SOX9 expression predicts relapse of stage II colon cancer patients

Abstract

The aim of this study was to investigate if the protein expression of sex-determining region y-box 9 (SOX9) in primary tumors could predict relapse of stage II colon cancer patients. One hundred forty-four patients with stage II primary colon cancer were retrospectively enrolled in the study. SOX9 expression was evaluated by immunohistochemistry, and mismatch repair status was assessed by both immunohistochemistry and promoter hypermethylation assay. High SOX9 expression at the invasive front was significantly associated with lower risk of relapse when including the SOX9 expression as a continuous variable (from low to high expression) in univariate (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.94; P = .01) and multivariate Cox proportional hazards analyses (HR, 0.75; 95% CI, 0.58-0.96; P = .02), adjusting for mismatch repair deficiency and histopathologic risk factors. Conversely, low SOX9 expression at the invasive front was significantly associated with high risk of relapse, when including SOX9 expression as a dichotomous variable, in univariate (HR, 2.32; 95% CI, 1.14-4.69; P = .02) and multivariate analyses (HR, 2.32; 95% CI, 1.14-4.69; P = .02), adjusting for histopathologic risk factors and mismatch repair deficiency. In conclusion, high levels of SOX9 of primary stage II colon tumors predict low risk of relapse, whereas low levels of SOX9 predict high risk of relapse. SOX9 may have an important value as a biomarker when evaluating risk of relapse for personalized treatment.

SOX9 is an atypical intestinal tumor suppressor controlling the oncogenic Wnt/ß-catenin signaling

“…This also explains why despite SOX9 being a target of the Wnt/ß-catenin pathway [1] and consequently, is highly expressed in CRC compared to adjacent healthy tissues [9], SOX9 expression level was shown not to provide prognostic values and high levels of SOX9 cannot be considered as a biomarker [29]. Inversely, low levels of SOX9 at the invasive front of the primary tumor have even been shown to be an independent predictor of relapse in stage II colon cancer patients [30]. In addition, SOX9 mutations are frequent in CRC [8] and according to ICGC (http://dcc.icgc.org/web/), the Sox9 gene is in the top 20 mutated genes with high functional impact.…”

The prognostic value of polycomb group protein B‐cell‐specific moloney murine leukemia virus insertion site 1 in stage II colon cancer patients

“…The enrollment, exclusion, and characteristics of patients in this retrospective study cohort have been described in a previously published paper (15). Briefly, the patient cohort included primary tumors from 144 patients diagnosed and treated for primary stage II colon cancer at Glostrup University Hospital, Gentofte University Hospital, and Herlev University Hospital, Denmark.…”

“…Moreover, patients who relapsed within 3 months or died less than a month after primary surgery was excluded from the study. The MMR status of the primary tumor as well as histopathological risk factors, tumor location, age, and gender was registered as previously described (15).…”

Potential roles of microRNAs and ROS in colorectal cancer: diagnostic biomarkers and therapeutic targets

“…SOX9 acts a regulator of Wnt/beta-catenin pathway and a transcriptional target to maintain intestinal epithelium homeostasis [108]. In addition, SOX9 expression is an important biomarker for the prediction of colorectal cancer relapse [109]. MiR-145 also directly targets catenin δ-1 and contributes largely to oncogenic Wnt/beta-catenin signaling in human colon cancer cells (Figure 2) [104].…”