Analysis of SOX9 Expression in Colorectal Cancer

Department of Pathology, School of Medicine, Zhejiang University Department of Anatomical & Cellular Pathology, the Affiliated Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
American Journal of Clinical Pathology (Impact Factor: 2.51). 12/2008; 130(6):897-904. DOI: 10.1309/AJCPW1W8GJBQGCNI
Source: PubMed


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.

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    • "Since it is well recognized that genes and pathways critical for development may also play important roles in cancer development and progression, it is not surprising that SOX9 is involved in cancers. Zhou et al. [9] reported that the elevated expression of SOX9 may be related with the progression of gastric carcinoma; Chakravarty et al. [10] demonstrated that cytoplasmic SOX9 may serve as a valuable prognostic marker for invasive ductal carcinomas and metastatic breast cancer, and its significant correlation with breast tumor cell proliferation implied that SOX9 may directly contribute to the poor clinical outcomes associated with invasive breast cancer; Vidal et al. [11] found that SOX9 expression was a general feature of basal cell carcinoma and adnexal skin neoplasms; Lü et al. [12] suggested that SOX9 expression may be upregulated in colorectal cancer and strong SOX9 expression may be an independent adverse prognosticator in this cancer; Huang et al. [13] indicated that Sox9 may be required for prostate development and prostate cancer initiation; Zhou et al. [14] reported that SOX9 upregulation may be an independent prognostic indicator for the survival of patients with non-small cell lung cancer; Tanaka et al. [15] also found that SOX9 might contribute to carcinogenesis in pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm. In contrast, Passeron et al. [17] analyzed SOX9 expression in melanoma and discovered that SOX9 expression gradually decreased according to disease progress from normal skin to nevi, primary melanoma, and metastatic melanoma. "
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    ABSTRACT: SOX9 plays an important role in bone formation and tumorigenesis. However, its involvement in osteosarcoma is still unclear. The aim of this study was to investigate the expression pattern and the clinical significance of SOX9 in human osteosarcoma. SOX9 mRNA and protein expression levels were detected by RT-PCR and Western blot assays, respectively, using 30 pairs of osteosarcoma and noncancerous bone tissues. Then, immunohistochemistry was performed to analyze the association of SOX9 expression in 166 osteosarcoma tissues with clinicopathological factors or survival of patients. SOX9 expression at mRNA and protein levels were both significantly higher in osteosarcoma tissues than those in corresponding noncancerous bone tissues (both P < 0.001). Immunohistochemical staining indicated that SOX9 localized to the nucleus and high SOX9 expression was observed in 120 of 166 (72.3%) osteosarcoma specimens. In addition, high SOX9 expression was more frequently occurred in osteosarcoma tissues with advanced clinical stage (P = 0.02), positive distant metastasis (P = 0.008) and poor response to chemotherapy (P = 0.02). Osteosarcoma patients with high SOX9 expression had shorter overall survival and disease-free survival (both P < 0.001). Furthermore, the multivariate analysis confirmed that upregulation of SOX9 was an independent and significant prognostic factor to predict poor overall survival and disease-free survival (both P = 0.006). Our data show for the first time that SOX9 is upregulated in aggressive osteosarcoma tissues indicating that SOX9 may participate in the osteosarcoma progression. More importantly, SOX9 status is a useful prognostic factor for predicting the prognosis of osteosarcoma, suggesting that SOX9 may contribute to the optimization of clinical treatments for osteosarcoma patients.Virtual slides: The virtual slides for this article can be found here:
    Full-text · Article · Nov 2013 · Diagnostic Pathology
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    • "Additionally, the morphology of the colon is altered with the appearance of hyperplasia and local crypt dysplasia, suggesting a regulating function for SOX9 in cell proliferation.12 Moreover, SOX9 is expressed in colon cancer9,10,14,15 and gastric cancer.16 A relationship between these cancers and SOX9 suggests that nonampullary duodenal adenocarcinoma may also be related to SOX9 expression. "
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    ABSTRACT: SOX9 is a marker for stem cells in the intestine, and overexpression of SOX9 is found in gastric and colon cancer; however, the expression of SOX9 in nonampullary duodenal adenoma and adenocarcinoma has not yet been evaluated. This study aimed to investigate SOX9 expression in nonampullary duodenal adenoma and adenocarcinoma by immunohistochemistry. We evaluated SOX9 expression in 43 clinical samples (nonampullary duodenal adenoma in 22 lesions and nonampullary duodenal adenocarcinoma in 21 lesions) resected under endoscopic mucosal resection or endoscopic submucosal dissection. SOX9 was expressed in part of the base of the normal duodenal mucosa surrounding adenomas and adenocarcinomas. In contrast, SOX9-positive cells were found in more than half of the crypts from the bottom part of the crypt in all of the 43 samples. Moreover, in 15 adenoma samples (68.2%) and 19 carcinoma samples (90.5%), SOX9 was expressed in more than three-quarters of the crypts from the bottom part of the crypt. SOX9 is overexpressed in nonampullary duodenal adenoma and adenocarcinoma in humans.
    Full-text · Article · Sep 2013 · Gut and liver
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    • "In cancer, SOX9 regulates proliferation, differentiation and metastasis (Bastide et al, 2007; Matheu et al, 2012). Clinical studies in breast, gastric biliary tract and CRC indicate poorer prognosis with tumour SOX9 overexpression (Lü et al, 2008; Zhou et al, 2011; Matheu et al, 2012; Mazur et al, 2012). Hence, considering the mechanistic evidence for the roles of HEY1, HES1 and SOX9 in cancer pathogenesis and the preclinical data implicating Notch signalling chemotherapy responsiveness, we set out to characterise the expression of these NTFs in CRC and to explore a potential role in chemotherapy resistance. "
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    ABSTRACT: Background: The purpose of this study was to evaluate the expression of Notch-induced transcription factors (NTFs) HEY1, HES1 and SOX9 in colorectal cancer (CRC) patients to determine their clinicopathologic and prognostic significance. Methods: Levels of HEY1, HES1 and SOX9 protein were measured by immunohistochemistry in a nonmalignant and malignant tissue microarray of 441 CRC patients, and the findings correlated with pathologic, molecular and clinical variables. Results: The NTFs HEY1, HES1 and SOX9 were overexpressed in tumours relative to colonic mucosa (OR=3.44, P<0.0001; OR=7.40, P<0.0001; OR=4.08 P<0.0001, respectively). HEY1 overexpression was a negative prognostic factor for all CRC patients (HR=1.29, P=0.023) and strongly correlated with perineural and vascular invasion and lymph node (LN) metastasis. In 5-fluorouracil (5-FU)-treated patients, the tumour overexpression of SOX9 correlated with markedly poorer survival (HR=8.72, P=0.034), but had no predictive effect in untreated patients (HR=0.70, P=0.29). When HEY1, HES1 and SOX9 expression were combined to predict survival with chemotherapy, in treated patients there was an additive increase in the risk of death with each NTF overexpressed (HR=2.09, P=0.01), but no prognostic import in the untreated patient group (HR=0.74, P=0.19). Conclusion: The present study is the first to discover that HEY1 overexpression correlates with poorer outcome in CRC, and NTF expression is predictive of CRC patient survival with 5-FU chemotherapy. If confirmed in future studies, testing of NTF expression has the potential to enter routine pathological practice for the selection of patients to undergo chemotherapy alone or in combination with Notch inhibitors.
    Full-text · Article · Jul 2013 · British Journal of Cancer
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