Analysis of SOX9 Expression in Colorectal Cancer

Abstract

Our purpose was to investigate the role of SOX9, a novel downstream molecule of beta-catenin, in colorectal cancer. Expression of SOX9 and beta-catenin was detected by immunostaining, quantitative real-time reverse transcription-polymerase chain reaction (Q-PCR), and Western blot in colorectal cancer. The correlation between SOX9 or beta-catenin expression and clinicopathologic parameters was also analyzed. Immunostaining, Q-PCR, and Western blot consistently confirmed SOX9 up-regulation in colorectal cancer compared with normal mucosa (P < .05). Immunostaining showed more SOX9+ cells in the lower zone of colonic crypts than in the upper zone (P < .05). Cancers with strong SOX9 immunostaining were significantly associated with a lower 5-year overall survival (40% [17/43] vs low expression, 69% [66/95]; P < .01). The Cox proportional hazards model showed that strong SOX9 expression was an independent adverse prognosticator in colorectal cancer (P < .05). The detection of SOX9 expression might contribute to predicting clinical outcomes for patients with colorectal cancer.

Expression and Clinical Significance of SOX9 in Renal Cell Carcinoma, Bladder Cancer and Penile Cancer

“…It is a downstream effector of SRY, which is dependent on the activity of androgens and the androgen receptor. Several researchers have demonstrated the upregulation of SOX9 and its homologues in different types of cancers [15,18]. Lü et al [18] reported that a strong SOX9 expression is an independent indicator of an adverse prognosis in colorectal cancer.…”

“…Several researchers have demonstrated the upregulation of SOX9 and its homologues in different types of cancers [15,18]. Lü et al [18] reported that a strong SOX9 expression is an independent indicator of an adverse prognosis in colorectal cancer. Qin et al [15] showed that SOX9 is involved in the development and progression of human non-small cell lung cancer, and may serve as a novel and prognostic marker for the disease.…”

Clinical Implications of Intestinal Stem Cell Markers in Colorectal Cancer

“…28 This is in agreement with the expression observed in human colon epithelia, where SOX9 is described as being primarily expressed in the nucleus of cells in the lower proliferative part of the colonic crypts and with a weaker expression in cells toward the luminal surface. [54][55][56]100 Furthermore, inactivation of Sox9 in mice results in aberrant structure of the colon tissue with villus-like protrusions into the lumen, similar to the small intestinal morphology, emphasizing the importance of Sox9 in the small intestinal and colon morphology. 101 Additionally, the goblet cell lineage of the colon is strongly reduced in the Sox9 deficient mice.…”

“…100 The exact role of SOX9 in carcinogenesis and cancer progression is, however, controversial because both oncogenic and tumor-suppressing functions of the protein have been described. 53,55,56,[103][104][105] SOX9 has been shown to be a direct Wnt signaling target of the activated b-catenineTCF4 complex in human colon carcinoma cells, 100 but another study showed that SOX9 potentially inhibit the b-catenineTCF4 complex, suggesting a negative feedback loop. 101 Furthermore, Bmi1 has been identified as a potential SOX9 target in mouse primary cells and transformed cells, hence repressing the tumor suppressors p16 and p19 ARF , leading to cell cycle progression and bypassing of apoptosis.…”

“…The most investigated intestinal stem cell markers in a clinical setting are LGR5, 17,29-41 BMI1, 42-49 MSI1, 50-52 and SOX9. 5,28,[53][54][55][56][57][58][59][60][61] This review evaluates the potential clinical implications of these 4 putative intestinal stem cell markers and their potential role in human CRC.…”