Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer

Stephanie Markovina, Songyan Wang, Lauren E. Henke, Cliff J. Luke, Stephen C. Pak, Todd Dewees, John D. Pfeifer, Julie K. Schwarz, Weijun Liu, Shuai Chen, David Mutch, Xiaowei Wang, Matthew A. Powell, Barry A. Siegel, Farrokh Dehdashti, Gary A. Silverman, Perry W. Grigsby

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background:Pretreatment serum squamous cell carcinoma antigen (SCCA) is a prognostic biomarker in women with cervical cancer. SCCA has not been evaluated as an early indicator of response to chemoradiation therapy (CRT). The molecular role of the two SCCA isoforms, SCCA1 (SERPINB3) and SCCA2 (SERPINB4), in cervical cancer is unknown. We hypothesised that changes in serum SCCA during definitive CRT predicts treatment response, and that SCCA1 mediates radiation resistance.Methods:Patients treated with definitive CRT for cervical squamous carcinoma with serum SCCA measured were included. SCCA immunohistochemistry was performed on tumour biopsies. Post-treatment FDG-PET/CT, recurrence, and overall survival were recorded. Radiation response of cervical tumour cell lines after SCCA1 expression or CRISPR/Cas9 knockout was evaluated by clonogenic survival assay.Results:Persistently elevated serum SCCA during definitive CRT was an independent predictor of positive post-therapy FDG-PET/CT (P=0.043), recurrence (P=0.0046) and death (P=0.015). An SCCA1-expressing vector increased radioresistance, while SCCA knock out increased radiosensitivity of cervical tumour cell lines in vitro.Conclusions:Early response assessment with serum SCCA is a powerful prognostic tool. These findings suggest that escalation of therapy in patients with elevated or sustained serum SCCA and molecular targeting of SCCA1 should be considered.

Original languageEnglish (US)
Pages (from-to)72-78
Number of pages7
JournalBritish journal of cancer
Volume118
Issue number1
DOIs
StatePublished - Jan 1 2018

Keywords

  • FDG-PET
  • biomarker
  • chemoradiation
  • radiation resistance
  • serpin

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Markovina, S., Wang, S., Henke, L. E., Luke, C. J., Pak, S. C., Dewees, T., Pfeifer, J. D., Schwarz, J. K., Liu, W., Chen, S., Mutch, D., Wang, X., Powell, M. A., Siegel, B. A., Dehdashti, F., Silverman, G. A., & Grigsby, P. W. (2018). Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer. British journal of cancer, 118(1), 72-78. https://doi.org/10.1038/bjc.2017.390