Chfr and paclitaxel sensitivity of ovarian cancer

Andrea E. Wahner Hendrickson; Daniel W. Visscher; Xiaonan Hou; Krista M. Goergen; Hunter J. Atkinson; Thomas G. Beito; Vivian Negron; Wilma L. Lingle; Amy K. Bruzek; Rachel M. Hurley; Jill M. Wagner; Karen S. Flatten; Kevin L. Peterson; Paula A. Schneider; Melissa C. Larson; Matthew J. Maurer; Kimberly R. Kalli; Ann L. Oberg; S. John Weroha; Scott H. Kaufmann

doi:10.3390/cancers13236043

Chfr and paclitaxel sensitivity of ovarian cancer

Andrea E. Wahner Hendrickson, Daniel W. Visscher, Xiaonan Hou, Krista M. Goergen, Hunter J. Atkinson, Thomas G. Beito, Vivian Negron, Wilma L. Lingle, Amy K. Bruzek, Rachel M. Hurley, Jill M. Wagner, Karen S. Flatten, Kevin L. Peterson, Paula A. Schneider, Melissa C. Larson, Matthew J. Maurer, Kimberly R. Kalli, Ann L. Oberg, S. John Weroha, Scott H. Kaufmann

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

Abstract

The poly(ADP‐ribose) binding protein CHFR regulates cellular responses to mitotic stress. The deubiquitinase UBC13, which regulates CHFR levels, has been associated with better overall survival in paclitaxel‐treated ovarian cancer. Despite the extensive use of taxanes in the treatment of ovarian cancer, little is known about expression of CHFR itself in this disease. In the present study, tissue microarrays containing ovarian carcinoma samples from 417 women who underwent initial surgical debulking were stained with anti‐CHFR antibody and scored in a blinded fashion. CHFR levels, expressed as a modified H‐score, were examined for association with histology, grade, time to progression (TTP) and overall survival (OS). In addition, patient‐derived xenografts from 69 ovarian carcinoma patients were examined for CHFR expression and sensitivity to paclitaxel monotherapy. In clinical ovarian cancer specimens, CHFR expression was positively associated with serous histology (p = 0.0048), higher grade (p = 0.000014) and higher stage (p = 0.016). After correction for stage and debulking, there was no significant association between CHFR staining and overall survival (p = 0.62) or time to progression (p = 0.91) in patients with high grade serous cancers treated with platinum/taxane chemotherapy (N = 249). Likewise, no association between CHFR expression and paclitaxel sensitivity was observed in ovarian cancer PDXs treated with paclitaxel monotherapy. Accordingly, differences in CHFR expression are unlikely to play a major role in paclitaxel sensitivity of high grade serous ovarian cancer.

Original language	English (US)
Article number	6043
Journal	Cancers
Volume	13
Issue number	23
DOIs	https://doi.org/10.3390/cancers13236043
State	Published - Dec 1 2021

Keywords

CHFR
Ovarian cancer
Patient‐derived xenografts
Taxanes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.3390/cancers13236043

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Wahner Hendrickson, A. E., Visscher, D. W., Hou, X., Goergen, K. M., Atkinson, H. J., Beito, T. G., Negron, V., Lingle, W. L., Bruzek, A. K., Hurley, R. M., Wagner, J. M., Flatten, K. S., Peterson, K. L., Schneider, P. A., Larson, M. C., Maurer, M. J., Kalli, K. R., Oberg, A. L., Weroha, S. J., & Kaufmann, S. H. (2021). Chfr and paclitaxel sensitivity of ovarian cancer. Cancers, 13(23), Article 6043. https://doi.org/10.3390/cancers13236043

Wahner Hendrickson, AE, Visscher, DW, Hou, X, Goergen, KM, Atkinson, HJ, Beito, TG, Negron, V, Lingle, WL, Bruzek, AK, Hurley, RM, Wagner, JM, Flatten, KS, Peterson, KL, Schneider, PA, Larson, MC, Maurer, MJ, Kalli, KR, Oberg, AL , Weroha, SJ & Kaufmann, SH 2021, 'Chfr and paclitaxel sensitivity of ovarian cancer', Cancers, vol. 13, no. 23, 6043. https://doi.org/10.3390/cancers13236043

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title = "Chfr and paclitaxel sensitivity of ovarian cancer",

abstract = "The poly(ADP‐ribose) binding protein CHFR regulates cellular responses to mitotic stress. The deubiquitinase UBC13, which regulates CHFR levels, has been associated with better overall survival in paclitaxel‐treated ovarian cancer. Despite the extensive use of taxanes in the treatment of ovarian cancer, little is known about expression of CHFR itself in this disease. In the present study, tissue microarrays containing ovarian carcinoma samples from 417 women who underwent initial surgical debulking were stained with anti‐CHFR antibody and scored in a blinded fashion. CHFR levels, expressed as a modified H‐score, were examined for association with histology, grade, time to progression (TTP) and overall survival (OS). In addition, patient‐derived xenografts from 69 ovarian carcinoma patients were examined for CHFR expression and sensitivity to paclitaxel monotherapy. In clinical ovarian cancer specimens, CHFR expression was positively associated with serous histology (p = 0.0048), higher grade (p = 0.000014) and higher stage (p = 0.016). After correction for stage and debulking, there was no significant association between CHFR staining and overall survival (p = 0.62) or time to progression (p = 0.91) in patients with high grade serous cancers treated with platinum/taxane chemotherapy (N = 249). Likewise, no association between CHFR expression and paclitaxel sensitivity was observed in ovarian cancer PDXs treated with paclitaxel monotherapy. Accordingly, differences in CHFR expression are unlikely to play a major role in paclitaxel sensitivity of high grade serous ovarian cancer.",

