DNA Methylation Status As a Biomarker of Anti-epidermal Growth Factor Receptor Treatment for Metastatic Colorectal Cancer

Overview

Journal Cancer Sci

Specialty Oncology

Date 2015 Oct 2

PMID 26426205

Citations 17

Authors

Kota Ouchi

Shin Takahashi

Yasuhide Yamada

Shingo Tsuji

Kenji Tatsuno

Hidekazu Takahashi

Naoki Takahashi

Masanobu Takahashi

Hideki Shimodaira

Hiroyuki Aburatani

Chikashi Ishioka

Affiliations

Soon will be listed here.

Abstract

Anti-epidermal growth factor receptor (EGFR) treatment is an effective option for metastatic colorectal cancer (CRC) treatment. However, there are few reliable biomarkers to predict the clinical response to anti-EGFR treatment. We investigated the genome-wide DNA methylation status in metastatic colorectal cancer to identify associations between the methylation status and clinical response to anti-EGFR antibody. We retrospectively reviewed the medical records of 97 patients (45 patients for the first cohort and 52 patients for the second cohort) who received anti-EGFR treatment for KRAS wild-type metastatic CRC. Then we analyzed the associations between genome-wide DNA methylation status and clinical response to anti-EGFR treatment, and evaluated the predictive power and value of the methylation status statistically. As a result, each cohort was classified into highly methylated CRC and low methylated CRC subgroups by unsupervised clustering analyses. In the first cohort, clinical outcomes were significantly better in the low methylated CRC subgroup than in the highly methylated CRC subgroup (response rate, 35.7% vs 6.3%, P = 0.03; disease control rate, 75% vs 31.3%, P = 0.005; hazard ratio for progression-free survival, 0.27; 95% confidence interval, 0.13-0.57, P < 0.001; overall survival, 0.19; 95% confidence interval, 0.06-0.54, P < 0.001). These results were reproducible in the second cohort. The genome-wide methylation status was a predictive factor of progression-free survival and overall survival independently of RAS mutation status. In conclusion, we found that the genome-wide DNA methylation status is a powerful epigenetic predictor of anti-EGFR treatment in patients with KRAS wild-type metastatic colorectal cancer (UMIN000005490).

Citing Articles

Genome-wide DNA methylation status is a predictor of the efficacy of anti-EGFR antibodies in the second-line treatment of metastatic colorectal cancer: Translational research of the EPIC trial.

Ouchi K, Takahashi S, Sasaki K, Yoshida Y, Taniguchi S, Kasahara Y Int J Colorectal Dis. 2024; 39(1):89.

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Novel DNA methylation-based epigenetic signatures in colorectal cancer from peripheral blood leukocytes.

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Phase II study of biweekly cetuximab plus mFOLFOX6 or mFOLFIRI as second-line treatment for metastatic colorectal cancer and exploratory analysis of associations between DNA methylation status and the efficacy of the anti-EGFR antibody: T-CORE1201.

Takahashi S, Ouchi K, Sakamoto Y, Mori T, Shimodaira H, Takahashi M J Gastrointest Oncol. 2023; 14(2):676-691.

PMID: 37201044 PMC: 10186538. DOI: 10.21037/jgo-22-862.

Effect of DNA methylation status on first-line anti-epidermal growth factor receptor treatment in patients with metastatic colorectal cancer.

Osumi H, Ouchi K, Shinozaki E, Takahashi S, Ooki A, Nakayama I Int J Colorectal Dis. 2022; 37(6):1439-1447.

PMID: 35612620 DOI: 10.1007/s00384-022-04177-9.

