Plasma exosomal microRNA‑125b as a monitoring biomarker of resistance to mFOLFOX6‑based chemotherapy in advanced and recurrent colorectal cancer patients

  • Authors:
    • Takahiro Yagi
    • Hisae Iinuma
    • Tamuro Hayama
    • Keiji Matsuda
    • Keijirou Nozawa
    • Mitsuo Tsukamoto
    • Ryu Shimada
    • Takuya Akahane
    • Takeshi Tsuchiya
    • Tsuyoshi Ozawa
    • Yojiro Hashiguchi
  • View Affiliations

  • Published online on: August 14, 2019     https://doi.org/10.3892/mco.2019.1911
  • Pages: 416-424
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Abstract

Liquid biomarkers for the early detection of resistance to chemotherapy are important for improving prognosis. This study investigated the usefulness of plasma exosomal microRNA‑125b (ex‑miRNA‑125b) for the early detection of resistance to modified fluorouracil, leucovorin and oxaliplatin (mFOLFOX6)‑based first‑line chemotherapy in patients with advanced or recurrent (advanced/recurrent) colorectal cancer (CRC). First, ex‑miRNAs associated with resistance to mFOLFOX6‑based chemotherapy were profiled via miRNA microarray analysis. In this analysis, ex‑miR‑125b exhibited the greatest upregulation in patients with progressive disease (PD) compared with the findings for patients with stable disease (SD) and healthy controls. Next, another 55 patients with advanced/recurrent CRC who received mFOLFOX6‑based first‑line chemotherapy underwent a validation study of ex‑miR‑125b. Blood samples were collected before and during treatment until tumor progression. Ex‑miRNA levels were measured via TaqMan microRNA assays. Patients with CRC had significantly higher ex‑miR‑125b levels than healthy controls. In patients with partial responses, ex‑miR‑125b levels at the Response Evaluation Criteria in Solid Tumors (RECIST) judgment point were significantly lower than those measured before treatment. In patients with SD, ex‑miR‑125b levels did not differ before and during treatment. In patients with PD, ex‑miR‑125b levels at the RECIST judgment point were significantly higher than those measured before treatment. These changes in ex‑miR‑125b levels were significantly different between groups even 1 month after the initiation of chemotherapy. Progression‑free survival (PFS) was significantly worse in patients with high baseline ex‑miR‑125b levels than in those with low levels. In the Cox analysis, baseline ex‑miR‑125b levels and KRAS mutation were indicated to be independent prognostic factors for PFS. The present results suggest that plasma ex‑miR‑125b levels may be useful for the early detection of resistance to mFOLFOX6‑based first‑line chemotherapy. Furthermore, ex‑miR‑125b before chemotherapy is a predictive biomarker for PFS in patients with advanced/recurrent CRC.

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October 2019
Volume 11 Issue 4

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Copy and paste a formatted citation
APA
Yagi, T., Iinuma, H., Hayama, T., Matsuda, K., Nozawa, K., Tsukamoto, M. ... Hashiguchi, Y. (2019). Plasma exosomal microRNA‑125b as a monitoring biomarker of resistance to mFOLFOX6‑based chemotherapy in advanced and recurrent colorectal cancer patients. Molecular and Clinical Oncology, 11, 416-424. https://doi.org/10.3892/mco.2019.1911
MLA
Yagi, T., Iinuma, H., Hayama, T., Matsuda, K., Nozawa, K., Tsukamoto, M., Shimada, R., Akahane, T., Tsuchiya, T., Ozawa, T., Hashiguchi, Y."Plasma exosomal microRNA‑125b as a monitoring biomarker of resistance to mFOLFOX6‑based chemotherapy in advanced and recurrent colorectal cancer patients". Molecular and Clinical Oncology 11.4 (2019): 416-424.
Chicago
Yagi, T., Iinuma, H., Hayama, T., Matsuda, K., Nozawa, K., Tsukamoto, M., Shimada, R., Akahane, T., Tsuchiya, T., Ozawa, T., Hashiguchi, Y."Plasma exosomal microRNA‑125b as a monitoring biomarker of resistance to mFOLFOX6‑based chemotherapy in advanced and recurrent colorectal cancer patients". Molecular and Clinical Oncology 11, no. 4 (2019): 416-424. https://doi.org/10.3892/mco.2019.1911