Abstract
Transcription factor sex-determining region Y-box 2 (SOX2) involves in the maintenance of cancer stem cells. However, the role of SOX2 in colorectal cancer (CRC) remains unclear. This study was conducted to investigate the effect of SOX2 on CRC. Studies were searched using electronic databases. The combined odds ratios (ORs) or hazard ratios (HRs: multivariate Cox survival analysis) with their 95% confidence intervals (CIs) were calculated. The Cancer Genome Atlas (TCGA) and GEO datasets were further applied to validate the survival effect. The functional analysis of SOX2 was investigated. In this work, 13 studies including 2337 patients were identified, and validation data were enrolled from TCGA and GEO datasets. SOX2 expression was not significantly related to age, gender, microsatellite instability (MSI) status, clinical stage, histological grade, tumor size, pT-stage, lymph node metastasis, distal metastasis, and cancer-specific survival (CSS) but was correlated with worse overall survival (OS: n = 536 patients) (P < 0.05). Furthermore, TCGA data demonstrated similar results, with no significant correlation between SOX2 and pathological characteristics. Further validation data (OS: n = 1408 and disease-free survival (DFS): n = 1367) showed that SOX2 expression was correlated with worse OS (HR = 1.35, 95% CI: 1.11–1.65, P=0.004) and DFS (HR = 1.30, 95% CI: 1.04–1.62, P=0.02). The functional analyses showed that SOX2 involved in cell-cell junction, focal adhesion, extracellular matrix- (ECM-) receptor interaction, and MAP kinase activity. Our findings suggest that SOX2 expression may be correlated with the worse prognosis of CRC.
Highlights
Colorectal cancer (CRC) is one of the most common malignant tumors and a major cause of cancer-related death in the world and in China [1, 2]
For the enrollment of publications, the main inclusion criteria were included as follows: (1) the patients with CRC were reported; (2) studies reported the detection of Sex-determining region Y-box 2 (SOX2) using immunohistochemistry (IHC); (3) expression status of SOX2 was defined from the original articles; (4) studies provided available data to assess the correlation between SOX2 expression and clinicopathological parameters; (5) studies provided sufficient hazard ratio (HR) with 95% confidence interval (CI) to evaluate the prognostic impact of SOX2 expression on CRC patients based on multivariate Cox survival analysis
Expression of SOX2 was evaluated by IHC. 10 studies with 1431 cases evaluated the relationship between SOX2 expression and the clinicopathological parameters [14, 23, 24, 35,36,37,38,39,40,41]
Summary
Colorectal cancer (CRC) is one of the most common malignant tumors and a major cause of cancer-related death in the world and in China [1, 2]. According to the GLOBOCAN estimates, approximately 1,800,977 new cases were diagnosed with CRC, leading to approximately 861,663 deaths due to this disease in 2018 worldwide [1]. Cancer stem cells (CSCs) are a special subpopulation of tumor cells and have the ability and characteristics of selfrenewal and multilineage differentiation and proliferation potential, which are related to tumor progression, metastasis, recurrence, prognosis, and drug resistance [6,7,8]. Many CSC-related markers have been identified and reported to be associated with poor prognosis and resistance to therapy in cancer [9, 10]. SOX2 involves in the migration, invasion, and proliferation of cancer cells and resistance to therapy [15, 16].
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