Expression of Oncogenic Molecules in Pediatric Ulcerative Colitis

Abstract

<b><i>Introduction:</i></b> Long-term disease duration of ulcerative colitis (UC) is known to increase the risk of developing colorectal cancer in adults; however, this association has not been genetically analyzed in children with UC. Herein, we examined the expression of cancer-related genes in the colonic mucosa of pediatric UC patients and their risk of developing colorectal cancer. <b><i>Methods:</i></b> Microarray analysis of cancer-related gene expression was conducted on rectal mucosa biopsy specimens randomly selected from pediatric cases, including 4 active-phase UC cases, 3 remission-phase UC cases, and 3 irritable bowel syndrome control cases. The subject pool was then expanded to 10 active-phase cases, 10 remission-phase cases, and 10 controls, which were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemical staining. <b><i>Results:</i></b> The microarray results indicated significantly higher expression levels of cancer-related genes <i>PIM2</i> and <i>SPI1</i> in the active group than in the remission and control groups (<i>p</i> &#x3c; 0.05). Real-time PCR confirmed that <i>PIM2</i> and <i>SPI1</i> expression levels were significantly higher, whereas <i>TP53</i> and <i>APC</i> expression levels were significantly lower, in the active-phase group than in the remission and control groups (<i>p</i> &#x3c; 0.05). Immunohistochemical staining for PIM2, SPI1, TP53, and APC proteins supported the real-time PCR results. <b><i>Conclusions:</i></b> Expression levels of previously unreported cancer-related genes in adult UC patients were significantly higher in pediatric UC patients than in controls. Inflammation of the gastrointestinal mucosa increased the expression levels of cancer-related genes even in childhood-onset UC cases, suggesting that chronic inflammation from childhood may increase the risk of colorectal cancer development.