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 immunofiuorescence. 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.
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机译：结直肠癌（CRC）是全球最常见的恶性肿瘤之一，包括结肠癌（CC）和直肠癌（RC）。关于CC，迫切需要开发用于准确诊断和预后的新型分子生物标志物，以及确定治疗干预的新靶点。SRY相关高迁移率基团盒9（SOX9）是一种转录因子，参与发育，并与人类癌症的进展有关。然而，其对结直肠癌的潜在临床和功能影响尚未完全了解。因此，本研究旨在评估 SOX9 表达在 CC 中的临床和功能相关性。通过免疫组织化学 （IHC） 在墨西哥早期 I 期和 II 期 CC 患者的 97 例活检中评估了肿瘤组织中 SOX9 的表达。此外，使用特定的小干扰RNA在HCT116细胞系中进行SOX9沉默，同时通过逆转录定量PCR和免疫荧光验证了下调效率。使用超低附着板进行球状体形成测定。IHC 结果显示，II 期 （91%） 和晚期 T3 期 （67%） CC 患者的 SOX9 上调，有趣的是，较高的 SOX9 表达与临床分期、肿瘤大小和肿瘤位置相关。此外，在局部肿瘤复发病例中发现 SOX9 表达增加;然而，它与生存概率的增加无关。此外，功能分析表明，SOX9沉默显著减弱了HCT116细胞的球体形成能力。本研究首次评估了被诊断为早期 CC 的墨西哥患者中 SOX9 的表达水平。上述发现表明，高SOX9表达可能在肿瘤发生中发挥重要作用，并与临床II期患者的晚期T分期相关，但与无复发生存期无关。
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