Department of Infectious Disease, Shengjing Hospital of China Medical University, Shenyang 110004, People’s Republic of China.
Department of Pathology, Beijing Ditan Hospital, Capital Medical University, Chaoyang 100015, Beijing, People’s Republic of China.
Aging (Albany NY). 2023 Jul 26;15(14):7237-7257. doi: 10.18632/aging.204904.
Non-SMC condensin I complex subunit D2 (NCAPD2) is overexpressed in some malignant tumors. However, there are few studies on the function of NCAPD2 in pan-cancer. We used the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), and UALCAN to analyze NCAPD2 expression and promoter methylation levels in 33 tumors and normal samples. We performed immunohistochemistry (IHC) on liver cancer and corresponding normal tissues to examine NCAPD2 protein expression in LIHC. Kaplan-Meier survival and univariate regression analyses were performed to explore the pan-cancer clinical significance of NCAPD2. Moreover, correlative analysis between NCAPD2 expression and clinical characteristics, immune cell infiltration, immune checkpoints, immune regulators, tumor mutation burden (TMB), microsatellite instability (MSI), ribonucleic acid (RNA) methylation regulators, and drug sensitivity was conducted using data from TCGA. We also investigated the effects of NCAPD2 expression on immunotherapy efficacy and prognosis. Gene set enrichment analysis (GSEA) was conducted using NCAPD2. Bioinformatic analysis showed that NCAPD2 was overexpressed in most tumors and correlated with the clinical characteristics of some cancers. IHC results demonstrated that NCAPD2 protein expression was higher in LIHC than in normal liver. NCAPD2 expression was linked with T stage, clinical stage, and histologic grade in LIHC. Overexpression of NCAPD2 resulted in poor overall survival, and disease-specific survival in adrenocortical carcinoma, kidney renal papillary cell carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, lung adenocarcinoma, mesothelioma, pancreatic adenocarcinoma, sarcoma, skin cutaneous melanoma, and uterine corpus endometrial carcinoma. NCAPD2 was considered an independent biomarker by Cox regression in LIHC. The time ROC curve demonstrated that the survival rate of 1-, 3-, and 5-year OS and DSS in LIHC was above 0.6. The expression of NCAPD2 was significantly correlated with immune cell infiltration, immune checkpoints, TMB, MSI, and RNA methylation regulators in several tumors. NCAPD2 had a high predictive value for immunotherapy efficiency in certain tumors. In our study, drugs sensitive to NCAPD2 protein were screened by sensitivity analysis. GSEA analysis showed that NCAPD2 mainly participated in the G2M checkpoint, mitotic spindle, and KRAS-signaling. NCAPD2 may act as a prognostic molecular marker in most cancers.
非 SMC 凝聚素 I 复合物亚基 D2（NCAPD2）在一些恶性肿瘤中过表达。然而，关于 NCAPD2 在泛癌中的功能研究较少。我们使用癌症基因组图谱（TCGA）、基因型组织表达（GTEx）、人类蛋白质图谱（HPA）和 UALCAN 分析了 33 种肿瘤和正常样本中 NCAPD2 的表达和启动子甲基化水平。我们对肝癌和相应的正常组织进行了免疫组织化学（IHC）检测，以研究 LIHC 中 NCAPD2 蛋白的表达。进行 Kaplan-Meier 生存和单因素回归分析以探讨 NCAPD2 在泛癌中的临床意义。此外，还使用 TCGA 中的数据进行了 NCAPD2 表达与临床特征、免疫细胞浸润、免疫检查点、免疫调节剂、肿瘤突变负荷（TMB）、微卫星不稳定性（MSI）、核糖核酸（RNA）甲基化调节剂和药物敏感性之间的相关性分析。我们还研究了 NCAPD2 表达对免疫治疗疗效和预后的影响。使用 NCAPD2 进行基因集富集分析（GSEA）。生物信息学分析表明，NCAPD2 在大多数肿瘤中过表达，并与某些癌症的临床特征相关。IHC 结果表明，LIHC 中 NCAPD2 蛋白表达高于正常肝脏。NCAPD2 表达与 LIHC 中的 T 分期、临床分期和组织学分级相关。NCAPD2 过表达导致肾上腺皮质癌、肾肾乳头细胞癌、脑低级别胶质瘤、肝癌、肺腺癌、间皮瘤、胰腺腺癌、肉瘤、皮肤黑色素瘤和子宫体子宫内膜癌的总生存期和疾病特异性生存期较差。在 LIHC 中，Cox 回归认为 NCAPD2 是一个独立的生物标志物。时间 ROC 曲线表明，LIHC 中 1 年、3 年和 5 年 OS 和 DSS 的生存率均高于 0.6。在几种肿瘤中，NCAPD2 的表达与免疫细胞浸润、免疫检查点、TMB、MSI 和 RNA 甲基化调节剂显著相关。NCAPD2 对某些肿瘤的免疫治疗效率具有较高的预测价值。在我们的研究中，通过敏感性分析筛选了对 NCAPD2 蛋白敏感的药物。GSEA 分析表明，NCAPD2 主要参与 G2M 检查点、有丝分裂纺锤体和 KRAS 信号通路。NCAPD2 可能在大多数癌症中作为一种预后分子标志物。
