Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer

Hisayoshi Igarashi, Hiroyoshi Kurihara, Kei Mitsuhashi, Miki Ito, Hiroyuki Okuda, Shinichi Kanno, Takafumi Naito, Shinji Yoshii, Hiroaki Takahashi, Takaya Kusumi, Tadashi Hasegawa, Yasutaka Sukawa, Yasushi Adachi, Kenji Okita, Koichi Hirata, Yu Imamura, Yoshifumi Baba, Kohzoh Imai, Hiromu Suzuki, Hiroyuki Yamamoto & 2 others Katsuhiko Nosho, Yasuhisa Shinomura

Research output: Contribution to journalArticle

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Abstract

Background: Gene mutations in the pathway downstream of epidermal growth factor receptor (EGFR) are considered to induce resistance to anti-EGFR therapy in colorectal cancer (CRC). We recently reported that microRNA-31 (miR-31)-5p may regulate BRAF activation and play a role in the signaling pathway downstream of EGFR in CRC. Therefore, we hypothesized that miR-31-5p can be a useful biomarker for anti-EGFR therapy in CRC. Methods: We evaluated miR-31-5p expression and gene mutations [KRAS (codon 61 or 146), NRAS (codon 12, 13, or 61), and BRAF (V600E)] in the EGFR downstream pathway in 102 CRC patients harboring KRAS (codon 12 or 13) wild-type who were treated with anti-EGFR therapeutics. Progression-free survival (PFS) and overall survival (OS) were evaluated. Results: KRAS (codon 61 or 146), NRAS, and BRAF mutations were detected in 6.9, 6.9, and 5.9 % patients, respectively. Compared with CRCs with at least one mutation (n = 20), significantly better PFS (P = 0.0003) but insignificantly better OS were observed in CRCs harboring all wild-type genes (KRAS, NRAS, and BRAF). High miR-31-5p expression was identified in 11 % (n = 11) patients and was significantly associated with shorter PFS (P = 0.003). In CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS (P = 0.027). Conclusions: High miR-31-5p expression was associated with shorter PFS in patients with CRC treated with anti-EGFR therapeutics. Moreover, in CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS, suggesting that it may be a useful and additional prognostic biomarker for anti-EGFR therapy.

Original languageEnglish
Pages (from-to)2640-2648
Number of pages9
JournalAnnals of Surgical Oncology
Volume22
Issue number8
DOIs
Publication statusPublished - 2014 Dec 4
Externally publishedYes

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MicroRNAs
Epidermal Growth Factor Receptor
Colorectal Neoplasms
Disease-Free Survival
Codon
Mutation
Therapeutics
Genes
Biomarkers
Survival
Gene Expression

ASJC Scopus subject areas

  • Surgery
  • Oncology

Cite this

Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer. / Igarashi, Hisayoshi; Kurihara, Hiroyoshi; Mitsuhashi, Kei; Ito, Miki; Okuda, Hiroyuki; Kanno, Shinichi; Naito, Takafumi; Yoshii, Shinji; Takahashi, Hiroaki; Kusumi, Takaya; Hasegawa, Tadashi; Sukawa, Yasutaka; Adachi, Yasushi; Okita, Kenji; Hirata, Koichi; Imamura, Yu; Baba, Yoshifumi; Imai, Kohzoh; Suzuki, Hiromu; Yamamoto, Hiroyuki; Nosho, Katsuhiko; Shinomura, Yasuhisa.

In: Annals of Surgical Oncology, Vol. 22, No. 8, 04.12.2014, p. 2640-2648.

Research output: Contribution to journalArticle

Igarashi, H, Kurihara, H, Mitsuhashi, K, Ito, M, Okuda, H, Kanno, S, Naito, T, Yoshii, S, Takahashi, H, Kusumi, T, Hasegawa, T, Sukawa, Y, Adachi, Y, Okita, K, Hirata, K, Imamura, Y, Baba, Y, Imai, K, Suzuki, H, Yamamoto, H, Nosho, K & Shinomura, Y 2014, 'Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer', Annals of Surgical Oncology, vol. 22, no. 8, pp. 2640-2648. https://doi.org/10.1245/s10434-014-4264-7
Igarashi, Hisayoshi ; Kurihara, Hiroyoshi ; Mitsuhashi, Kei ; Ito, Miki ; Okuda, Hiroyuki ; Kanno, Shinichi ; Naito, Takafumi ; Yoshii, Shinji ; Takahashi, Hiroaki ; Kusumi, Takaya ; Hasegawa, Tadashi ; Sukawa, Yasutaka ; Adachi, Yasushi ; Okita, Kenji ; Hirata, Koichi ; Imamura, Yu ; Baba, Yoshifumi ; Imai, Kohzoh ; Suzuki, Hiromu ; Yamamoto, Hiroyuki ; Nosho, Katsuhiko ; Shinomura, Yasuhisa. / Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer. In: Annals of Surgical Oncology. 2014 ; Vol. 22, No. 8. pp. 2640-2648.
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abstract = "Background: Gene mutations in the pathway downstream of epidermal growth factor receptor (EGFR) are considered to induce resistance to anti-EGFR therapy in colorectal cancer (CRC). We recently reported that microRNA-31 (miR-31)-5p may regulate BRAF activation and play a role in the signaling pathway downstream of EGFR in CRC. Therefore, we hypothesized that miR-31-5p can be a useful biomarker for anti-EGFR therapy in CRC. Methods: We evaluated miR-31-5p expression and gene mutations [KRAS (codon 61 or 146), NRAS (codon 12, 13, or 61), and BRAF (V600E)] in the EGFR downstream pathway in 102 CRC patients harboring KRAS (codon 12 or 13) wild-type who were treated with anti-EGFR therapeutics. Progression-free survival (PFS) and overall survival (OS) were evaluated. Results: KRAS (codon 61 or 146), NRAS, and BRAF mutations were detected in 6.9, 6.9, and 5.9 {\%} patients, respectively. Compared with CRCs with at least one mutation (n = 20), significantly better PFS (P = 0.0003) but insignificantly better OS were observed in CRCs harboring all wild-type genes (KRAS, NRAS, and BRAF). High miR-31-5p expression was identified in 11 {\%} (n = 11) patients and was significantly associated with shorter PFS (P = 0.003). In CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS (P = 0.027). Conclusions: High miR-31-5p expression was associated with shorter PFS in patients with CRC treated with anti-EGFR therapeutics. Moreover, in CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS, suggesting that it may be a useful and additional prognostic biomarker for anti-EGFR therapy.",
author = "Hisayoshi Igarashi and Hiroyoshi Kurihara and Kei Mitsuhashi and Miki Ito and Hiroyuki Okuda and Shinichi Kanno and Takafumi Naito and Shinji Yoshii and Hiroaki Takahashi and Takaya Kusumi and Tadashi Hasegawa and Yasutaka Sukawa and Yasushi Adachi and Kenji Okita and Koichi Hirata and Yu Imamura and Yoshifumi Baba and Kohzoh Imai and Hiromu Suzuki and Hiroyuki Yamamoto and Katsuhiko Nosho and Yasuhisa Shinomura",
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TY - JOUR

