Chemoresistance in distant micrometastatic lesions may account for diminished durable response rates in advanced penile cancer. However, there are limited studies on new therapeutic targets and the identification of biomarkers that predict chemotherapy response in this population.
Thus, we examine the expression of candidate biomarkers of cisplatin resistance, ERCC1 and E2F1, and perform next-generation sequencing on the cancer transcriptome in a penile cancer cohort.
In this retrospective cohort study, we identified 71 patients treated for penile squamous cell carcinoma between 2009 and 2019. Immunohistochemistry staining for ERCC1 and E2F1 was performed. H-scores were measured for patient specimens obtained from adjacent normal skin, primary tumor and metastatic lymph node specimens and correlated with RNA expression data obtained through next-generation sequencing.
Of the 71 patients identified, 51 and 8 had available surgical specimens for immunohistochemistry and RNA sequencing, respectively. Median H-scores for ERCC1 in adjacent normal skin, primary and metastatic tumors were 17.04, 3.15, and 7.9 respectively compared to E2F1 (43.95, 15.54, 7.9). The median H-score for E2F1 was higher in poorly differentiated primary tumors (24.86) compared to well (7.62) and moderately differentiated (9.55, p = 0.055). Next generation sequencing showed no difference in RNA expression of E2F1 nor ERCC1 between primary tumors and metastatic lesions however did demonstrate elevated RNA expression of genes such as MMP1, and MMP10 in primary tumors compared to adjacent normal skin.
We identify potential drug targets for metastatic penile cancer through next-generation RNA sequencing.
Clinical genitourinary cancer. 2022 Jan 06 [Epub ahead of print]
Christine Ibilibor, Amanda L Watson, Hanzhang Wang, Gabriela Gonzalez, Sitai Liang, David Alonzo, Ronald Rodriguez
Department of Urology, University of Virginia, Charlottesville, VA. Electronic address: ., Department of Urology, University of Texas Health at San Antonio, San Antonio, TX., Department of Pathology and Laboratory Medicine, University of Texas Health at San Antonio, San Antonio, TX., Department of Urology, Doctor's Hospital Renaissance, Edinberg, TX.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35067474