TY - JOUR
T1 - Transcriptomic, Proteomic, and Genomic Mutational Fraction Differences Based on HPV Status Observed in Patient-Derived Xenograft Models of Penile Squamous Cell Carcinoma
AU - Zacharias, Niki M.
AU - Segarra, Luis
AU - Akagi, Keiko
AU - Fowlkes, Natalie Wall
AU - Chen, Huiqin
AU - Alaniz, Angelita
AU - de la Cerda, Carolyn
AU - Pesquera, Pedro
AU - Xi, Yuanxin
AU - Wang, Jing
AU - Chahoud, Jad
AU - Lu, Xin
AU - Rao, Priya
AU - Martinez-Ferrer, Magaly
AU - Pettaway, Curtis A.
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/3
Y1 - 2024/3
N2 - Metastatic penile squamous cell carcinoma (PSCC) has only a 50% response rate to first-line combination chemotherapies and there are currently no targeted-therapy approaches. Therefore, we have an urgent need in advanced-PSCC treatment to find novel therapies. Approximately half of all PSCC cases are positive for high-risk human papillomavirus (HR-HPV). Our objective was to generate HPV-positive (HPV+) and HPV-negative (HPV−) patient-derived xenograft (PDX) models and to determine the biological differences between HPV+ and HPV− disease. We generated four HPV+ and three HPV− PSCC PDX animal models by directly implanting resected patient tumor tissue into immunocompromised mice. PDX tumor tissue was found to be similar to patient tumor tissue (donor tissue) by histology and short tandem repeat fingerprinting. DNA mutations were mostly preserved in PDX tissues and similar APOBEC (apolipoprotein B mRNA editing catalytic polypeptide) mutational fractions in donor tissue and PDX tissues were noted. A higher APOBEC mutational fraction was found in HPV+ versus HPV− PDX tissues (p = 0.044), and significant transcriptomic and proteomic expression differences based on HPV status included p16 (CDKN2A), RRM2, and CDC25C. These models will allow for the direct testing of targeted therapies in PSCC and determine their response in correlation to HPV status.
AB - Metastatic penile squamous cell carcinoma (PSCC) has only a 50% response rate to first-line combination chemotherapies and there are currently no targeted-therapy approaches. Therefore, we have an urgent need in advanced-PSCC treatment to find novel therapies. Approximately half of all PSCC cases are positive for high-risk human papillomavirus (HR-HPV). Our objective was to generate HPV-positive (HPV+) and HPV-negative (HPV−) patient-derived xenograft (PDX) models and to determine the biological differences between HPV+ and HPV− disease. We generated four HPV+ and three HPV− PSCC PDX animal models by directly implanting resected patient tumor tissue into immunocompromised mice. PDX tumor tissue was found to be similar to patient tumor tissue (donor tissue) by histology and short tandem repeat fingerprinting. DNA mutations were mostly preserved in PDX tissues and similar APOBEC (apolipoprotein B mRNA editing catalytic polypeptide) mutational fractions in donor tissue and PDX tissues were noted. A higher APOBEC mutational fraction was found in HPV+ versus HPV− PDX tissues (p = 0.044), and significant transcriptomic and proteomic expression differences based on HPV status included p16 (CDKN2A), RRM2, and CDC25C. These models will allow for the direct testing of targeted therapies in PSCC and determine their response in correlation to HPV status.
KW - APOBEC mutations
KW - human papillomavirus-positive penile squamous cell carcinoma
KW - patient-derived xenograft
KW - penile squamous cell carcinoma
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U2 - 10.3390/cancers16051066
DO - 10.3390/cancers16051066
M3 - Article
C2 - 38473423
AN - SCOPUS:85187884646
SN - 2072-6694
VL - 16
JO - Cancers
JF - Cancers
IS - 5
M1 - 1066
ER -