RNA-seq of penile squamous cell carcinoma shows ODC1 overexpression is associated with worse overall survival.

Penile squamous cell carcinoma (PSCC) is classified into human papillomavirus (HPV)-associated and HPV-independent subtypes. Aggressive and metastatic PSCCs pose significant treatment challenges due to limited effective systemic options. Polyamines are essential intracellular regulators involved in cell proliferation and tumor progression, with ODC1 serving as the rate-limiting enzyme in polyamine metabolism. We used RNA sequencing on 21 PSCC tumors to investigate ODC1 expression. ODC1 overexpression was identified in 10/21 (47.6%) tumors with a higher prevalence in HPV-independent cases (7/12, 58.3%) compared to HPV-associated tumors (3/9, 33.3%). Immunohistochemistry confirmed ODC1 positivity in 5/21 (23.8%) tumors, all of which overexpressed ODC1 and were HPV-independent. Importantly, ODC1 overexpression and positive immunostaining correlated with significantly worse overall survival (p < 0.05). These results indicate that ODC1 overexpression and positive immunostaining are associated with poor prognosis in PSCC, supporting ODC1's value as a prognostic biomarker and highlighting its potential as a novel therapeutic target, given available anti-cancer drugs targeting ODC1 activity.