Abstract
Objective
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.
Materials and Methods
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.
Results
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.
Conclusion
We identify potential drug targets for metastatic penile cancer through next-generation
RNA sequencing.
Keywords
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Article Info
Publication History
Published online: January 06, 2022
Accepted:
January 2,
2022
Received in revised form:
December 21,
2021
Received:
April 16,
2021
Identification
Copyright
Published by Elsevier Inc.