References

Dahlin A, Palmqvist R, Henriksson M, Jacobsson M, Eklof V, Rutegard J . The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status. Clin Cancer Res. 2010; 16(6):1845-55. DOI: 10.1158/1078-0432.CCR-09-2594. View

Van Cutsem E, Oliveira J . Advanced colorectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2009; 20 Suppl 4:61-3. DOI: 10.1093/annonc/mdp130. View

Tournigand C, Andre T, Achille E, Lledo G, Flesh M, Mery-Mignard D . FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. J Clin Oncol. 2003; 22(2):229-37. DOI: 10.1200/JCO.2004.05.113. View

Ouchi K, Takahashi S, Yamada Y, Tsuji S, Tatsuno K, Takahashi H . DNA methylation status as a biomarker of anti-epidermal growth factor receptor treatment for metastatic colorectal cancer. Cancer Sci. 2015; 106(12):1722-9. PMC: 4714671. DOI: 10.1111/cas.12827. View

Jemal A, Bray F, Center M, Ferlay J, Ward E, Forman D . Global cancer statistics. CA Cancer J Clin. 2011; 61(2):69-90. DOI: 10.3322/caac.20107. View

Hinoue T, Weisenberger D, Lange C, Shen H, Byun H, van den Berg D . Genome-scale analysis of aberrant DNA methylation in colorectal cancer. Genome Res. 2011; 22(2):271-82. PMC: 3266034. DOI: 10.1101/gr.117523.110. View

Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B . Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007; 25(13):1658-64. DOI: 10.1200/JCO.2006.08.1620. View

Yagi K, Akagi K, Hayashi H, Nagae G, Tsuji S, Isagawa T . Three DNA methylation epigenotypes in human colorectal cancer. Clin Cancer Res. 2009; 16(1):21-33. DOI: 10.1158/1078-0432.CCR-09-2006. View

Torlakovic E, Gomez J, Driman D, Parfitt J, Wang C, Benerjee T . Sessile serrated adenoma (SSA) vs. traditional serrated adenoma (TSA). Am J Surg Pathol. 2007; 32(1):21-9. DOI: 10.1097/PAS.0b013e318157f002. View

10.

Schwartzberg L, Rivera F, Karthaus M, Fasola G, Canon J, Hecht J . PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic.... J Clin Oncol. 2014; 32(21):2240-7. DOI: 10.1200/JCO.2013.53.2473. View

11.

Weisenberger D, Trinh B, Campan M, Sharma S, Long T, Ananthnarayan S . DNA methylation analysis by digital bisulfite genomic sequencing and digital MethyLight. Nucleic Acids Res. 2008; 36(14):4689-98. PMC: 2504308. DOI: 10.1093/nar/gkn455. View

12.

Saltz L, Clarke S, Diaz-Rubio E, Scheithauer W, Figer A, Wong R . Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008; 26(12):2013-9. DOI: 10.1200/JCO.2007.14.9930. View

13.

Douillard J, Oliner K, Siena S, Tabernero J, Burkes R, Barugel M . Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013; 369(11):1023-34. DOI: 10.1056/NEJMoa1305275. View

14.

Peeters M, Price T, Cervantes A, Sobrero A, Ducreux M, Hotko Y . Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010; 28(31):4706-13. DOI: 10.1200/JCO.2009.27.6055. View

15.

Di Nicolantonio F, Martini M, Molinari F, Sartore-Bianchi A, Arena S, Saletti P . Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol. 2008; 26(35):5705-12. DOI: 10.1200/JCO.2008.18.0786. View

16.

de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J . Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000; 18(16):2938-47. DOI: 10.1200/JCO.2000.18.16.2938. View

17.

Garrido-Laguna I, McGregor K, Wade M, Weis J, Gilcrease W, Burr L . A phase I/II study of decitabine in combination with panitumumab in patients with wild-type (wt) KRAS metastatic colorectal cancer. Invest New Drugs. 2013; 31(5):1257-64. DOI: 10.1007/s10637-013-9947-6. View

18.

Samowitz W, Albertsen H, Sweeney C, Herrick J, Caan B, Anderson K . Association of smoking, CpG island methylator phenotype, and V600E BRAF mutations in colon cancer. J Natl Cancer Inst. 2006; 98(23):1731-8. DOI: 10.1093/jnci/djj468. View

19.

Douillard J, Cunningham D, Roth A, Navarro M, James R, Karasek P . Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000; 355(9209):1041-7. DOI: 10.1016/s0140-6736(00)02034-1. View

20.

Goldberg R, Sargent D, Morton R, Fuchs C, Ramanathan R, Williamson S . A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer. J Clin Oncol. 2003; 22(1):23-30. DOI: 10.1200/JCO.2004.09.046. View