HOXB9 Overexpression Promotes Colorectal Cancer Progression and Is Associated with Worse Survival in Liver Resection Patients for Colorectal Liver Metastases

Abstract

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 HOXB9 expression in CRC using the Tissue Cancer Genome Atlas database (TCGA). We modulated HOXB9 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 (n = 110) who underwent liver resection for CRLM. Furthermore, HOXB9 was upregulated in TCGA-CRC (n = 644) vs. normal tissue (n = 51) and its expression levels were elevated in KRAS mutations (p < 0.0001). In vitro, HOXB9 overexpression increased cell proliferation (p < 0.001) and upregulated the mRNA expression of EMT markers (VIM, CDH2, ZEB1, ZEB2, SNAI1 and SNAI2) while downregulated CDH1, (p < 0.05 for all comparisons). Conversely, HOXB9 silencing disrupted cell growth (p < 0.0001). High HOXB9 expression (HR = 3.82, 95% CI: 1.59–9.2, p = 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.

Comprehensive analysis of a homeobox family gene signature in clear cell renal cell carcinoma with regard to prognosis and immune significance

“…The aberrant expression of HOXB9 in tumors was not only prognostic predictor but also indicator of response to target therapy. Protein encoded by HOXB9 functioned as oncoprotein and could accelerate cell proliferation and invasion in endometrial cancer, colorectal cancer, and hepatocellular carcinoma cells ( 58 – 60 ). However, HOXB9 could also delay tumor progression in other kinds of tumors such as gastric cancer and pancreatic cancer ( 61 , 62 ).…”

Effects of metronidazole on colorectal cancer occurrence and colorectal cancer liver metastases by regulating Fusobacterium nucleatum in mice

“…7 Despite great advances in the diagnostic and therapeutic strategies, the prognosis still remains dismal because most of the patients develop metachronous or synchronous CRC liver metastases (CRLM). 8 The mechanism of CRC occurrence and metastasis is identified as a multistep and multifactorial process, which may involve various genetic alterations and biological pathways. 9 Studies have found that probiotics can be used as promising ingredients and play vital molecular roles for treating infectious diseases and intestinal-related inflammation.…”

“…The liver is the most common site of CRC metastasis, of which 15%–20% of the patients will be candidates for hepatectomy 7 . Despite great advances in the diagnostic and therapeutic strategies, the prognosis still remains dismal because most of the patients develop metachronous or synchronous CRC liver metastases (CRLM) 8 …”

“… 7 Despite great advances in the diagnostic and therapeutic strategies, the prognosis still remains dismal because most of the patients develop metachronous or synchronous CRC liver metastases (CRLM). 8 …”

Identification and validation of a novel HOX-related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomas

“…Most of the 39 HOX genes are aberrantly expressed in solid tumors, and their expression is frequently altered in cancer, including lung (Li L. et al, 2019), colon (Bhatlekar et al, 2019;Martinou et al, 2022), breast (de Bessa Garcia et al, 2020), pancreas (Kuo et al, 2019), prostate (Hatanaka et al, 2019), and ovarian cancers (Idaikkadar et al, 2019). Most HOX genes are expressed in the developing vertebrate central nervous system (CNS), where they play essential functions.…”