Anticancer research · 2026
Prognostic Relevance of FOS and JUN Family Members and Immune Cell Infiltration for the Survival of Patients With Ovarian Carcinoma.
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Dawood Mona, Ooko Ednah, Efferth Thomas, Boulos Joelle C
Аннотация
BACKGROUND/AIM: Ovarian carcinoma is a difficult-to-treat cancer. It is often resistant to chemotherapy and targeted therapy. The 5-year survival rates of patients with advanced tumors are usually below 40%. Immunotherapy represents an emerging treatment option. We investigated the prognostic significance of the oncogenic transcription factor AP-1, formed by the dimerization of FOS and JUN family members.
PATIENTS AND METHODS: Using the KM Plotter algorithm, Kaplan-Meier statistics were applied to calculate survival times of 373 patients with ovarian carcinoma from The Cancer Genome Atlas (TCGA). Expression of AP-1 dimer components (FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND) was based on RNA sequencing. To estimate immune response, increased or decreased tumor infiltration of immune cells was assessed.
RESULTS: High expression of JUNB alone or in combination with FOSB, FOSL1, or FOSL2 (but not with JUN, JUND, or FOS) significantly correlated with shorter survival. Hierarchical clustering of the survival analyses revealed that JUNB (alone or together with FOSB, FOSL1, or FOSL2), combined with decreased counts of CD8+ cytotoxic T cells, regulatory T cells, or natural killer cells, correlated with shorter survival. Conversely, increased tumor infiltration with type 2 T helper cells or basophilic granulocytes and JUNB-containing AP-1 dimers also correlated with poor overall survival.
CONCLUSION: Specific combinations of AP-1 dimer components were of prognostic value for shorter overall survival and were associated with immune cell infiltration linked to "cold" phenotypes non-responsive to immunotherapy. JUNB-containing AP-1 dimers may promote immune evasion and tumor-progressing immune responses. Our results may help identify high-risk patients and support the evaluation of JUNB-containing AP-1 dimers as prognostic factors for ovarian carcinoma.
PATIENTS AND METHODS: Using the KM Plotter algorithm, Kaplan-Meier statistics were applied to calculate survival times of 373 patients with ovarian carcinoma from The Cancer Genome Atlas (TCGA). Expression of AP-1 dimer components (FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND) was based on RNA sequencing. To estimate immune response, increased or decreased tumor infiltration of immune cells was assessed.
RESULTS: High expression of JUNB alone or in combination with FOSB, FOSL1, or FOSL2 (but not with JUN, JUND, or FOS) significantly correlated with shorter survival. Hierarchical clustering of the survival analyses revealed that JUNB (alone or together with FOSB, FOSL1, or FOSL2), combined with decreased counts of CD8+ cytotoxic T cells, regulatory T cells, or natural killer cells, correlated with shorter survival. Conversely, increased tumor infiltration with type 2 T helper cells or basophilic granulocytes and JUNB-containing AP-1 dimers also correlated with poor overall survival.
CONCLUSION: Specific combinations of AP-1 dimer components were of prognostic value for shorter overall survival and were associated with immune cell infiltration linked to "cold" phenotypes non-responsive to immunotherapy. JUNB-containing AP-1 dimers may promote immune evasion and tumor-progressing immune responses. Our results may help identify high-risk patients and support the evaluation of JUNB-containing AP-1 dimers as prognostic factors for ovarian carcinoma.