Ouyang Wen, Ren Linlin, Liu Guohong, Chi Xiaosa, Wei Hongyun
The Second Clinical Medical College, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Department of Gastroenterology, Affiliated hospital of Qingdao University, Qingdao, Shandong, China.
PeerJ. 2019 Apr 2;7:e6683. doi: 10.7717/peerj.6683. eCollection 2019.
LncRNA MIR4435-2HG is observed in a variety of cancers, while its role in colorectal cancer is unknown. We aimed to demonstrate the relationship between MIR4435-2HG and colorectal cancer based on The Cancer Genome Atlas (TCGA) database.
Patients with colorectal cancer were collected from TCGA. We compared the expression of MIR4435-2HG in colorectal cancer and normal tissues with Wilcoxon rank sum test, and logistic regression was used to evaluate the relationship between MIR4435-2HG and clinicopathological characters. Moreover, Kaplan-Meier and Cox regression was performed to evaluate the correlation between MIR4435-2HG and survival rate. Gene set enrichment analysis (GSEA) was also conducted to annotate biological function of MIR4435-2HG.
MIR4435-2HG level was elevated in colorectal cancer tissues. Increased level of MIR4435-2HG was significantly correlated with TNM stage (OR = 1.66 for T1/T2 vs. T3/T4; OR = 1.68 for N0 vs. N1/N2), stage (OR = 1.66 for stage 1/2 vs. stage 3/4), and carcinoembryonic antigen level before treatment (OR = 1.70 for <5 vs. ≥5) (all -value <0.05). High MIR4435-2HG expression had a poorer progression-free survival ( = 0.048), and overall survival (OS) ( = 0.028), which were validated in the GSE92921 and GSE29621 datasets. MIR4435-2HG expression ( = 0.040, HR = 1.955 (95% CI [1.031-3.710])) was independently correlated with OS. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway, the cell surface interactions at the vascular wall, and integrin cell surface interactions were differentially enriched in MIR4435-2HG high expression phenotype.
Increased MIR4435-2HG might be a potential biomarker for the diagnosis and prognosis of colorectal cancer. Moreover, MIR4435-2HG might participate in the development of colorectal cancer via the P38/MAPK and VEGF pathway.
长链非编码RNA MIR4435-2HG在多种癌症中均有发现，但其在结直肠癌中的作用尚不清楚。我们旨在基于癌症基因组图谱（TCGA）数据库阐明MIR4435-2HG与结直肠癌之间的关系。
从TCGA收集结直肠癌患者。我们采用Wilcoxon秩和检验比较结直肠癌组织与正常组织中MIR4435-2HG的表达，并使用逻辑回归评估MIR4435-2HG与临床病理特征之间的关系。此外，进行Kaplan-Meier分析和Cox回归以评估MIR4435-2HG与生存率之间的相关性。还进行了基因集富集分析（GSEA）以注释MIR4435-2HG的生物学功能。
结直肠癌组织中MIR4435-2HG水平升高。MIR4435-2HG水平升高与TNM分期（T1/T2与T3/T4相比，OR = 1.66；N0与N1/N2相比，OR = 1.68）、分期（1/2期与3/4期相比，OR = 1.66）以及治疗前癌胚抗原水平（<5与≥5相比，OR = 1.70）均显著相关（所有P值<0.05）。MIR4435-2HG高表达的无进展生存期（P = 0.048）和总生存期（OS）（P = 0.028）较差，这在GSE92921和GSE29621数据集中得到验证。MIR4435-2HG表达（P = 0.04, HR = 1.955（95%CI[1.031 - 3.710]））与OS独立相关。GSEA表明，P38/MAPK通路、VEGF通路、细胞黏附分子cams、NOD样受体信号通路、血管壁处的细胞表面相互作用以及整合素细胞表面相互作用在MIR4435-2HG高表达表型中差异富集。
MIR4435-2HG水平升高可能是结直肠癌诊断和预后的潜在生物标志物。此外，MIR4435-2HG可能通过P38/MAPK和VEGF通路参与结直肠癌的发生发展。
