Quiescin Sulfhydryl Oxidase 2 Overexpression Predicts Poor Prognosis and Tumor Progression in Patients With Colorectal Cancer: A Study Based on Data Mining and Clinical Verification

Quiescin 巯基氧化酶 2 过表达预测结直肠癌患者预后不良和肿瘤进展:一项基于数据挖掘和临床验证的研究

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作者:Tao Jiang, Li Zheng, Xia Li, Jia Liu, Hu Song, Yixin Xu, Chenhua Dong, Lianyu Liu, Hongyu Wang, Shuai Wang, Renhao Wang, Jun Song

Background

As a member of the atypical thiol oxidase family, quiescin sulfhydryl oxidase 2 (QSOX2) has been reported to play an important role in several biological processes, but the expression and function of QSOX2 in colorectal cancer (CRC) remains elusive.

Conclusion

QSOX2 overexpression is strongly associated with malignant progression and poor oncological outcomes in CRC. QSOX2 might act as a novel biomarker for prognosis prediction and a new target for biotherapy in CRC.

Methods

The difference of QSOX2 expression, and its relationship with clinicopathological features and prognosis in CRC, was analyzed by bioinformatic analysis and validated by clinical CRC specimen cohort. The functional characterization of QSOX2 was detected via in vitro and vivo experiments in CRC cell lines, while the potential signaling pathways were predicted by Gene Set Enrichment Analysis (GSEA).

Results

Our data based on bioinformatical analysis and clinical validation demonstrated that the expression of QSOX2 in CRC tissues was significantly upregulated. Additionally, the chi-square test, logistic regression analysis, and Fisher's exact test showed that QSOX2 overexpression was significantly correlated with advanced clinicopathological parameters, such as pathological stage and lymph node metastasis. The Kaplan-Meier curves and univariate Cox regression model showed that QSOX2 overexpression predicts poor overall survival (OS) and disease-free survival (DFS) in CRC patients. More importantly, multivariate Cox regression model showed that QSOX2 overexpression could serve as an independent factor for CRC patients. In vitro and vivo data showed that the proliferation and metastasis ability of CRC cells were suppressed on condition of QSOX2 inhibition. In addition, GSEA showed that the QSOX2 high expression phenotype has enriched multiple potential cancer-related signaling pathways.

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