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Article

ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan

  • Authors:
    • Hoang Dinh Tuy
    • Hisanori Shiomi
    • Ken Ichi Mukaisho
    • Shigeyuki Naka
    • Tomoharu Shimizu
    • Hiromichi Sonoda
    • Eiji Mekata
    • Yoshihiro Endo
    • Yoshimasa Kurumi
    • Hiroyuki Sugihara
    • Masaji Tani
    • Tohru Tani
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan, Department of Pathology, Shiga University of Medical Science, Otsu, Shiga 520‑2192, Japan
  • Pages: 2752-2760
    |
    Published online on: August 3, 2016
       https://doi.org/10.3892/ol.2016.4937
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Abstract

Irinotecan is a key drug for patients with advanced and recurrent colorectal carcinoma. However, the efficacy of irinotecan is not sufficient; partly, as there is no useful marker to predict chemosensitivity to the drug. The aim of the present study was to evaluate whether the expression levels of adenosine triphosphate‑binding cassette sub‑family G (WHITE) member 2 (Junior blood group) (ABCG2) in primary colorectal tumors predict chemoresistance to irinotecan. Using the resected primary tumor specimens of 189 patients with colorectal cancer, the association between the immunohistochemical expression of ABCG2 protein and the results of the collagen gel droplet embedded culture drug sensitivity test, performed to evaluate the chemosensitivity to SN‑38 (an active metabolite of irinotecan), was investigated. Among the 189 patients, 17 received irinotecan‑based chemotherapy, and their responses and progression‑free survival (PFS) were analyzed. The tumors of patients with increased ABCG2 expression accounted for 60% of the tumors examined, and were significantly more resistant to SN‑38, compared with patients with low ABCG2 expression (P<0.001). In a multivariate logistic regression analysis, increased expression of ABCG2 protein was an independent and significant predictor of resistance to SN‑38, increasing the risk of resistance by 12‑fold. Increased expression of ABCG2 and a low sensitivity to SN‑38 was significantly associated with resistance to irinotecan‑based chemotherapy (P=0.01 and 0.028, respectively). The median PFS of patients with increased expression of ABCG2 was significantly shorter, compared with patients with low expression levels of ABCG2 (104 vs. 242 days; P=0.047). The increased immunohistochemical expression of ABCG2 in primary tumors may be a useful predictive biomarker of resistance to irinotecan‑based chemotherapy for patients with recurrent or metastatic colorectal cancer.
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1 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Benson AB, Bekaii-Saab T, Chan E, Chen YJ, Choti MA, Cooper HS, Engstrom PF, Enzinger PC, Fakih MG, Fenton MJ, et al: National Comprehensive Cancer Network: Localized colon cancer, version 3.2013: Featured updates to the NCCN Guidelines. J Natl Compr Canc Netw. 11:519–528. 2013.PubMed/NCBI

3 

Pritchard CC and Grady WM: Colorectal cancer molecular biology moves into clinical practice. Gut. 60:116–129. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Winder T and Lenz HJ: Molecular predictive and prognostic markers in colon cancer. Cancer Treat Rev. 36:550–556. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Vanhoefer U, Harstrick A, Achterrath W, Cao S, Seeber S and Rustum YM: Irinotecan in the treatment of colorectal cancer: Clinical overview. J Clin Oncol. 19:1501–1518. 2001.PubMed/NCBI

6 

Xu Y and Villalona-Calero MA: Irinotecan: Mechanisms of tumor resistance and novel strategies for modulating its activity. Ann Oncol. 13:1841–1851. 2002. View Article : Google Scholar : PubMed/NCBI

7 

Allen WL, Coyle VM and Johnston PG: Predicting the outcome of chemotherapy for colorectal cancer. Curr Opin Pharmacol. 6:332–336. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Leslie EM, Deeley RG and Cole SP: Multidrug resistance proteins: Role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicol Appl Pharmacol. 204:216–237. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Han B and Zhang JT: Multidrug resistance in cancer chemotherapy and xenobiotic protection mediated by the half ATP-binding cassette transporter ABCG2. Curr Med Chem Anticancer Agents. 4:31–42. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Benderra Z, Faussat AM, Sayada L, Perrot JY, Tang R, Chaoui D, Morjani H, Marzac C, Marie JP and Legrand O: MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia. Clin Cancer Res. 11:7764–7772. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Burger H, Foekens JA, Look MP, Meijer-van Gelder ME, Klijn JG, Wiemer EA, Stoter G and Nooter K: RNA expression of breast cancer resistance protein, lung resistance-related protein, multidrug resistance-associated proteins 1 and 2, and multidrug resistance gene 1 in breast cancer: Correlation with chemotherapeutic response. Clin Cancer Res. 9:827–836. 2003.PubMed/NCBI

