Growing evidence suggests that accumulation of multiple alterations such as activation of proto-oncogenes and inactivation of tumor suppressor genes is responsible for the development and progression of digestive system cancer. Genetic instability of oncogenes such as microsatellite instability (MSI) and loss of heterozygosity (LOH) is probably associated with mutations in genes responsible for tumor-genesis, and they play important roles in tumor clinical pathology. The studies of MSI and LOH of digestive system cancer have been focused on genetic instability of P53, P16 and FHIT, but few studies were seen in gene nm23H1.
A research article to be published on September 28, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Li from Institute of Cell Biology, Zhejiang University used polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) to analyze MSI and LOH of nm23H1 gene, and immunohistochemistry was employed to check the expression of nm23H1 protein. As various researches regarded nm23H1 as metastasis-associated genes in various tumors, the article further investigated the relationship of nm23H1 genetic instability and its clinical pathological behaviors in Chinese with digestive system cancer.
In their study, in gastric, colonic and gallbladder carcinomas, the positive detected MSI was higher in TNM stage ?+? than that of stage ?+?. In gastric, colonic cancer, HCC and gallbladder carcinoma, the positive detected LOH was higher in TNM stage ?+? than stage ?+?, and higher lymphatic metastasis was also observed. For the expression of nm23H1 protein, it was lower in TNM stage ?+? than that in stage ?+?, and higher lymphatic metastasis cases also showed lower nm23H1 expression. Besides, the LOH negative group exhibited higher nm23H1 protein expression when compared to LOH positive group in gastric cancer, HCC and gallbladder cancer. The results indicated that MSI and LOH may independently control the biological behaviors of the digestive system cancers. MSI could serve as an early biological marker for digestive system cancers. Enhanced expression of nm23H1 protein could efficiently inhibit the cancer metastasis and improve the prognosis. The present data strongly suggest that LOH mostly appeared in the late period of digestive system cancer, indicating a higher malignancy and poor prognosis.