RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer
©2023 The Authors; Published by the American Association for Cancer Research..
PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples.
EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated.
RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78-1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33-0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25-0.75; P = 0.003) than RAD51-High status.
CONCLUSIONS: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
|---|---|
| Enthalten in: |
Clinical cancer research : an official journal of the American Association for Cancer Research - 29(2023), 13 vom: 05. Juli, Seite 2466-2479 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Compadre, Amanda J [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
49DFR088MY |
|---|
| Anmerkungen: |
Date Completed 06.07.2023 Date Revised 18.07.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1158/1078-0432.CCR-22-3335 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM356012743 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM356012743 | ||
| 003 | DE-627 | ||
| 005 | 20231226065546.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1158/1078-0432.CCR-22-3335 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1186.xml |
| 035 | |a (DE-627)NLM356012743 | ||
| 035 | |a (NLM)37097615 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Compadre, Amanda J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 06.07.2023 | ||
| 500 | |a Date Revised 18.07.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a ©2023 The Authors; Published by the American Association for Cancer Research. | ||
| 520 | |a PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples | ||
| 520 | |a EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated | ||
| 520 | |a RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78-1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33-0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25-0.75; P = 0.003) than RAD51-High status | ||
| 520 | |a CONCLUSIONS: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Platinum |2 NLM | |
| 650 | 7 | |a 49DFR088MY |2 NLM | |
| 650 | 7 | |a Rad51 Recombinase |2 NLM | |
| 650 | 7 | |a EC 2.7.7.- |2 NLM | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a RAD51 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.7.- |2 NLM | |
| 700 | 1 | |a van Biljon, Lillian N |e verfasserin |4 aut | |
| 700 | 1 | |a Valentine, Mark C |e verfasserin |4 aut | |
| 700 | 1 | |a Llop-Guevara, Alba |e verfasserin |4 aut | |
| 700 | 1 | |a Graham, Emily |e verfasserin |4 aut | |
| 700 | 1 | |a Fashemi, Bisiayo |e verfasserin |4 aut | |
| 700 | 1 | |a Herencia-Ropero, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Kotnik, Emilee N |e verfasserin |4 aut | |
| 700 | 1 | |a Cooper, Isaac |e verfasserin |4 aut | |
| 700 | 1 | |a Harrington, Shariska P |e verfasserin |4 aut | |
| 700 | 1 | |a Kuroki, Lindsay M |e verfasserin |4 aut | |
| 700 | 1 | |a McCourt, Carolyn K |e verfasserin |4 aut | |
| 700 | 1 | |a Hagemann, Andrea R |e verfasserin |4 aut | |
| 700 | 1 | |a Thaker, Premal H |e verfasserin |4 aut | |
| 700 | 1 | |a Mutch, David G |e verfasserin |4 aut | |
| 700 | 1 | |a Powell, Matthew A |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lulu |e verfasserin |4 aut | |
| 700 | 1 | |a Mosammaparast, Nima |e verfasserin |4 aut | |
| 700 | 1 | |a Serra, Violeta |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Peinan |e verfasserin |4 aut | |
| 700 | 1 | |a Lomonosova, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Khabele, Dineo |e verfasserin |4 aut | |
| 700 | 1 | |a Mullen, Mary M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical cancer research : an official journal of the American Association for Cancer Research |d 1995 |g 29(2023), 13 vom: 05. Juli, Seite 2466-2479 |w (DE-627)NLM09444479X |x 1557-3265 |7 nnns |
| 773 | 1 | 8 | |g volume:29 |g year:2023 |g number:13 |g day:05 |g month:07 |g pages:2466-2479 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1158/1078-0432.CCR-22-3335 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 29 |j 2023 |e 13 |b 05 |c 07 |h 2466-2479 | ||