Abstract
Emerging evidence shows that Homeobox (HOX) genes are important in carcinogenesis, and their dysregulation has been linked with metastatic potential and poor prognosis. This review (PROSPERO-CRD42020190953) aims to systematically investigate the role of HOX genes as biomarkers in CRC and the impact of their modulation on tumour growth and progression. The MEDLINE, EMBASE, Web of Science and Cochrane databases were searched for eligible studies exploring two research questions: (a) the clinicopathological and prognostic significance of HOX dysregulation in patients with CRC and (b) the functional role of HOX genes in CRC progression. Twenty-five studies enrolling 3003 CRC patients, showed that aberrant expression of HOX proteins was significantly related to tumour depth, nodal invasion, distant metastases, advanced stage and poor prognosis. A post-hoc meta-analysis on HOXB9 showed that its overexpression was significantly associated with the presence of distant metastases (pooled OR 4.14, 95% CI 1.64–10.43, I2 = 0%, p = 0.003). Twenty-two preclinical studies showed that HOX proteins are crucially related to tumour growth and metastatic potential by affecting cell proliferation and altering the expression of epithelial-mesenchymal transition modulators. In conclusion, HOX proteins may play vital roles in CRC progression and are associated with overall survival. HOXB9 may be a critical transcription factor in CRC.
Highlights
Colorectal Cancer (CRC) is the most common gastrointestinal malignancy and the third leading cause of cancer-related death worldwide [1,2]
Similar findings with our study were reported by a recent systematic review by Jin et al on HOX genes in gastric cancer (GC) which demonstrated diversity in the dysregulation profile of HOX genes with most of them acting as potential oncogenes and are associated with worse disease characteristics and worse overall survival (OS) [58]
This systematic review shows that altered expression of HOX genes affects CRC progression in vitro and in vivo
Summary
Colorectal Cancer (CRC) is the most common gastrointestinal malignancy and the third leading cause of cancer-related death worldwide [1,2]. Despite significant advances in diagnostic and therapeutic strategies, the prognosis for CRC patients remains poor, indicating that cancerous cells are not entirely eradicated by current therapies, leading to metastatic disease which is the primary cause of cancer-related mortality [3]. Colorectal carcinogenesis is a complex multistep process involving the dysregulation of oncogenes or tumour suppressor genes related to initiation, progression and resistance to therapy [4,5]. HOX proteins control various cellular processes by regulating the expression of several downstream target genes; they can alter cell behaviour such as proliferation, invasion and migration [7].
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