SOX9 is associated with advanced T-stages of clinical stage II colon cancer in young Mexican patients

Colorectal cancer (CRC) is one of the most common malignancies worldwide and includes colon cancer (CC) and rectal cancer (RC). Regarding CC, the development of novel molecular biomarkers for the accurate diagnosis and prognosis, as well as the identification of novel targets for therapeutic intervention, are urgently needed. SRY-related high-mobility group box 9 (SOX9), a transcription factor, is involved in development, and has been associated with the progression of human cancer. However, its underlying clinical and functional effects in CRC have not been fully understood. Therefore, the present study aimed to evaluate the clinical and functional relevance of SOX9 expression in CC. The expression of SOX9 in tumor tissues was evaluated in 97 biopsies from Mexican patients with CC with early-stage I and II disease by immunohistochemistry (IHC). In addition, SOX9 silencing in the HCT116 cell line was performed using specific small interfering RNAs, while downregulation efficiency was verified by reverse transcription-quantitative PCR and immunofluorescence. Spheroid-formation assay was carried out using ultra-low attachment plates. The IHC results showed that SOX9 was upregulated in patients with stage II (91%) and advanced T3 stage (67%) CC. Interestingly, higher SOX9 expression was associated with clinical stage, tumor size and tumor location. Furthermore, increased SOX9 expression was found in relapsed cases with local tumors; however, it was not associated with increased survival probability. Additionally, functional analysis indicated that SOX9 silencing significantly attenuated the sphere-formation capability of HCT116 cells. The present study was the first to evaluate the expression levels of SOX9 in Mexican patients diagnosed with early-stage CC. The aforementioned findings indicated that high SOX9 expression could play an important role in tumorigenesis and be associated with advanced T-stages of clinical-stage II patients, but not with relapse-free survival.