In Situ Protein Expression of RRM1, ERCC1, and BRCA1 in Metastatic Breast Cancer Patients Treated with Gemcitabine-based Chemotherapy

Overview

Journal Cancer Invest

Specialty Oncology

Date 2009 Dec 9

PMID 19968494

Citations 12

Authors

G Metro

Z Zheng

A Fabi

M Schell

B Antoniani

M Mottolese

A N Monteiro

P Vici

S Lara Rivera

D Boulware

F Cognetti

G Bepler

Affiliations

Soon will be listed here.

Abstract

Ribonucleotide reductase 1 (RRM1) is a determinant of gemcitabine efficacy in non-small-cell lung cancer and pancreatic cancer. We investigated the protein levels of RRM1 and two other DNA repair enzymes, ERCC1 and BRCA1, in 55 metastatic breast cancer (MBC) patients undergoing gemcitabine-based chemotherapy. With automated in situ protein quantification (AQUA v1.6), the average scores for RRM1, ERCC1, and BRCA1 ranged from 245.6-2774.1, 74.0-410.3, and 54.4-1833.1, respectively. They were significantly associated with each other (Spearman's rho > or = .36; p < or = .007). Given their pattern of distribution, RRM1 and BRCA1 are potentially suitable markers for clinical decision making in MBC.

Citing Articles

Single-Sample Networks Reveal Intra-Cytoband Co-Expression Hotspots in Breast Cancer Subtypes.

Ponce-Cusi R, Lopez-Sanchez P, Maracaja-Coutinho V, Espinal-Enriquez J Int J Mol Sci. 2024; 25(22).

PMID: 39596229 PMC: 11594411. DOI: 10.3390/ijms252212163.

Clinical analysis of 21-gene recurrence score test in hormone receptor-positive early-stage breast cancer.

Zhu L, Ma N, Wang B, Zhou C, Yan Y, Wang K Oncol Lett. 2019; 17(6):5469-5480.

PMID: 31186766 PMC: 6507352. DOI: 10.3892/ol.2019.10277.

mutation and DNA repair and synthesis genes in non-small-cell lung cancer.

Ludovini V, Ricciuti B, Tofanetti F, Mencaroni C, Giannarelli D, Sidoni A Mol Clin Oncol. 2018; 9(6):689-696.

PMID: 30546903 PMC: 6256170. DOI: 10.3892/mco.2018.1731.

High excision repair cross-complementation group 1 expression is associated with favorable prognostic factors in breast cancer.

Kim D, Lee H, Kim D, Chae S, Sohn J, Kim K Oncol Lett. 2017; 14(4):4995-5003.

PMID: 28943968 PMC: 5594248. DOI: 10.3892/ol.2017.6737.

ERCC1 Expression in Metastatic Triple Negative Breast Cancer Patients Treated with Platinum-Based Chemotherapy.

EL Baiomy M, El Kashef W Asian Pac J Cancer Prev. 2017; 18(2):507-513.

PMID: 28345838 PMC: 5454751. DOI: 10.22034/APJCP.2017.18.2.507.

References

Quinn J, Kennedy R, Mullan P, Gilmore P, Carty M, Johnston P . BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res. 2003; 63(19):6221-8. View

James C, Quinn J, Mullan P, Johnston P, Harkin D . BRCA1, a potential predictive biomarker in the treatment of breast cancer. Oncologist. 2007; 12(2):142-50. DOI: 10.1634/theoncologist.12-2-142. View

Goffin J, Chappuis P, Begin L, Wong N, Brunet J, Hamel N . Impact of germline BRCA1 mutations and overexpression of p53 on prognosis and response to treatment following breast carcinoma: 10-year follow up data. Cancer. 2003; 97(3):527-36. DOI: 10.1002/cncr.11080. View

Oguri T, Achiwa H, Muramatsu H, Ozasa H, Sato S, Shimizu S . The absence of human equilibrative nucleoside transporter 1 expression predicts nonresponse to gemcitabine-containing chemotherapy in non-small cell lung cancer. Cancer Lett. 2007; 256(1):112-9. DOI: 10.1016/j.canlet.2007.06.012. View

