Department of Obstetrics and Gynaecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Mol Med Rep. 2018 Dec;18(6):5173-5181. doi: 10.3892/mmr.2018.9550. Epub 2018 Oct 10.
Epithelial ovarian cancer (EOC) is one of the leading causes of cancer‑associated mortality in women. At present, the overall 5‑year survival rate of patients with EOC remains poor despite advancements in diagnosis and treatment. Long non‑coding RNAs (lncRNAs) have attracted increasing attention in recent years for their extensive roles in tumorigenesis and cancer development. The lncRNA cancer susceptibility candidate 2 (CASC2) was originally identified as a downregulated gene in endometrial cancer, and subsequent studies revealed that CASC2 was able to act as a tumor suppressor gene in various types of cancer. The present study is the first, to the best of the authors' knowledge, to identify the clinical significance and potential role of CASC2 in EOC. The results demonstrated that CASC2 was downregulated in EOC cell lines and tissues. Analysis of association between clinicopathological features and CASC2 expression levels suggested that low CASC2 expression is associated with the serous histological subtype (P<0.001), lymph node metastasis (P=0.038), poor histological grade (P<0.001) and large tumor size (P=0.001) in EOC. Furthermore, low CASC2 expression predicted poor overall survival (P<0.001) and progression‑free survival (P<0.001). Functional assays, including Cell Counting kit‑8 assays, colony formation assays, and Transwell and Matrigel assays, confirmed that silencing of CASC2 promoted the proliferation, migration and invasion of EOC cells; whereas, ectopic overexpression of CASC2 suppressed the proliferation, migration and invasion of EOC cells. In addition, in the analysis of the risk factors for poor prognosis, low CASC2 expression was identified as an independent risk factor for reduced overall survival [hazard ratio (HR)=0.417; 95% confidence interval (CI)=0.251‑0.693; P=0.001] and progression‑free survival (HR=0.426; 95% CI=0.260‑0.699; P=0.001) in patients with EOC. In conclusion, CASC2 is downregulated in EOC, and it may suppress EOC progression and is an independent risk factor for poor prognosis. CASC2 may be a promising prognostic marker and therapeutic target in EOC.
上皮性卵巢癌 (EOC) 是导致女性癌症相关死亡的主要原因之一。尽管在诊断和治疗方面取得了进展，但目前 EOC 患者的总体 5 年生存率仍然较差。近年来，长链非编码 RNA (lncRNA) 因其在肿瘤发生和癌症发展中的广泛作用而引起了越来越多的关注。lncRNA 癌症易感性候选基因 2 (CASC2) 最初被鉴定为子宫内膜癌中下调的基因，随后的研究表明 CASC2 能够作为各种类型癌症的肿瘤抑制基因发挥作用。本研究首次确定了 CASC2 在 EOC 中的临床意义和潜在作用。结果表明，CASC2 在 EOC 细胞系和组织中表达下调。对 CASC2 表达水平与临床病理特征之间的关联进行分析表明，CASC2 低表达与浆液性组织学亚型（P<0.001）、淋巴结转移（P=0.038）、组织学分级差（P<0.001）和肿瘤体积大（P=0.001）相关。此外，CASC2 低表达预示着总体生存（P<0.001）和无进展生存（P<0.001）不良。细胞计数试剂盒-8 测定、集落形成测定、Transwell 和 Matrigel 测定等功能测定证实，沉默 CASC2 促进了 EOC 细胞的增殖、迁移和侵袭；而 CASC2 的异位过表达抑制了 EOC 细胞的增殖、迁移和侵袭。此外，在对不良预后危险因素的分析中，CASC2 低表达被确定为总体生存降低的独立危险因素[风险比 (HR)=0.417；95%置信区间 (CI)=0.251-0.693；P=0.001]和无进展生存 (HR=0.426；95%CI=0.260-0.699；P=0.001)。综上所述，CASC2 在 EOC 中表达下调，可能抑制 EOC 进展，是不良预后的独立危险因素。CASC2 可能是 EOC 有前途的预后标志物和治疗靶点。
