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

doi:10.1038/bjc.2017.390

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

Quantitative Health Sciences

Research output: Contribution to journal › Article › peer-review

22 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 language	English (US)
Pages (from-to)	72-78
Number of pages	7
Journal	British journal of cancer
Volume	118
Issue number	1
DOIs	https://doi.org/10.1038/bjc.2017.390
State	Published - Jan 1 2018

Keywords

FDG-PET
biomarker
chemoradiation
radiation resistance
serpin

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1038/bjc.2017.390

Cite this

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

Markovina, S, Wang, S, Henke, LE, Luke, CJ, Pak, SC, Dewees, T, Pfeifer, JD, Schwarz, JK, Liu, W, Chen, S, Mutch, D, Wang, X, Powell, MA, Siegel, BA, Dehdashti, F, Silverman, GA & Grigsby, PW 2018, 'Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer', British journal of cancer, vol. 118, no. 1, pp. 72-78. https://doi.org/10.1038/bjc.2017.390

@article{f0df3aef99cb45dcb421f48b948e5f71,

title = "Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer",

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.",

keywords = "FDG-PET, biomarker, chemoradiation, radiation resistance, serpin",

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

year = "2018",

month = jan,

day = "1",

doi = "10.1038/bjc.2017.390",

language = "English (US)",

volume = "118",

pages = "72--78",

journal = "British journal of cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Serum squamous cell carcinoma antigen as an early indicator of response during therapy of cervical cancer

AU - Markovina, Stephanie

AU - Wang, Songyan

AU - Henke, Lauren E.

AU - Luke, Cliff J.

AU - Pak, Stephen C.

AU - Dewees, Todd

AU - Pfeifer, John D.

AU - Schwarz, Julie K.

AU - Liu, Weijun

AU - Chen, Shuai

AU - Mutch, David

AU - Wang, Xiaowei

AU - Powell, Matthew A.

AU - Siegel, Barry A.

AU - Dehdashti, Farrokh

AU - Silverman, Gary A.

AU - Grigsby, Perry W.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - FDG-PET

KW - biomarker

KW - chemoradiation

KW - radiation resistance

KW - serpin

UR - http://www.scopus.com/inward/record.url?scp=85040339802&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040339802&partnerID=8YFLogxK

U2 - 10.1038/bjc.2017.390

DO - 10.1038/bjc.2017.390

M3 - Article

C2 - 29112685

AN - SCOPUS:85040339802

SN - 0007-0920

VL - 118

SP - 72

EP - 78

JO - British journal of cancer

JF - British journal of cancer

IS - 1

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this