Davidson J, Ma L, Flagella M, Geeganage S, Gelbert L, Slapak C . An increase in the expression of ribonucleotide reductase large subunit 1 is associated with gemcitabine resistance in non-small cell lung cancer cell lines. Cancer Res. 2004; 64(11):3761-6. DOI: 10.1158/0008-5472.CAN-03-3363. View

Bosetti C, Bertuccio P, Levi F, Lucchini F, Negri E, La Vecchia C . Cancer mortality in the European Union, 1970-2003, with a joinpoint analysis. Ann Oncol. 2008; 19(4):631-40. DOI: 10.1093/annonc/mdm597. View

Chabalier C, Lamare C, Racca C, Privat M, Valette A, Larminat F . BRCA1 downregulation leads to premature inactivation of spindle checkpoint and confers paclitaxel resistance. Cell Cycle. 2006; 5(9):1001-7. DOI: 10.4161/cc.5.9.2726. View

Bepler G, Sharma S, Cantor A, Gautam A, Haura E, Simon G . RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. J Clin Oncol. 2004; 22(10):1878-85. DOI: 10.1200/JCO.2004.12.002. View

Byrski T, Huzarski T, Dent R, Gronwald J, Zuziak D, Cybulski C . Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat. 2008; 115(2):359-63. DOI: 10.1007/s10549-008-0128-9. View

10.

Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G . DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med. 2007; 356(8):800-8. DOI: 10.1056/NEJMoa065411. View

11.

Lafarge S, Sylvain V, Ferrara M, Bignon Y . Inhibition of BRCA1 leads to increased chemoresistance to microtubule-interfering agents, an effect that involves the JNK pathway. Oncogene. 2001; 20(45):6597-606. DOI: 10.1038/sj.onc.1204812. View

12.

Kennedy R, Quinn J, Mullan P, Johnston P, Harkin D . The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst. 2004; 96(22):1659-68. DOI: 10.1093/jnci/djh312. View

13.

Chappuis P, Goffin J, Wong N, Perret C, Ghadirian P, Tonin P . A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer. J Med Genet. 2002; 39(8):608-10. PMC: 1735193. DOI: 10.1136/jmg.39.8.608. View

14.

Bergman A, Eijk P, Ruiz van Haperen V, Smid K, Veerman G, Hubeek I . In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit M1 as the major determinant. Cancer Res. 2005; 65(20):9510-6. DOI: 10.1158/0008-5472.CAN-05-0989. View

15.

Kim S, Jeong J, Kim M, Cho H, Ju J, Kwon Y . Efficacy of gemcitabine in patients with non-small cell lung cancer according to promoter polymorphisms of the ribonucleotide reductase M1 gene. Clin Cancer Res. 2008; 14(10):3083-8. DOI: 10.1158/1078-0432.CCR-07-4591. View

16.

Lund B, Kristjansen P, Hansen H . Clinical and preclinical activity of 2',2'-difluorodeoxycytidine (gemcitabine). Cancer Treat Rev. 1993; 19(1):45-55. DOI: 10.1016/0305-7372(93)90026-n. View

17.

Olaussen K, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V . DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006; 355(10):983-91. DOI: 10.1056/NEJMoa060570. View

18.

Ceppi P, Volante M, Novello S, Rapa I, Danenberg K, Danenberg P . ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine. Ann Oncol. 2006; 17(12):1818-25. DOI: 10.1093/annonc/mdl300. View

19.

Rosell R, Skrzypski M, Jassem E, Taron M, Bartolucci R, Sanchez J . BRCA1: a novel prognostic factor in resected non-small-cell lung cancer. PLoS One. 2007; 2(11):e1129. PMC: 2042516. DOI: 10.1371/journal.pone.0001129. View

20.

Toschi L, Finocchiaro G, Bartolini S, Gioia V, Cappuzzo F . Role of gemcitabine in cancer therapy. Future Oncol. 2006; 1(1):7-17. DOI: 10.1517/14796694.1.1.7. View