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Prognostic impact of RITA expression in patients with anal squamous cell carcinoma treated with chemoradiotherapy
Franz Rödel1, Kerstin Steinhäuser2, Nina-Naomi Kreis2
1Department of Radiotherapy and Oncology, Goethe-University, Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK) partner site: Frankfurt/Mainz, Heidelberg, Germany.
Background:
RBP-J interacting and tubulin-associated protein (RITA) has been identified as a negative regulator of the Notch signalling pathway and its deregulation is involved in the pathogenesis of several tumour entities. RITA's impact on the response of anal squamous cell carcinoma (SCC) to anticancer treatment, however, remains elusive.
Materials And Methods:
In our retrospective study immunohistochemical evaluation of RITA was performed on 140 pre-treatment specimens and was correlated with clinical and histopathologic characteristics and clinical endpoints cumulative incidence of local control (LC), distant recurrence (DC), disease-free survival (DFS) and overall survival (OS).
Results:
We observed significant inverse correlations between RITA expression and tumour grading, the levels of HPV-16 virus DNA load, CD8 (+) tumour infiltrating lymphocytes and programmed death protein (PD-1) immunostaining. In univariate analyses, elevated levels of RITA expression were predictive for decreased local control (p = 0.001), decreased distant control (p = 0.040), decreased disease free survival (p = 0.001) and overall survival (p < 0.0001), whereas in multivariate analyses RITA expression remained significant for decreased local control (p = 0.009), disease free survival (p = 0.032) and overall survival (p = 0.012).
Conclusion:
These data indicate that elevated levels of pretreatment RITA expression are correlated with unfavourable clinical outcome in anal carcinoma treated with concomitant chemoradiotherapy.
Insights
High RBP-J interacting and tubulin-associated protein (RITA) expression predicts poor outcomes in anal squamous cell carcinoma (SCC) patients treated with chemoradiotherapy, indicating RITA as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- RBP-J interacting and tubulin-associated protein (RITA) is a negative regulator of the Notch signaling pathway.
- Deregulation of RITA is implicated in various cancers.
- The role of RITA in anal squamous cell carcinoma (SCC) treatment response is unknown.
Purpose of the Study:
- To investigate the impact of RITA expression on treatment outcomes in anal SCC.
- To correlate RITA levels with clinical and histopathological features.
Main Methods:
- Retrospective analysis of 140 pre-treatment anal SCC specimens.
- Immunohistochemical evaluation of RITA expression.
- Correlation with clinical endpoints: local control (LC), distant control (DC), disease-free survival (DFS), and overall survival (OS).
Main Results:
- Elevated RITA expression inversely correlated with tumor grade, HPV-16 DNA load, CD8(+) tumor-infiltrating lymphocytes, and PD-1 staining.
- Univariate analysis showed elevated RITA predicted decreased LC, DC, DFS, and OS.
- Multivariate analysis confirmed RITA as a significant predictor of decreased LC, DFS, and OS.
Conclusions:
- Pre-treatment RITA levels are associated with unfavorable clinical outcomes in anal carcinoma patients.
- Elevated RITA expression indicates a poorer prognosis in patients receiving chemoradiotherapy.
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