T1 - Association of MicroRNA-31-5p with Clinical Efficacy of Anti-EGFR Therapy in Patients with Metastatic Colorectal Cancer

AU - Igarashi, Hisayoshi

AU - Kurihara, Hiroyoshi

AU - Mitsuhashi, Kei

AU - Ito, Miki

AU - Okuda, Hiroyuki

AU - Kanno, Shinichi

AU - Naito, Takafumi

AU - Yoshii, Shinji

AU - Takahashi, Hiroaki

AU - Kusumi, Takaya

AU - Hasegawa, Tadashi

AU - Sukawa, Yasutaka

AU - Adachi, Yasushi

AU - Okita, Kenji

AU - Hirata, Koichi

AU - Imamura, Yu

AU - Baba, Yoshifumi

AU - Imai, Kohzoh

AU - Suzuki, Hiromu

AU - Yamamoto, Hiroyuki

AU - Nosho, Katsuhiko

AU - Shinomura, Yasuhisa

PY - 2014/12/4

Y1 - 2014/12/4

N2 - Background: Gene mutations in the pathway downstream of epidermal growth factor receptor (EGFR) are considered to induce resistance to anti-EGFR therapy in colorectal cancer (CRC). We recently reported that microRNA-31 (miR-31)-5p may regulate BRAF activation and play a role in the signaling pathway downstream of EGFR in CRC. Therefore, we hypothesized that miR-31-5p can be a useful biomarker for anti-EGFR therapy in CRC. Methods: We evaluated miR-31-5p expression and gene mutations [KRAS (codon 61 or 146), NRAS (codon 12, 13, or 61), and BRAF (V600E)] in the EGFR downstream pathway in 102 CRC patients harboring KRAS (codon 12 or 13) wild-type who were treated with anti-EGFR therapeutics. Progression-free survival (PFS) and overall survival (OS) were evaluated. Results: KRAS (codon 61 or 146), NRAS, and BRAF mutations were detected in 6.9, 6.9, and 5.9 % patients, respectively. Compared with CRCs with at least one mutation (n = 20), significantly better PFS (P = 0.0003) but insignificantly better OS were observed in CRCs harboring all wild-type genes (KRAS, NRAS, and BRAF). High miR-31-5p expression was identified in 11 % (n = 11) patients and was significantly associated with shorter PFS (P = 0.003). In CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS (P = 0.027). Conclusions: High miR-31-5p expression was associated with shorter PFS in patients with CRC treated with anti-EGFR therapeutics. Moreover, in CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS, suggesting that it may be a useful and additional prognostic biomarker for anti-EGFR therapy.

AB - Background: Gene mutations in the pathway downstream of epidermal growth factor receptor (EGFR) are considered to induce resistance to anti-EGFR therapy in colorectal cancer (CRC). We recently reported that microRNA-31 (miR-31)-5p may regulate BRAF activation and play a role in the signaling pathway downstream of EGFR in CRC. Therefore, we hypothesized that miR-31-5p can be a useful biomarker for anti-EGFR therapy in CRC. Methods: We evaluated miR-31-5p expression and gene mutations [KRAS (codon 61 or 146), NRAS (codon 12, 13, or 61), and BRAF (V600E)] in the EGFR downstream pathway in 102 CRC patients harboring KRAS (codon 12 or 13) wild-type who were treated with anti-EGFR therapeutics. Progression-free survival (PFS) and overall survival (OS) were evaluated. Results: KRAS (codon 61 or 146), NRAS, and BRAF mutations were detected in 6.9, 6.9, and 5.9 % patients, respectively. Compared with CRCs with at least one mutation (n = 20), significantly better PFS (P = 0.0003) but insignificantly better OS were observed in CRCs harboring all wild-type genes (KRAS, NRAS, and BRAF). High miR-31-5p expression was identified in 11 % (n = 11) patients and was significantly associated with shorter PFS (P = 0.003). In CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS (P = 0.027). Conclusions: High miR-31-5p expression was associated with shorter PFS in patients with CRC treated with anti-EGFR therapeutics. Moreover, in CRCs carrying all wild-type genes, high miR-31-5p was associated with shorter PFS, suggesting that it may be a useful and additional prognostic biomarker for anti-EGFR therapy.

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DO - 10.1245/s10434-014-4264-7

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JO - Annals of Surgical Oncology

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