Zhang Peijin, Lin Yang, Liu Yaqiong
Department of Gynecology, Tianjin Central Hospital of Gynecology Obstetrics, Tianjin 300100, P.R. China.
Department of Gynecology and Obstetrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China.
Exp Ther Med. 2021 Jul;22(1):776. doi: 10.3892/etm.2021.10208. Epub 2021 May 18.
Ca-activated Cl channel A2 (CLCA2), a tumor suppressor, is associated with the development of several cancers. However, little is known about CLCA2 in human cervical cancer. Therefore, the aim of the present study was to investigate the effects of CLCA2 on cervical cancer. Reverse transcription-quantitative (RT-q)PCR was used to examine the mRNA expression levels of CLCA2 in eight pairs of cervical cancer tissues. Immunohistochemistry was used to investigate CLCA2 protein expression in 144 archived cervical cancer specimens. The association of the CLCA2 with clinicopathological parameters was statistically evaluated. Cell proliferation and invasion capability were examined by MTT and Transwell assays, respectively. RT-qPCR analysis revealed that CLCA2 expression was decreased in cervical cancer compared with that in adjacent normal tissues. The expression levels of CLCA2 in patients were correlated with tumor stage (P=0.028), tumor size (P=0.009), and human papillomavirus (HPV) infection status (P=0.041). In addition, CLCA2 upregulation was associated with longer overall and recurrence-free survival time after surgery (P=0.016 and P=0.009, respectively). Multivariate Cox regression analysis demonstrated that CLCA2 expression had a predictive value for overall survival of patients with cervical cancer (P=0.017 and P=0.025, respectively). Knockdown of CLCA2 by small interfering RNA suppressed tumor cell proliferation and migration. Mechanistically, CLCA2 was involved in Wnt/β-catenin signaling. In conclusion, the results of the present study demonstrated that CLCA2 suppressed the proliferation, migration and invasion of cervical cancer cells, and that CLCA2 may be a potential therapeutic target of cervical cancer.
钙激活氯离子通道A2（CLCA2）作为一种肿瘤抑制因子，与多种癌症的发生发展相关。然而，关于CLCA2在人类宫颈癌中的作用却知之甚少。因此，本研究旨在探讨CLCA2对宫颈癌的影响。采用逆转录定量（RT-q）PCR检测8对宫颈癌组织中CLCA2的mRNA表达水平。运用免疫组织化学方法研究144例存档宫颈癌标本中CLCA2蛋白的表达情况。对CLCA2与临床病理参数之间的相关性进行统计学评估。分别通过MTT法和Transwell实验检测细胞增殖和侵袭能力。RT-qPCR分析显示，与相邻正常组织相比，宫颈癌组织中CLCA2表达降低。患者体内CLCA2的表达水平与肿瘤分期（P=0.028）、肿瘤大小（P=0.009）以及人乳头瘤病毒（HPV）感染状态（P=0.041）相关。此外，CLCA2的上调与术后更长的总生存期和无复发生存期相关（分别为P=0.016和P=0.009）。多因素Cox回归分析表明，CLCA2表达对宫颈癌患者的总生存期具有预测价值（分别为P=0.017和P=0.025）。通过小干扰RNA敲低CLCA2可抑制肿瘤细胞的增殖和迁移。机制上，CLCA2参与Wnt/β-连环蛋白信号通路。总之，本研究结果表明，CLCA2可抑制宫颈癌细胞的增殖、迁移和侵袭，并且CLCA2可能是宫颈癌潜在的治疗靶点。
