Mihyang Ha1, Jayoung Kim2, Su Min Park2, Chae Mi Hong2, Myoung-Eun Han1, Parkyong Song2, Chi-Dug Kang2,3, Dongjun Lee2, Yun Hak Kim1,4,5, Jin Hur2, Sae-Ock Oh1. 1. Department of Anatomy, Pusan National University School of Medicine, Yangsan, Republic of Korea. 2. Department of Convergence Medicine, Pusan National University School of Medicine, Yangsan, Republic of Korea. 3. Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Republic of Korea. 4. Department of Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Republic of Korea. 5. Biomedical Research Institute, Pusan National University School of Medicine, Yangsan, Republic of Korea.
Abstract
Introduction: Zinc finger homeobox 4 (ZFHX4) is a crucial molecular regulator of tumor-initiating stem cell-like functions. Objective: This study aimed to determine the role of ZFHX4 in the progression of ovarian serous cystadenocarcinoma (OSC). Methods: Differential gene expression among low-stage (stages I and II), high-stage (stages III and IV), low-grade (grades I and II), and high-grade (grades III and IV) OSC patients was identified using four independent cohorts from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). We compared ZFHX4 expression as a prognostic factor using Kaplan-Meier survival curves, multivariate analysis, the time-dependent area under the curve (AUC) of Uno's C-index, and the AUC of the receiver operating characteristics at 4 years post diagnosis. Results: ZFHX4 gene expression in high-stage tumors is significantly higher than in low-stage tumors (TCGA, p = 0.007; GSE9891, p = 0.001). Kaplan-Meier analysis revealed that elevated expression of ZFHX4 was associated with a poor prognosis in OSC patients for all cohorts, regardless of stage and grade (TCGA, p = 1e-04; GSE9891, p = 0.0044; GSE13876, p = 0.00078; GSE26712, p = 0.039). Analysis of C-indices and the area under the receiver operating characteristic curve further supported this result (C-index: TCGA, 0.599; GSE9891, 0.642; GSE13876, 0.585; GSE26712, 0.597). Moreover, univariate and multivariate Cox hazards analyses confirmed the prognostic significance of ZFHX4 levels. Conclusion: Collectively, these findings suggest that ZFHX4 is a potential prognostic factor for OSC.
Introduction: Zinc finger homeobox 4 (ZFHX4) is a crucial molecular regulator of tumor-initiating stem cell-like functions. Objective: This study aimed to determine the role of ZFHX4 in the progression of ovarian serous cystadenocarcinoma (OSC). Methods: Differential gene expression among low-stage (stages I and II), high-stage (stages III and IV), low-grade (grades I and II), and high-grade (grades III and IV) OSCpatients was identified using four independent cohorts from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). We compared ZFHX4 expression as a prognostic factor using Kaplan-Meier survival curves, multivariate analysis, the time-dependent area under the curve (AUC) of Uno's C-index, and the AUC of the receiver operating characteristics at 4 years post diagnosis. Results:ZFHX4 gene expression in high-stage tumors is significantly higher than in low-stage tumors (TCGA, p = 0.007; GSE9891, p = 0.001). Kaplan-Meier analysis revealed that elevated expression of ZFHX4 was associated with a poor prognosis in OSCpatients for all cohorts, regardless of stage and grade (TCGA, p = 1e-04; GSE9891, p = 0.0044; GSE13876, p = 0.00078; GSE26712, p = 0.039). Analysis of C-indices and the area under the receiver operating characteristic curve further supported this result (C-index: TCGA, 0.599; GSE9891, 0.642; GSE13876, 0.585; GSE26712, 0.597). Moreover, univariate and multivariate Cox hazards analyses confirmed the prognostic significance of ZFHX4 levels. Conclusion: Collectively, these findings suggest that ZFHX4 is a potential prognostic factor for OSC.
Entities:
Keywords:
International Cancer Genome Consortium; ZFHX4; ovarian serous cystadenocarcinoma; prognosis; the Cancer Genome Atlas