keywords = "CHFR, Ovarian cancer, Patient‐derived xenografts, Taxanes",

author = "{Wahner Hendrickson}, {Andrea E.} and Visscher, {Daniel W.} and Xiaonan Hou and Goergen, {Krista M.} and Atkinson, {Hunter J.} and Beito, {Thomas G.} and Vivian Negron and Lingle, {Wilma L.} and Bruzek, {Amy K.} and Hurley, {Rachel M.} and Wagner, {Jill M.} and Flatten, {Karen S.} and Peterson, {Kevin L.} and Schneider, {Paula A.} and Larson, {Melissa C.} and Maurer, {Matthew J.} and Kalli, {Kimberly R.} and Oberg, {Ann L.} and Weroha, {S. John} and Kaufmann, {Scott H.}",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = dec,

day = "1",

doi = "10.3390/cancers13236043",

language = "English (US)",

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AU - Wahner Hendrickson, Andrea E.

AU - Visscher, Daniel W.

AU - Hou, Xiaonan

AU - Goergen, Krista M.

AU - Atkinson, Hunter J.

AU - Beito, Thomas G.

AU - Negron, Vivian

AU - Lingle, Wilma L.

AU - Bruzek, Amy K.

AU - Hurley, Rachel M.

AU - Wagner, Jill M.

AU - Flatten, Karen S.

AU - Peterson, Kevin L.

AU - Schneider, Paula A.

AU - Larson, Melissa C.

AU - Maurer, Matthew J.

AU - Kalli, Kimberly R.

AU - Oberg, Ann L.

AU - Weroha, S. John

AU - Kaufmann, Scott H.

PY - 2021/12/1

Y1 - 2021/12/1

N2 - The poly(ADP‐ribose) binding protein CHFR regulates cellular responses to mitotic stress. The deubiquitinase UBC13, which regulates CHFR levels, has been associated with better overall survival in paclitaxel‐treated ovarian cancer. Despite the extensive use of taxanes in the treatment of ovarian cancer, little is known about expression of CHFR itself in this disease. In the present study, tissue microarrays containing ovarian carcinoma samples from 417 women who underwent initial surgical debulking were stained with anti‐CHFR antibody and scored in a blinded fashion. CHFR levels, expressed as a modified H‐score, were examined for association with histology, grade, time to progression (TTP) and overall survival (OS). In addition, patient‐derived xenografts from 69 ovarian carcinoma patients were examined for CHFR expression and sensitivity to paclitaxel monotherapy. In clinical ovarian cancer specimens, CHFR expression was positively associated with serous histology (p = 0.0048), higher grade (p = 0.000014) and higher stage (p = 0.016). After correction for stage and debulking, there was no significant association between CHFR staining and overall survival (p = 0.62) or time to progression (p = 0.91) in patients with high grade serous cancers treated with platinum/taxane chemotherapy (N = 249). Likewise, no association between CHFR expression and paclitaxel sensitivity was observed in ovarian cancer PDXs treated with paclitaxel monotherapy. Accordingly, differences in CHFR expression are unlikely to play a major role in paclitaxel sensitivity of high grade serous ovarian cancer.

AB - The poly(ADP‐ribose) binding protein CHFR regulates cellular responses to mitotic stress. The deubiquitinase UBC13, which regulates CHFR levels, has been associated with better overall survival in paclitaxel‐treated ovarian cancer. Despite the extensive use of taxanes in the treatment of ovarian cancer, little is known about expression of CHFR itself in this disease. In the present study, tissue microarrays containing ovarian carcinoma samples from 417 women who underwent initial surgical debulking were stained with anti‐CHFR antibody and scored in a blinded fashion. CHFR levels, expressed as a modified H‐score, were examined for association with histology, grade, time to progression (TTP) and overall survival (OS). In addition, patient‐derived xenografts from 69 ovarian carcinoma patients were examined for CHFR expression and sensitivity to paclitaxel monotherapy. In clinical ovarian cancer specimens, CHFR expression was positively associated with serous histology (p = 0.0048), higher grade (p = 0.000014) and higher stage (p = 0.016). After correction for stage and debulking, there was no significant association between CHFR staining and overall survival (p = 0.62) or time to progression (p = 0.91) in patients with high grade serous cancers treated with platinum/taxane chemotherapy (N = 249). Likewise, no association between CHFR expression and paclitaxel sensitivity was observed in ovarian cancer PDXs treated with paclitaxel monotherapy. Accordingly, differences in CHFR expression are unlikely to play a major role in paclitaxel sensitivity of high grade serous ovarian cancer.

KW - CHFR

KW - Ovarian cancer

KW - Patient‐derived xenografts

KW - Taxanes

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DO - 10.3390/cancers13236043

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VL - 13

JO - Cancers

JF - Cancers

IS - 23

M1 - 6043

ER -

Chfr and paclitaxel sensitivity of ovarian cancer

Abstract

Keywords

ASJC Scopus subject areas

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