PRMT1 expression predicts sensitivity to platinum‑based chemotherapy in patients with ovarian serous carcinoma

Matsubara,Hiroaki; Fukuda,Takeshi; Awazu,Yuichiro; Nanno,Shigenori; Shimomura,Masahiro; Inoue,Yuta; Yamauchi,Makoto; Yasui,Tomoyo; Sumi,Toshiyuki

doi:10.3892/ol.2020.12423

PRMT1 expression predicts sensitivity to platinum‑based chemotherapy in patients with ovarian serous carcinoma

Authors:
- Hiroaki Matsubara
- Takeshi Fukuda
- Yuichiro Awazu
- Shigenori Nanno
- Masahiro Shimomura
- Yuta Inoue
- Makoto Yamauchi
- Tomoyo Yasui
- Toshiyuki Sumi
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Affiliations: Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka 545‑8585, Japan
Published online on: December 31, 2020 https://doi.org/10.3892/ol.2020.12423
Article Number: 162

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Abstract

Patients with ovarian serous carcinoma are generally diagnosed at an advanced disease stage. The standard treatment for these patients is maximal debulking surgery followed by platinum‑taxane combination chemotherapy. Despite initially responding well, more than half of patients become refractory to first‑line chemotherapy. Upregulation of protein arginine methyltransferase 1 (PRMT1) expression has been demonstrated to methylate apoptosis signal‑regulated kinase 1 and inhibit its activity, thereby contributing to chemoresistance. The present study investigated the association between PRMT1 expression and sensitivity to platinum‑based chemotherapy in 51 patients with ovarian serous carcinoma (International Federation of Gynecology and Obstetrics stages III and IV), and the effect of RNA interference‑mediated downregulation of PRMT1 on the sensitivity of ovarian cancer cells to cisplatin and carboplatin in vitro. Immunohistochemistry of tumor specimens was used to compare the expression levels of PRMT1, a Cell Counting Kit‑8 assay and small interfering RNA transfection were performed for chemosensitivity assays, and reverse transcription‑quantitative PCR was used to examine PRMT1 mRNA expression. Patients were divided into platinum‑sensitive (n=26) and platinum‑resistant (n=25) groups. PRMT1 expression was significantly lower in the platinum‑sensitive group than in the platinum‑resistant group (P=0.019). When patients were categorized according to PRMT1 expression, those in the low PRMT1 expression group were more sensitive to platinum‑based chemotherapy than those in the high PRMT1 expression group (P=0.01). Additionally, in vitro experiments revealed that suppression of PRMT1 expression by siRNA significantly increased the sensitivity of human ovarian serous carcinoma cells to cisplatin and carboplatin (P<0.05). In conclusion, PRMT1 expression could predict sensitivity to platinum‑based chemotherapy in patients with ovarian serous carcinoma.

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