Abstract
It was recently reported that increased SOX9 expression drives tumor growth and promotes cancer invasion during human tumorigenicity and metastasis. However, the prognostic value of SOX9 for the survival of patients with solid tumors remains controversial. The present meta-analysis was thus performed to highlight the link between dysregulated SOX9 expression and prognosis in cancer patients. A systematic literature search was conducted using the electronic databases PubMed, Web of Science and Embase to identify eligible studies. A random-effects meta-analytical model was employed to correlate SOX9 expression with overall survival (OS), disease-free survival (DFS) and clinicopathological features. In total, 17 studies with 3307 patients were eligible for the final analysis. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) suggested that high SOX9 expression has an unfavourable impact on OS (HR = 1.66, 95% CI 1.36–2.02, P < 0.001) and DFS (HR = 3.54, 95% CI 2.29–5.47, P = 0.008) in multivariate analysis. Additionally, the pooled odds ratios (ORs) indicated that SOX9 over-expression is associated with large tumor size, lymph node metastasis, distant metastasis and a higher clinical stage. Overall, these results indicated that SOX9 over-expression in patients with solid tumors might be related to poor prognosis and could serve as a potential predictive marker of poor clinicopathological prognosis factor.
Highlights
SOX9 is a member of SOX [SRY-related high mobility group (HMG) box] family and serves as a transcription factor that plays a central role in the development and differentiation of multiple cell lineages [1]
A plenty of studies investigated the correlation between SOX9 expression and prognosis in cancer patients, and demonstrated that upregulated expression of SOX9 in malignant tumors was correlated with poor prognosis in patients with different types of solid tumors such as chordoma [13], osteosarcoma [14,15,16], colorectal carcinoma [17, 18], esophageal squamous cell carcinoma [10, 19], breast cancer [20,21,22,23], hepatocellular carcinoma (HCC) [24, 25], glioma [26], chondrosarcoma [27], gastric cancer [28,29,30], melanoma [31], pancreatic ductal adenocarcinoma (PDAC) [32], ovarian cancer (OC) [33], prostate cancer [34, 35] and non-small cell lung cancer (NSCLC) [36]
The transcription factor SOX9 is a member of SOX family proteins which contain a highly conserved HMG domain that was first identified in Sry, an essential factor involved in mammalian male sex determination [43]
Summary
SOX9 is a member of SOX [SRY (sex determining region Y)-related high mobility group (HMG) box] family and serves as a transcription factor that plays a central role in the development and differentiation of multiple cell lineages [1]. SOX9 overexpression significantly induces the proliferation and tumorigenicity of human esophageal squamous cell cancer (ESCC) cells by increasing the expression of phosphorylated Akt and its downstream targets such as phosphorylated forkhead box O (FOXO) 1 and phosphorylated FOXO3, two members of FOXO family of transcription factors [9]. Knockdown of SOX9 suppresses chondrosarcoma growth www.impactjournals.com/oncotarget and migration [11], and induces apoptosis, cell cycle arrest as well as decreased expression of cancer stem cell markers [12,13,14]. The exact clinical and prognostic merit of SOX9 overexpression in various solid tumors remains unclear. Most of these studies included only a limited number of patients, and the results of each individual study were not conclusive
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