Overexpression of Sine Oculis Homeobox Homolog 2 Predicts Poor Survival and Clinical Parameters of Patients with Colon Adenocarcinoma.

OBJECTIVE

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).

METHODS

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.

RESULTS

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.

CONCLUSIONS

Six2 may be a valuable biomarker and potential therapeutic target for the treatment of COAD.