Keller Brian A, Palidwor Gareth, Pastukhova Elena, Gorski Zuzanna, Schieda Nicola, Hogan Kevin, Borowy-Borowski Paul, Sekhon Harman, Flood Trevor A
London Health Sciences Centre, Western University, London, ON, Canada.
Ottawa Hospital Research Institute, Bioinformatics Core Facility, Ottawa, Canada.
Virchows Arch. 2025 Jul 9. doi: 10.1007/s00428-025-04166-7.
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.
阴茎鳞状细胞癌（PSCC）分为人乳头瘤病毒（HPV）相关亚型和HPV非相关亚型。侵袭性和转移性PSCC由于有效的全身治疗选择有限，带来了重大的治疗挑战。多胺是参与细胞增殖和肿瘤进展的重要细胞内调节剂，鸟氨酸脱羧酶1（ODC1）是多胺代谢中的限速酶。我们对21例PSCC肿瘤进行了RNA测序，以研究ODC1的表达。在21例肿瘤中有10例（47.6%）检测到ODC1过表达，与HPV相关肿瘤（3/9，33.3%）相比，在HPV非相关病例中更为常见（7/12，58.3%）。免疫组织化学证实21例肿瘤中有5例（23.8%）ODC1呈阳性，所有这些肿瘤均过表达ODC1且为HPV非相关型。重要的是，ODC1过表达和免疫染色阳性与总体生存率显著降低相关（p<0.05）。这些结果表明，ODC1过表达和免疫染色阳性与PSCC的不良预后相关，支持ODC1作为预后生物标志物的价值，并鉴于现有针对ODC1活性的抗癌药物，突出了其作为新型治疗靶点的潜力。
