Guo Wei, Huai Qilin, Zhang Guochao, Guo Lei, Song Peng, Xue Xuemin, Tan Fengwei, Xue Qi, Gao Shugeng, He Jie
Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Graduate School, Zunyi Medical University, Zunyi, China.
Front Oncol. 2021 Jan 25;10:598437. doi: 10.3389/fonc.2020.598437. eCollection 2020.
Lung adenocarcinoma (LUAD), as the most common histological subtype of lung cancer, is a high-grade malignancy and a leading cause of cancer-related death globally. Identification of biomarkers with prognostic value is of great significance for the diagnosis and treatment of LUAD. Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an RNA-binding protein "reader" of N6-methyladenosine (mA) methylation, and is related to the progression of various cancers; however, its role in LUAD is unclear. The aims of this study aims were to study the expression and prognostic value of HNRNPC in LUAD.
The Oncomine database and gene expression profiling interactive analysis (GEPIA) were used for preliminary exploration of HNRNPC expression and prognostic value in LUAD. LUAD cases from The Cancer Genome Atlas (TCGA) (n = 416) and the Kaplan-Meier plotter database (n = 720) were extracted to study the differential expression and prognostic value of HNRNPC. HNRNPC expression in the National Cancer Center of China (NCC) cohort was analyzed by immunohistochemical staining, and the relationship between HNRNPC expression and survival rate evaluated using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. Several pathways that were significantly enriched in the HNRNPC high expression group were identified by Gene Set Enrichment Analysis (GSEA).
Five data sets from the Oncomine and GEPIA databases all supported that HNRNPC expression is significantly higher in LUAD than in normal lung tissue. In TCGA cohort, HNRNPC was highly expressed in LUAD tissues and significantly related to age, sex, smoking history, ethnicity, lymph node metastasis, and TNM staging ( < 0.001). High HNRNPC expression was significantly correlated with poor prognosis in the three cohorts (NCC, TCGA, and K-M plotter) ( < 0.05). Multivariate Cox regression analysis showed that HNRNPC expression was an independent prognostic factor in both TCGA and NCC cohorts ( < 0.05). Further, 10 significantly enriched pathways were identified from TCGA data and 118 lung cancer cell lines in CCLE, respectively.
High HNRNPC expression is significantly related to poor overall survival in patients with LUAD, suggesting that HNRNPC may be a cancer-promoting factor and a potential prognostic biomarker in LUAD.
肺腺癌（LUAD）是肺癌最常见的组织学亚型，是一种高度恶性肿瘤，也是全球癌症相关死亡的主要原因。鉴定具有预后价值的生物标志物对LUAD的诊断和治疗具有重要意义。异质性核糖核蛋白C（HNRNPC）是N6-甲基腺苷（mA）甲基化的一种RNA结合蛋白“读取器”，与多种癌症的进展相关；然而，其在LUAD中的作用尚不清楚。本研究的目的是研究HNRNPC在LUAD中的表达及预后价值。
利用Oncomine数据库和基因表达谱交互式分析（GEPIA）对HNRNPC在LUAD中的表达及预后价值进行初步探索。提取来自癌症基因组图谱（TCGA）（n = 416）和Kaplan-Meier绘图仪数据库（n = 720）的LUAD病例，以研究HNRNPC的差异表达和预后价值。通过免疫组织化学染色分析中国国家癌症中心（NCC）队列中HNRNPC的表达，并使用Kaplan-Meier方法和对数秩检验评估HNRNPC表达与生存率之间的关系。采用单因素和多因素Cox回归分析来确定独立的预后因素。通过基因集富集分析（GSEA）确定了在HNRNPC高表达组中显著富集的几条通路。
来自Oncomine和GEPIA数据库的5个数据集均支持HNRNPC在LUAD中的表达显著高于正常肺组织。在TCGA队列中，HNRNPC在LUAD组织中高表达，且与年龄、性别、吸烟史、种族、淋巴结转移和TNM分期显著相关（<0.001）。在三个队列（NCC、TCGA和K-M绘图仪）中，HNRNPC高表达均与不良预后显著相关（<0.05）。多因素Cox回归分析表明，HNRNPC表达在TCGA和NCC队列中均为独立的预后因素（<0.05）。此外，分别从TCGA数据和CCLE中的118个肺癌细胞系中鉴定出10条显著富集的通路。
HNRNPC高表达与LUAD患者的总生存期差显著相关，提示HNRNPC可能是LUAD中的促癌因子和潜在的预后生物标志物。
