Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity

AIM： To evaluate the role of N-myc downstream- regulated gene 1 （NDRG1） expression in prognosis and survival of colorectal cancer patients with different ethnic backgrounds. METHODS： Because NDRG1 is a downstream target of p53 and hypoxia inducible factor-1α （HIF-1α）, we examined NDRG1 expression together with p53 and HIF-1α by irnmunohistochernistry. A total of 157 colorectal cancer specimens including 80 from Japanese patients and 77 from US patients were examined. The correlation between protein expression with clinicopathological features and survival after surgery was analyzed. RESULTS： NDRG1 protein was significantly increased in colorectal tumor compared with normal epithelium in both Japanese and US patient groups. Expression of NDRG1 protein was significantly correlated with lymphatic invasion, venous invasion, depth of invasion, histopathological type, and Dukes＇ stage in Japanese colorectal cancer patients. NDRG1 expression was correlated to histopathological type, Dukes＇ stage and HIF-1α expression in US-Caucasian patients but not in US-African American patients. Interestingly, Kaplan-Meier survival analysis demonstrated that NDRG1 expression correlated significantly with poorer survival in US-African American patients but not in other patient groups. However, in p53-positive US cases, NDRG1 positivity correlated significantly with better survival. In addition, NDRG1 expression also correlated significantly with improved survival in US patients with stages Ⅲ and IV tumors without chemotherapy. In Japanese patients with stages Ⅱ and Ⅲ tumors, strong NDRG1 staining in p53- positive tumors correlated significantly with improved survival but negatively in patients without chemotherapy. CONCLUSION： NDRG1 expression was correlated with various clinicopathological features and clinical outcomes in colorectal cancer depending on the race/ethnicity of the patients. NDRG1 may serve as a biological basis for the disparity of clinical outcomes of colorectal cancer patients with different ethnic backgrounds.

IL-17A in Ovarian Cancer

Ovarian cancer is the most common malignant disease leading to death among women. IL (interleukin)-17A is the most well-studied member of the IL-17 family, and has been demonstrated to play a critical role in host defenses against various microbial pathogens, as well as against tissue inflammation. T-helper (Th)17 cells that produce interleukin (IL)-17A are of particular importance, because IL-17A exerts a wide variety of biological functions, particularly related to inflammation and the resultant carcinogenesis, as well as immune suppression in patients with cancer, and IL-17A-targeted therapy has been proven to be effective in the treatment of some autoimmune diseases. The pathogenic features of Th17 and IL-17A cells in cancer are still controversial, and Th17 cells appear to promote disease progression, as well as be present in the vicinity of many types of malignant diseases. In cancer patients, MDSC (myeloid-derived suppressor cells), one of the major immunosuppressive immature cells, and VEGF (vascular endothelial growth factor) are reported to correlate each other and strongly connected to IL-17-driven inflammation and malnutrition. In the present review, the latest advances are presented about the basic features of IL-17A and Th17. The function of IL-17A has not been clarified especially in ovarian cancer. This review overview the basic features of IL-17A and the functions in ovarian cancer as well as in other malignant and non-malignant diseases. Increasing our understanding of the interactions between IL-17A and ovarian cancer could lead to new therapeutic strategies in oncology.

Down-regulation of p73 correlates with high histological grade in Japanese with breast carcinomas

Background p73, a homologue of p53, has been located at chromosome lp36-33, a region of frequently observed loss of heterozygosity in breast cancers. The objective of the present study was to investigate the function of p73 in Japanese with breast cancers. Methods Sixty Japanese patients with breast cancer were assessed by polymerase chain reaction single strand confirmation polymorphism analysis and direct sequencing to detect the p73 allele, p73 mRNA levels were also determined in 40 out of 60 patients by reverse-transcriptional polymerase chain reaction. Results We analyzed the entire open reading frame of the p73 gene by polymerase chain reaction single strand confirmation polymorphism and sequencing, and failed to identify any mutations of p73 in the encoding regions detected. Loss of heterozygosity of p73 was infrequent and only found in 9% of breast carcinomas. We revealed a few polymorphisms with a frequency of 13%-29%, which had been reported previously. Down-regulation of p73 mRNA expression was observed in tumor tissues in comparison to the normal breast tissues. A significant inverse correlation was found between p73 transcripts and high histological grade, suggesting that down-regulated p73 expression could be related to poor prognosis in those patients. Conclusion Our results suggest that p73 may serve as a tumor suppressor gene and its expression plays a role in tumorigenesis in Japanese patients with breast cancer.