Abstract
BackgroundIncreasing evidences showed that the location of the primary tumor on the right (proximal) or left (distal) side of the colon have a prognostic/predictive value for colon cancer patients. However, the understanding of the molecular mechanisms that contribute to the pathogenesis in different location of colon is still unclear. Probably an important role could be played by genes that control the spatial–temporal development of bodily structures, such as HOX genes.MethodsThe main purpose of this study was to analyze the expression of the paralogous 13 HOX genes and of the HOX regulating lncRNA HOTAIR in distal and proximal CRC cases. We have carried out a Tissue Micro Array with left and right CRC samples associated with all clinical-pathological parameters of patients. The expression of HOX genes was evaluated by immunohistochemistry and the staining of HOTAIR was performed by in situ hybridization using a specifically designed LNA probe.ResultsAll paralogous 13 HOX genes and HOTAIR are silent in normal tissue and expressed in CRC samples. HOXB13, HOXC13 and HOTAIR showed a statistical association with lymph nodes metastasis (p value = 0.003, p value = 0.05, p value = 0.04). HOXB13, HOXC13 and lncRNA HOTAIR are overexpressed in right CRCs samples (p value < 0 and p value = 0.021). HOTAIR is also strongly correlated with HOXB13 (p value = 0.02) and HOXC13 (p value = 0.042) expression.ConclusionsOur data highlighted an important role of posterior HOX genes in colorectal cancer carcinogenesis. Specifically, the aberrant expression of the HOXB13, HOXC13 and HOTAIR in proximal colon cancers could add an important dowel in understanding molecular mechanisms related to tumor pathogenesis in this location.
Highlights
Increasing evidences showed that the location of the primary tumor on the right or left side of the colon have a prognostic/predictive value for colon cancer patients
We focused the attention on the long non-coding RNA hox transcript antisense intergenic RNA (HOTAIR) which controls in trans the expression of the locus HOX D genes and of several genes associated with metastatic progression [18]
Regarding T stage, 3.7% of patients had a primary tumor located in submucosal (T1), 30.5% in muscularis propria (T2), for 51,2% the lesion extended beyond muscularis propria (T3), and for 7.3% invaded the peritoneal surface and/or adjacent organs (T4)
Summary
Increasing evidences showed that the location of the primary tumor on the right (proximal) or left (distal) side of the colon have a prognostic/predictive value for colon cancer patients. The understanding of the molecular mechanisms that contribute to the pathogenesis in different location of colon is still unclear. An important role could be played by genes that control the spatial–temporal development of bodily structures, such as HOX genes. Significant biological differences associated with different embryonic origin of colon (middle intestine for the Tatangelo et al J Transl Med (2018) 16:350 proximal colon and the posterior intestine for the distal colon) were well documented [3]. The understanding of the molecular mechanisms that determine the pathogenesis of the tumor on the right or left side is still unclear. An important role could be played by genes that control the spatio-temporal development of body structures. One of the most studied gene family and whose de-regulation is often associated with carcinogenesis and tumor progression is the Homeobox genes [6]
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