Gene Expression Profiling of Advanced Penile Squamous Cell Carcinoma Receiving Cisplatin-based Chemotherapy Improves Prognostication and Identifies Potential Therapeutic Targets

Andrea Necchi, Bernhard J. Eigl, Eddy Shih Hsin Yang, Sejong Bae, Darshan Chandrashekar, Dongquan Chen, Gurudatta Naik, Amitkumar Mehta, Patrizia Giannatempo, Maurizio Colecchia, Jennifer Gordetsky, Shi Wei, Tiffiny Cooper, Sooryanarayana Varambally, Guru Sonpavde

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

In men with advanced penile squamous cell carcinoma receiving first-line chemotherapy, visceral metastases (VM) and Eastern Cooperative Oncology Group performance status ≥1 are poor prognostic factors for overall survival (OS). We hypothesized that tumor gene expression profiling may enhance prognostic stratification and identify potential therapeutic targets. In this retrospective study, RNA extracted from macrodissected tumors underwent profiling for the expression of 738 genes using NanoString. Univariate and multivariate analyses assessed the association of genes, VM, and performance status with OS. Tumors were available from 25 men who received first-line cisplatin-based chemotherapy. In univariate analysis, upregulated MAML2 (p = 0.004), KITLG (p ≤ 0.0001), and JAK1 (p = 0.029) genes were associated with poor OS, and upregulated FANCA was associated with better OS (p = 0.024). In stepwise multivariate analyses, VM (hazard ratio = 12.75, p = 0.0001) and MAML2 (hazard ratio = 10.411, p = 0.003) were associated with poor OS. The presence of none, one, and both of these poor risk factors was associated with significantly different median OS of 18.4 mo, 7.2 mo, and 2.1 mo, respectively. Unsupervised clustering demonstrated two major molecular subtypes with trend for different survivals (p = 0.052). Validation of results is necessary. Patient summary: The expression of the MAML2 gene in penile cancers from men receiving first-line cisplatin-based chemotherapy predicted overall survival independent of clinical factors. In men with advanced penile squamous cell carcinoma receiving first-line cisplatin-based chemotherapy, visceral metastases and tumor tissue MAML2 gene expression were independently associated with poor overall survival. KITLG, JAK1, and MAML2 may also warrant evaluation as therapeutic targets.

Original languageEnglish
Pages (from-to)733-736
Number of pages4
JournalEuropean Urology Focus
Volume4
Issue number5
DOIs
StatePublished - Sep 2018

Bibliographical note

Publisher Copyright:
© 2016 European Association of Urology

Keywords

  • Advanced
  • Cisplatin
  • Gene expression
  • Penile squamous cell carcinoma
  • Prognosis

ASJC Scopus subject areas

  • Urology

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