Shimomura Masahiro, Fukuda Takeshi, Awazu Yuichiro, Nanno Shigenori, Inoue Yuta, Matsubara Hiroaki, Yamauchi Makoto, Yasui Tomoyo, Sumi Toshiyuki
Department of Obstetrics and Gynecology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
Oncol Lett. 2021 Feb;21(2):150. doi: 10.3892/ol.2020.12411. Epub 2020 Dec 24.
The standard care for patients with locally advanced cervical cancer is concurrent chemoradiotherapy. Successful neoadjuvant chemotherapy (NAC) can reduce tumor size and enable patients to be eligible for a hysterectomy, which can improve their prognosis. Selecting the right candidate for NAC is important since NAC failure results in switching to radiation therapy and can lead to a worse prognosis due to a delay in the initiation of the core therapy. Therefore, the identification of biomarkers that can predict the effect of NAC is essential. Previous reports have suggested a relationship between protein arginine methyltransferase (PRMT1) and chemoresistance in several types of cancer. PRMT1 has been demonstrated to methylate apoptosis signal-regulated kinase 1 and to inhibit its activity, thereby contributing to chemoresistance. The present study investigated the association between PRMT1 expression and the efficacy of NAC in locally advanced cervical cancer. Data from 53 patients with locally advanced uterine cervical cancer who were classified into two groups based on effective (n=28) and ineffective (n=25) responses to NAC treatment were evaluated. PRMT1 expression was investigated by immunohistochemistry and scored using a weighted scoring system. Additionally, the present study investigated the effect of RNA interference-mediated downregulation of PRMT1 on the sensitivity of cervical cancer cells to cisplatin . The results demonstrated that the NAC effective group had significantly lower weighted PRMT1 scores than the NAC ineffective group (P=0.030). In addition, lower tumor expression levels of PRMT1 were significantly associated with increased sensitivity to NAC (P=0.033). Furthermore, downregulation of PRMT1 expression in cervical cancer cells markedly improved their sensitivity to cisplatin . The present study suggested that PRMT1 expression has potential as a predictive marker of the efficacy of NAC in patients with locally advanced cervical cancer. This finding can contribute to improvements in the prognosis of these patients.
局部晚期宫颈癌患者的标准治疗是同步放化疗。成功的新辅助化疗(NAC)可缩小肿瘤大小,使患者有资格接受子宫切除术,从而改善其预后。选择合适的NAC候选者很重要,因为NAC失败会导致转而接受放疗,并可能因核心治疗开始延迟而导致预后更差。因此,识别可预测NAC疗效的生物标志物至关重要。既往报道提示蛋白精氨酸甲基转移酶(PRMT1)与几种癌症的化疗耐药有关。已证实PRMT1可使凋亡信号调节激酶1甲基化并抑制其活性,从而导致化疗耐药。本研究调查了PRMT1表达与局部晚期宫颈癌NAC疗效之间的关联。评估了53例局部晚期子宫颈癌患者的数据,这些患者根据对NAC治疗的有效(n=28)和无效(n=25)反应分为两组。通过免疫组织化学研究PRMT1表达,并使用加权评分系统进行评分。此外,本研究还调查了RNA干扰介导的PRMT1下调对宫颈癌细胞对顺铂敏感性的影响。结果表明,NAC有效组的PRMT1加权评分显著低于NAC无效组(P=0.030)。此外,PRMT1的肿瘤表达水平较低与对NAC的敏感性增加显著相关(P=0.033)。此外,宫颈癌细胞中PRMT1表达的下调显著提高了它们对顺铂的敏感性。本研究提示,PRMT1表达有可能作为局部晚期宫颈癌患者NAC疗效的预测标志物。这一发现有助于改善这些患者的预后。