Penile squamous cell carcinoma (PSCC) with a poor prognosis lacks reliable biomarkers for stratifying patients. Fas-associated death domain (FADD) could regulate cell proliferation and has shown promising diagnostic and prognostic significance in multiple cancers. However, researchers have not determined how FADD exerts its effect on PSCC. In this study, we set out to investigate the clinical features of FADD and the prognostic impact of PSCC. Additionally, we also assessed the role of affecting the immune environment in PSCC. Immunohistochemistry was carried out to evaluate the protein expression of FADD. The difference between FADDhigh and FADDlow was explored by RNA sequencing from available cases. The immune environment evaluation of CD4, CD8, and Foxp3 was performed by immunohistochemical. In this study, we found that FADD was overexpressed in 19.6 (39/199) patients, and the overexpression of FADD was associated with phimosis (p=0.007), N stage (p<0.001), clinical stage (p=0.001), and histologic grade (p=0.005). The overexpression of FADD was an independent prognostic factor for both PFS (HR 3.976, 95% CI 2.413-6.553, p<0.001) and OS (HR 4.134, 95% CI 2.358-7.247, p<0.001). In addition, overexpression of FADD was mainly linked to T cell activation and PD-L1 expression combined with PD-L1 checkpoint in cancer. Further validation demonstrated that overexpression of FADD was positively correlated with the infiltration of Foxp3 in PSCC (p=0.0142). It is the first time to show that overexpression of FADD is an adjunct biomarker with poor prognosis in PSCC and could also serve as a tumor immune environment regulator.
Virchows Archiv : an international journal of pathology. 2023 Feb 23 [Epub ahead of print]
Ting Xue, Ru Yan, Zaishang Li, Shengjie Guo, Xiao Xiao, Jietian Jin, Lijuan Jiang, Huali Ma, Chong Wu, Tingyu Liu, Lichao Wei, Longbin Xiong, Fangjian Zhou, Kai Yao, Ranyi Liu, Hui Han
Department of Urology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 510060, China., Department of Urology, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518060, China., Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Department of Radiology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China., Department of General Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, China., Department of Urology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 510060, China. ., Department of Urology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Centre for Cancer Medicine, Guangzhou, 510060, China. .