CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes of epithelial ovarian cancer

Bipradeb Singha, Sandra L. Harper, Aaron R. Goldman, Benjamin G. Bitler, Katherine Aird, Mark E. Borowsky, Mark G. Cadungog, Qin Liu, Rugang Zhang, Stephanie Jean, Ronny Drapkin, David W. Speicher

Research output: Contribution to journalArticle

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Abstract

New plasma and tissue biomarkers of epithelial ovarian cancer (EOC) could improve early diagnosis and post-diagnosis clinical management. Here we investigated tissue staining and tissue secretion of CLIC1 and CLIC4 across EOC subtypes. CLIC1 and CLIC4 are two promising biomarkers we previously showed were elevated in EOC patient sera. Individually, CLIC1 or CLIC4 stained larger percentages of malignant tumors across all EOC subtypes compared with CA125, particularly early stage and mucinous tumors. CLIC4 also stained benign tumors but staining was limited to nuclei; whereas malignant tumors showed diffuse cellular staining of stromal and tumor cells. Both proteins were shed by all EOC subtypes tumors in short term organ culture at more consistent levels than CA125, supporting their potential as pan-subtype serum and tissue biomarkers. Elevated CLIC4 expression, but not CLIC1 expression, was a negative indicator of patient survival, and CLIC4 knockdown in cultured cells decreased cell proliferation and migration indicating a potential role in tumor progression. These results suggest CLIC1 and CLIC4 are promising serum and tissue biomarkers as well as potential therapeutic targets for all EOC subtypes. This justifies development of high throughput serum/plasma biomarker assays to evaluate utility of a biomarker panel consisting of CLIC1, CLIC4 and CA125.

Original languageEnglish (US)
Article number14725
JournalScientific reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Biomarkers
Neoplasms
Staining and Labeling
Serum
Organ Culture Techniques
Stromal Cells
Ovarian epithelial cancer
Cell Movement
Early Diagnosis
Cultured Cells
Cell Proliferation
Survival
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Singha, B., Harper, S. L., Goldman, A. R., Bitler, B. G., Aird, K., Borowsky, M. E., ... Speicher, D. W. (2018). CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes of epithelial ovarian cancer. Scientific reports, 8(1), [14725]. https://doi.org/10.1038/s41598-018-32885-2
Singha, Bipradeb ; Harper, Sandra L. ; Goldman, Aaron R. ; Bitler, Benjamin G. ; Aird, Katherine ; Borowsky, Mark E. ; Cadungog, Mark G. ; Liu, Qin ; Zhang, Rugang ; Jean, Stephanie ; Drapkin, Ronny ; Speicher, David W. / CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes of epithelial ovarian cancer. In: Scientific reports. 2018 ; Vol. 8, No. 1.
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abstract = "New plasma and tissue biomarkers of epithelial ovarian cancer (EOC) could improve early diagnosis and post-diagnosis clinical management. Here we investigated tissue staining and tissue secretion of CLIC1 and CLIC4 across EOC subtypes. CLIC1 and CLIC4 are two promising biomarkers we previously showed were elevated in EOC patient sera. Individually, CLIC1 or CLIC4 stained larger percentages of malignant tumors across all EOC subtypes compared with CA125, particularly early stage and mucinous tumors. CLIC4 also stained benign tumors but staining was limited to nuclei; whereas malignant tumors showed diffuse cellular staining of stromal and tumor cells. Both proteins were shed by all EOC subtypes tumors in short term organ culture at more consistent levels than CA125, supporting their potential as pan-subtype serum and tissue biomarkers. Elevated CLIC4 expression, but not CLIC1 expression, was a negative indicator of patient survival, and CLIC4 knockdown in cultured cells decreased cell proliferation and migration indicating a potential role in tumor progression. These results suggest CLIC1 and CLIC4 are promising serum and tissue biomarkers as well as potential therapeutic targets for all EOC subtypes. This justifies development of high throughput serum/plasma biomarker assays to evaluate utility of a biomarker panel consisting of CLIC1, CLIC4 and CA125.",
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Singha, B, Harper, SL, Goldman, AR, Bitler, BG, Aird, K, Borowsky, ME, Cadungog, MG, Liu, Q, Zhang, R, Jean, S, Drapkin, R & Speicher, DW 2018, 'CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes of epithelial ovarian cancer', Scientific reports, vol. 8, no. 1, 14725. https://doi.org/10.1038/s41598-018-32885-2

CLIC1 and CLIC4 complement CA125 as a diagnostic biomarker panel for all subtypes of epithelial ovarian cancer. / Singha, Bipradeb; Harper, Sandra L.; Goldman, Aaron R.; Bitler, Benjamin G.; Aird, Katherine; Borowsky, Mark E.; Cadungog, Mark G.; Liu, Qin; Zhang, Rugang; Jean, Stephanie; Drapkin, Ronny; Speicher, David W.

In: Scientific reports, Vol. 8, No. 1, 14725, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Borowsky, Mark E.

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AU - Jean, Stephanie

AU - Drapkin, Ronny

AU - Speicher, David W.

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