CCDC69 (Coiled-Coil Domain Containing 69)

The mIHC analysis showed that compared with normal tissues, the levels of HMGB3 in sarcoma tissues was higher, and the high expression of HMGB3 was related to the increased infiltration of CD4 + and CD8 + T cells. This study reveals the potential of combining CCDC69 and HMGB3 with DRGs as a new biomarker for the clinical diagnosis and a potential immunotherapy targets for sarcoma.

Mechanistically, we found that ATRX mutation may regulate coiled-coil domain-containing protein 69 (CCDC69) expression, leading to functional alterations in mast cells and immune unresponsiveness through the modulation of various immune-related signaling pathways. This machine learning-based prognostic model, centered on seven OncoImmune hub DEGs, along with ATRX gene status, represents promising biomarkers for predicting prognosis, molecular characteristics, and immune features in LMS.

Lastly, we conducted immunohistochemistry staining to validate the aforementioned results. In conclusion, we found four M1 MIRGs that may be helpful for the diagnosis, prognosis, and immunotherapy of Her2-positive breast cancer.

Our findings indicate that CDC20 safeguards the heart against DOX-induced cardiotoxicity by modulating CCDC69 degradation without compromising the antitumor efficacy of DOX.

Importantly, we demonstrated that CCDC69 regulates the stability of the CPC by safeguarding its members from degradation during mitosis. In summary, our findings underscore CCDC69's essential role as a mitotic regulator, which is crucial for maintaining the fidelity of chromosome segregation.

Finally, we confirmed that ADAM8 could promote the proliferation, migration and invasion of ccRCC cells through in vitro experiments, and further found that in in vivo experiments, ADAM8 knockdown could inhibit tumor formation in ccRCC cells, improve the therapeutic effect of anti-PD1, and prolong the survival of mice. Our study highlighted the alleviative role of silencing ADAM8 in ccRCC patients.

Our research revealed the clinical significance of CCDC69 in breast cancer and validated the critical roles of CCDC69 in the tumor immune infiltration and immunotherapy responses.