12 

Friedrich RE, Punke C and Reymann A: Expression of multi-drug resistance genes (mdr1, mrp1, bcrp) in primary oral squamous cell carcinoma. In Vivo. 18:133–147. 2004.PubMed/NCBI

13 

Tsunoda S, Okumura T, Ito T, Kondo K, Ortiz C, Tanaka E, Watanabe G, Itami A, Sakai Y and Shimada Y: ABCG2 expression is an independent unfavorable prognostic factor in esophageal squamous cell carcinoma. Oncology. 71:251–258. 2006. View Article : Google Scholar : PubMed/NCBI

14 

Kim YH, Ishii G, Goto K, Ota S, Kubota K, Murata Y, Mishima M, Saijo N, Nishiwaki Y and Ochiai A: Expression of breast cancer resistance protein is associated with a poor clinical outcome in patients with small-cell lung cancer. Lung Cancer. 65:105–111. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Robey RW, To KK, Polgar O, Dohse M, Fetsch P, Dean M and Bates SE: ABCG2: A perspective. Adv Drug Deliv Rev. 61:3–13. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Gupta N, Martin PM, Miyauchi S, Ananth S, Herdman AV, Martindale RG, Podolsky R and Ganapathy V: Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer. Biochem Biophys Res Commun. 343:571–577. 2006. View Article : Google Scholar : PubMed/NCBI

17 

Candeil L, Gourdier I, Peyron D, Vezzio N, Copois V, Bibeau F, Orsetti B, Scheffer GL, Ychou M, Khan QA, et al: ABCG2 overexpression in colon cancer cells resistant to SN-38 and in irinotecan-treated metastases. Int J Cancer. 109:848–854. 2004. View Article : Google Scholar : PubMed/NCBI

18 

Muro K, Boku N, Shimada Y, Tsuji A, Sameshima S, Baba H, Satoh T, Denda T, Ina K, Nishina T, et al: Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: A randomised phase 2/3 non-inferiority study (FIRIS study). Lancet Oncol. 11:853–860. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, et al: New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 45:228–247. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Kobayashi H: Development of a new in vitro chemosensitivity test using collagen gel droplet embedded culture and image analysis for clinical usefulness. Recent Results Cancer Res. 161:48–61. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Sinicrope FA, Ruan SB, Cleary KR, Stephens LC, Lee JJ and Levin B: Bcl-2 and p53 oncoprotein expression during colorectal tumorigenesis. Cancer Res. 55:237–241. 1995.PubMed/NCBI

22 

Hosmer DW and Lemeshow S: Applied Logistic Regression. Shewhart WA and Wilks SS: 2nd. John Wiley & Sons, Inc.; New York: pp. 31–46. 2000

23 

Kawabata S, Oka M, Shiozawa K, Tsukamoto K, Nakatomi K, Soda H, Fukuda M, Ikegami Y, Sugahara K, Yamada Y, et al: Breast cancer resistance protein directly confers SN-38 resistance of lung cancer cells. Biochem Biophys Res Commun. 280:1216–1223. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Robey RW, Ierano C, Zhan Z and Bates SE: The challenge of exploiting ABCG2 in the clinic. Curr Pharm Biotechnol. 12:595–608. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Mo W and Zhang JT: Human ABCG2: Structure, function and its role in multidrug resistance. Int J Biochem Mol Biol. 3:1–27. 2012.PubMed/NCBI

26 

Dietrich CG, Vehr AK, Martin IV, Gassler N, Rath T, Roeb E, Schmitt J, Trautwein C and Geier A: Downregulation of breast cancer resistance protein in colon adenomas reduces cellular xenobiotic resistance and leads to accumulation of a food-derived carcinogen. Int J Cancer. 129:546–552. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Glasgow SC, Yu J, Carvalho LP, Shannon WD, Fleshman JW and McLeod HL: Unfavourable expression of pharmacologic markers in mucinous colorectal cancer. Br J Cancer. 92:259–264. 2005.PubMed/NCBI

