Department of General Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi.
Department of Radiation Oncology and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan.
Ann Clin Lab Sci. 2020 Nov;50(6):717-725.
Sine oculis homeobox homolog 2 (Six2), a developmental transcription factor, is known to be correlated with the development and prognosis of various cancers. In this study, we explored the prognostic value of Six2 in colon adenocarcinoma (COAD).
Wilcoxon signed-rank test and logistic regression were applied to identify relationship between clinical features and Six2 expression. The effect of Six2 expression and clinical features on the survival of COAD patients was explored using Kaplan-Meier and Cox regression analyses. Gene Set Enrichment Analysis (GSEA) was performed utilizing TCGA dataset.
Compared to adjacent normal tissues, Six2 was highly expressed in COAD. Overexpression of Six2 in COAD was significantly associated with M classification (OR=2.557, positive vs. negative), N classification (OR=2.636, N2 vs. N0), and stage (OR=1.864, III vs. I) (all -values<0.05). Patients with higher Six2 expression had significantly poor overall survival (OS, =0.003). The univariate analysis showed that high expression of Six2 was significantly correlated with a poor OS (HR=1.135, 95%Cl 1.038-1.241; =0.005). The multivariate analysis demonstrated that Six2 was an independent predictor of OS (HR=1.107, 95%Cl 1.007-1.216; =0.036). According to GSEA, differentially enriched pathways in the Six2 high expression phenotype, included the TGF- β and Wnt signaling pathway.
Six2 may be a valuable biomarker and potential therapeutic target for the treatment of COAD.
sine oculis homeobox homolog 2（Six2）作为一种发育转录因子，已知与多种癌症的发生和预后相关。本研究旨在探讨 Six2 在结肠腺癌（COAD）中的预后价值。
采用 Wilcoxon 符号秩检验和逻辑回归分析鉴定临床特征与 Six2 表达之间的关系。采用 Kaplan-Meier 和 Cox 回归分析探讨 Six2 表达和临床特征对 COAD 患者生存的影响。利用 TCGA 数据集进行基因集富集分析（GSEA）。
与相邻正常组织相比，Six2 在 COAD 中高表达。COAD 中 Six2 的过表达与 M 分类（OR=2.557，阳性 vs. 阴性）、N 分类（OR=2.636，N2 vs. N0）和分期（OR=1.864，III vs. I）显著相关（所有 P 值均<0.05）。Six2 表达较高的患者总生存期（OS）明显较差（P=0.003）。单因素分析显示，Six2 高表达与 OS 不良显著相关（HR=1.135，95%Cl 1.038-1.241；P=0.005）。多因素分析表明，Six2 是 OS 的独立预测因子（HR=1.107，95%Cl 1.007-1.216；P=0.036）。根据 GSEA，Six2 高表达表型中差异富集的途径包括 TGF-β和 Wnt 信号通路。
Six2 可能是 COAD 治疗的有价值的生物标志物和潜在治疗靶点。
