NCAPH 在子宫内膜癌中上调，并与不良的临床病理特征相关。

NCAPH is upregulated in endometrial cancer and associated with poor clinicopathologic characteristics.

机构信息

Department of Gynecology and Obstetrics, Zaozhuang Shizhong District Maternal and Child Health Hospital, Zaozhuang, Shandong, China.

Department of Ultrasound, Zaozhuang Shizhong District Maternal and Child Health Hospital, Zaozhuang, Shandong, China.

出版信息

Ann Hum Genet. 2020 Nov;84(6):437-446. doi: 10.1111/ahg.12398. Epub 2020 Jul 6.

DOI:10.1111/ahg.12398

PMID:32628282

Abstract

BACKGROUND

Recently, NCAPH (non-SMC condensin I complex subunit H), a regulatory subunit of the condensin complex, has captured our attention in various cancer studies. However, the function of NCAPH in endometrial cancer (EC) remains unclear. Our study aims to investigate the role of NCAPH in EC.

METHODS

The expression of NCAPH in EC tissues and normal tissues was predicted by The Cancer Genome Atlas (TCGA). The Kaplan-Meier analysis was performed to evaluate the impact of NCAPH expression on EC patients' survival. Logistic regression was used to study the correlation of NCAPH expression with clinicopathologic characteristics. Molecular mechanisms behind NCAPH in EC were evaluated by Gene Set Enrichment Analysis, genetic mutations, copy number variation, and DNA methylation level.

RESULTS

NCAPH was significantly upregulated in EC (p = 1e-24), and its expression level was significantly related to the more advanced International Federation of Gynecology & Obstetrics (FIGO) stage (stage IV vs. stage I: odd ratio.[OR] = 3.7), higher grade (poor vs. well & moderate: OR = 5.3), serous histology subtype (SEA vs. EEA: OR = 8.5), myometrial invasion (≥50 vs. < 50 invasion: OR = 1.8), metastasis (vs. no metastasis: OR = 2.5), and with-tumor status (vs. free of tumor: OR = 2.3) (all p were less than .05). The Gene Set Enrichment Analysis method indicated that MITOTIC_SPINDLE, G2M_CHECKPOINT, MYC_TARGETS_V1, E2F_TARGETS, MYC_TARGETS_V2, and MTORC1_SIGNALING were involved in the upregulated NCAPH group. NCAPH hypomethylation, amplified copy number variations and genetic mutations; all played a contributive role in NCAPH upregulation.

CONCLUSIONS

These results reveal NCAPH functions as oncogene and promote the development of EC.

摘要

背景

最近，NCAPH（非 SMC 凝聚素 I 复合物亚基 H）作为凝聚素复合物的调节亚基，在各种癌症研究中引起了我们的关注。然而，NCAPH 在子宫内膜癌（EC）中的作用尚不清楚。我们的研究旨在探讨 NCAPH 在 EC 中的作用。

方法

通过癌症基因组图谱（TCGA）预测 NCAPH 在 EC 组织和正常组织中的表达。通过 Kaplan-Meier 分析评估 NCAPH 表达对 EC 患者生存的影响。采用逻辑回归研究 NCAPH 表达与临床病理特征的相关性。通过基因集富集分析、遗传突变、拷贝数变异和 DNA 甲基化水平评估 NCAPH 在 EC 中的分子机制。

结果

NCAPH 在 EC 中显著上调（p=1e-24），其表达水平与更晚期的国际妇产科联合会（FIGO）分期（IV 期与 I 期：比值比[OR]=3.7）、更高的分级（差与中、好：OR=5.3）、浆液组织学亚型（SEA 与 EEA：OR=8.5）、肌层浸润（≥50 与<50 浸润：OR=1.8）、转移（与无转移：OR=2.5）和带瘤状态（与无瘤：OR=2.3）显著相关（所有 p 值均小于 0.05）。基因集富集分析方法表明，MITOTIC_SPINDLE、G2M_CHECKPOINT、MYC_TARGETS_V1、E2F_TARGETS、MYC_TARGETS_V2 和 MTORC1_SIGNALING 参与了上调的 NCAPH 组。NCAPH 低甲基化、扩增的拷贝数变异和遗传突变均在 NCAPH 上调中发挥了作用。