28 

Xiang L, Su P, Xia S, Liu Z, Wang Y, Gao P and Zhou G: ABCG2 is associated with HER-2 expression, lymph node metastasis and clinical stage in breast invasive ductal carcinoma. Diagn Pathol. 6:902011. View Article : Google Scholar : PubMed/NCBI

29 

Jin Y, Bin ZQ, Qiang H, Liang C, Hua C, Jun D, Dong WA and Qing L: ABCG2 is related with the grade of glioma and resistance to mitoxantone, a chemotherapeutic drug for glioma. J Cancer Res Clin Oncol. 135:1369–1376. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Gongora C, VezzioVie N, Tuduri S, Denis V, Causse A, Auzanneau C, CollodBeroud G, Coquelle A, Pasero P, Pourquier P, et al: New Topoisomerase I mutations are associated with resistance to camptothecin. Mol Cancer. 10:642011. View Article : Google Scholar : PubMed/NCBI

31 

DelRio M, Molina F, BascoulMollevi C, Copois V, Bibeau F, Chalbos P, Bareil C, Kramar A, Salvetat N, Fraslon C, et al: Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan. J Clin Oncol. 25:773–780. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Lansiaux A, BrasGoncalves RA, Rosty C, LaurentPuig P, Poupon MF and Bailly C: Topoisomerase I-DNA covalent complexes in human colorectal cancer xenografts with different p53 and microsatellite instability status: Relation with their sensitivity to CTP-11. Anticancer Res. 21:471–476. 2001.PubMed/NCBI

33 

Paradiso A, Xu J, Mangia A, Chiriatti A, Simone G, Zito A, Montemurro S, Giuliani F, Maiello E and Colucci G: Topoisomerase-I, thymidylate synthase primary tumour expression and clinical efficacy of 5-FU/CPT-11 chemotherapy in advanced colorectal cancer patients. Int J Cancer. 111:252–258. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Tuy HD, Shiomi H, Mukaisho KI, Naka S, Shimizu T, Sonoda H, Mekata E, Endo Y, Kurumi Y, Sugihara H, Sugihara H, et al: ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan. Oncol Lett 12: 2752-2760, 2016.
APA
Tuy, H.D., Shiomi, H., Mukaisho, K.I., Naka, S., Shimizu, T., Sonoda, H. ... Tani, T. (2016). ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan. Oncology Letters, 12, 2752-2760. https://doi.org/10.3892/ol.2016.4937
MLA
Tuy, H. D., Shiomi, H., Mukaisho, K. I., Naka, S., Shimizu, T., Sonoda, H., Mekata, E., Endo, Y., Kurumi, Y., Sugihara, H., Tani, M., Tani, T."ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan". Oncology Letters 12.4 (2016): 2752-2760.
Chicago
Tuy, H. D., Shiomi, H., Mukaisho, K. I., Naka, S., Shimizu, T., Sonoda, H., Mekata, E., Endo, Y., Kurumi, Y., Sugihara, H., Tani, M., Tani, T."ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan". Oncology Letters 12, no. 4 (2016): 2752-2760. https://doi.org/10.3892/ol.2016.4937
Copy and paste a formatted citation
x
Spandidos Publications style
Tuy HD, Shiomi H, Mukaisho KI, Naka S, Shimizu T, Sonoda H, Mekata E, Endo Y, Kurumi Y, Sugihara H, Sugihara H, et al: ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan. Oncol Lett 12: 2752-2760, 2016.
APA
Tuy, H.D., Shiomi, H., Mukaisho, K.I., Naka, S., Shimizu, T., Sonoda, H. ... Tani, T. (2016). ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan. Oncology Letters, 12, 2752-2760. https://doi.org/10.3892/ol.2016.4937
MLA
Tuy, H. D., Shiomi, H., Mukaisho, K. I., Naka, S., Shimizu, T., Sonoda, H., Mekata, E., Endo, Y., Kurumi, Y., Sugihara, H., Tani, M., Tani, T."ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan". Oncology Letters 12.4 (2016): 2752-2760.
Chicago
Tuy, H. D., Shiomi, H., Mukaisho, K. I., Naka, S., Shimizu, T., Sonoda, H., Mekata, E., Endo, Y., Kurumi, Y., Sugihara, H., Tani, M., Tani, T."ABCG2 expression in colorectal adenocarcinomas may predict resistance to irinotecan". Oncology Letters 12, no. 4 (2016): 2752-2760. https://doi.org/10.3892/ol.2016.4937
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