. Furthermore, Gene set enrichment analysis (GSEA) was conducted to explore the mechanisms by which RIPK2 regulates immune therapy resistance. Single-cell RNA-seq datasets were used to analyze the expression level of RIPK2 on different immune cells. Moreover, CellMiner database was used to explore the relationship between RIPK2 expression with drug response.
resultCompared with normal tissue, tumor tissue had a higher expression level of RIPK2 in various cancers. Survival analysis showed that high expression of RIPK2 associated with poor prognosis in numerous cancers. RIPK2 was found to promote a series of immune cell infiltration and B cells, macrophages, and neutrophils were significantly positively correlated with the expression of RIPK2. Moreover, RIPK2 affected immune score, stromal score and ESTIMATE score for a wide range of cancers. In the vast majority of 33 cancers, gene co-expression analysis showed that RIPK2 was positively correlated with the expression of immune checkpoint markers, such as PDCD1 (PD-1), CD274 (PD-L1), CTLA4 and TIGIT. RIPK2 aggravated cytotoxic T lymphocyte (CTL) dysfunction and related to the poor efficacy of immune checkpoint blockade in skin cutaneous melanoma (SKCM) and kidney renal clear cell carcinoma (KIRC). High expression of RIPK2 promoted innate immunotherapy resistance and adaptive immunotherapy resistance through IL-6/JAK/STAT3 signaling, interferon-gamma response, and interferon-alpha response pathway.
conclusionsThese results confirmed that RIPK2 could serve as a prognostic biomarker and promoted immune therapy resistance via triggering cytotoxic T lymphocytes dysfunction.
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