Zhang Yan, Zhang Xing, Zhu Haixia, Liu Yang, Cao Jian, Li Dake, Ding Bo, Yan Wenjing, Jin Hua, Wang Shizhi
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, People's Republic of China.
Clinical Laboratory, Affiliated Tumor Hospital of Nantong University (Nantong Tumor Hospital), Nantong, People's Republic of China.
Cancer Manag Res. 2020 Jan 31;12:719-730. doi: 10.2147/CMAR.S231796. eCollection 2020.
Cervical cancer (CC) is one of the most common malignant tumors in women, and its treatment is often accompanied by high recurrence. We aimed to identify the long non-coding RNAs (lncRNAs) associated with CC recurrence.
We downloaded lncRNAs expression data of CC patients from The Cancer Genome Atlas (TCGA) dataset and used Cox regression models to analyze the lncRNAs relationship with CC recurrence. The significantly associated lncRNAs were utilized to construct a recurrence risk score (RRS) model. Bioinformatics analyses were used to assess the potential role of the critical lncRNAs in CC recurrence. The effect of critical lncRNAs on CC phenotype was determined by in vitro experiments.
Using Cox regression analysis, four lncRNAs, ie, HCG11, CASC15, LINC00189, and LINC00905, were markedly associated with worse recurrence-free survival (RFS) of CC, whereas three lncRNAs, including HULC, LINC00173, and MIR22HG, were the opposite. After constructing the RRS model, Kaplan-Meier analysis revealed that patients with high RRS had significantly increased risk of recurrence. Among the 20 types of tumors in the TCGA database which all had adjacent normal tissues, MIR22HG and HCG11were significantly downregulated in 18 and 10 types of tumors including CC, respectively. Increased MIR22HG was significantly relevant to decreased risks of recurrence among the subgroups of age at diagnosis < 45 (Hazard Ratio (HR) = 0.26), stage I/II (HR = 0.33), T stage I/II (HR = 0.30), chemotherapy (HR = 0.18), and molecular therapy (HR = 0.16). Functionally, elevated MIR22HG expression could suppress CC cell proliferation, migration and invasion.
MIR22HG has a fundamental role in CC recurrence and could be served as a potential prognostic biomarker.
宫颈癌（CC）是女性最常见的恶性肿瘤之一，其治疗常伴随着高复发率。我们旨在鉴定与CC复发相关的长链非编码RNA（lncRNA）。
我们从癌症基因组图谱（TCGA）数据集中下载了CC患者的lncRNA表达数据，并使用Cox回归模型分析lncRNA与CC复发的关系。利用显著相关的lncRNA构建复发风险评分（RRS）模型。采用生物信息学分析评估关键lncRNA在CC复发中的潜在作用。通过体外实验确定关键lncRNA对CC表型的影响。
通过Cox回归分析，发现四个lncRNA，即HCG11、CASC15、LINC00189和LINC00905，与CC较差的无复发生存期（RFS）显著相关，而包括HULC、LINC00173和MIR22HG在内的三个lncRNA则相反。构建RRS模型后，Kaplan-Meier分析显示高RRS患者的复发风险显著增加。在TCGA数据库中所有具有相邻正常组织的20种肿瘤类型中，MIR22HG和HCG11分别在包括CC在内的18种和10种肿瘤类型中显著下调。在诊断年龄<45岁（风险比（HR）=0.26）、I/II期（HR = 0.33）、T分期I/II期（HR = 0.30）、化疗（HR = 0.18）和分子治疗（HR = 0.16）的亚组中，MIR22HG升高与复发风险降低显著相关。在功能上，MIR22HG表达升高可抑制CC细胞的增殖、迁移和侵袭。
MIR22HG在CC复发中起重要作用，可作为潜在的预后生物标志物。
