Department of Hepatobiliary and Pancreatic Surgery, Royal Surrey County Hospital, Guildford GU2 7XX, UK.
School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7HX, UK.
Int J Mol Sci. 2022 Feb 18;23(4):2281. doi: 10.3390/ijms23042281.
As is known, HOXB9 is an important factor affecting disease progression and overall survival (OS) in cancer. However, its role in colorectal cancer (CRC) remains unclear. We aimed to explore the role of HOXB9 in CRC progression and its association with OS in colorectal liver metastases (CRLM). We analysed differential expression in CRC using the Tissue Cancer Genome Atlas database (TCGA). We modulated expression in vitro to assess its impact on cell proliferation and epithelial-mesenchymal transition (EMT). Lastly, we explored the association of HOXB9 protein expression with OS, using an institutional patient cohort ( = 110) who underwent liver resection for CRLM. Furthermore, was upregulated in TCGA-CRC ( = 644) vs. normal tissue ( = 51) and its expression levels were elevated in mutations ( < 0.0001). In vitro, HOXB9 overexpression increased cell proliferation ( < 0.001) and upregulated the mRNA expression of EMT markers (, , , , and ) while downregulated , ( < 0.05 for all comparisons). Conversely, silencing disrupted cell growth ( < 0.0001). High HOXB9 expression (HR = 3.82, 95% CI: 1.59-9.2, = 0.003) was independently associated with worse OS in CRLM-HOXB9-expressing patients after liver resection. In conclusion, HOXB9 may be associated with worse OS in CRLM and may promote CRC progression, whereas HOXB9 silencing may inhibit CRC growth.
众所周知,HOXB9 是影响癌症疾病进展和总生存期(OS)的重要因素。然而,其在结直肠癌(CRC)中的作用尚不清楚。我们旨在探讨 HOXB9 在 CRC 进展中的作用及其与结直肠肝转移(CRLM)患者 OS 的关系。我们使用组织癌症基因组图谱数据库(TCGA)分析了 CRC 中的差异表达。我们在体外调节表达,以评估其对细胞增殖和上皮-间充质转化(EMT)的影响。最后,我们使用一个机构患者队列(n=110),对接受肝切除术治疗 CRLM 的患者进行了 HOXB9 蛋白表达与 OS 之间的关系研究。此外,TCGA-CRC(n=644)与正常组织(n=51)相比,HOXB9 表达上调,并且在 突变中表达水平升高(<0.0001)。在体外,HOXB9 过表达增加了细胞增殖(<0.001),上调了 EMT 标志物(、、、、和)的 mRNA 表达,同时下调了(所有比较均<0.05)。相反,沉默抑制了细胞生长(<0.0001)。HOXB9 高表达(HR=3.82,95%CI:1.59-9.2,=0.003)与肝切除术后 CRLM-HOXB9 表达患者的 OS 较差独立相关。总之,HOXB9 可能与 CRLM 的较差 OS 相关,并可能促进 CRC 的进展,而 HOXB9 沉默可能抑制 CRC 的生长。