Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun 130022, China.
Department of Obstetrics and Gynecology, The People's Hospital of LIAONING PROVINCE, Shenyang 110000, China.
Gynecol Oncol. 2022 Jul;166(1):138-147. doi: 10.1016/j.ygyno.2022.05.010. Epub 2022 May 18.
The role of kallikrein-related peptidase 5 (KLK5) has been studied in several diseases, including skin and ovarian cancers. However, its role in cervical cancer remains unclear, particularly in regulating the radiation resistance and growth of cervical cancer cells. Radiation resistance of cervical cancer is associated with local recurrence, distant metastasis, and reduced survival.
We first analyzed radiotherapy-naive samples and relevant clinical data from patients with cervical cancer who received radiotherapy without surgery or other antitumor treatment from 2014 to 2016. Subsequently, biopsied tissues, in vitro cells, and transplanted tumors in nude mice were investigated.
Gene sequencing and clinical data analysis showed that KLK5 overexpression was associated with a poor prognosis post-radiotherapy. In in vitro cell and tumor transplantation experiments, KLK5 overexpression significantly increased radiation resistance. However, downregulating KLK5 expression increased radiosensitivity.
Our results confirm that KLK5 is vital to the radioresistance of cervical cancer, and provide a new target and marker for the treatment of radioresistance in cervical cancer.
激肽释放酶相关肽酶 5(KLK5)在多种疾病中的作用已被研究,包括皮肤癌和卵巢癌。然而,其在宫颈癌中的作用仍不清楚,特别是在调节宫颈癌细胞的辐射抗性和生长方面。宫颈癌的辐射抗性与局部复发、远处转移和生存降低有关。
我们首先分析了 2014 年至 2016 年间接受过放疗但未接受手术或其他抗肿瘤治疗的宫颈癌患者的放疗前样本和相关临床数据。随后,对活检组织、体外细胞和裸鼠移植瘤进行了研究。
基因测序和临床数据分析表明,KLK5 过表达与放疗后预后不良有关。在体外细胞和肿瘤移植实验中,KLK5 过表达显著增加了辐射抗性。然而,下调 KLK5 表达可增加放射敏感性。
我们的研究结果证实 KLK5 对宫颈癌的辐射抗性至关重要,为宫颈癌的辐射抗性治疗提供了新的靶点和标志物。