A recent study on melanoma metastases found that those homozygous for the -443C allele expressed significantly higher levels of OPN mRNA www.selleckchem.com/p38-MAPK.html compared to those that were either heterozygous (CT) or homozygous for the −443 T allele . Transcription factor c-Myb binds to the region of the OPN promoter in an allele-specific manner and induces enhanced activity of the -443C compared to the −443 T OPN promoter . Taken
together, these data suggest that the variation at nt −443 in the OPN promoter plays a role in GC progression and metastasis, especially for the CC genotype at nt −443 in the OPN promoter. Whether the polymorphisms of OPN are related to expression of OPN in cancer patients remain unknown. Over-expression of OPN was found VS-4718 molecular weight in lung cancer samples in a previous study , and the alteration of the −443 T → C promoter region could significantly increase the promoter activity by Dual
Luciferase Reporter Assay System . In the present study, we found that the CT genotype at nt −443 in the OPN promoter showed significant differences between stages III + IV and stage I + II lung cancer, but no significant difference between stage IV and sum of other stages of lung cancer (Table 4); and for the CC genotype, there was significant difference between stage IV and other single stages or combination of any other stages. The main reason for this may be due to the limited ERK inhibitor number of patients in CC type subgroups. It is also possible that the CC genotype has more enhanced transcription activity of the region of the OPN promoter compared to CT genotypes . Among total 31 CC genotype patients, 20 patients were diagnosed as bone metastasis, it is extremely high, but there is no significant difference on the ratio of CC type between lung cancer patients and healthy controls. The main reason for this, we hypothesize that OPN is a not key factor for initiating lung cancer, but once the carcinogenesis occurred, OPN will enhance this process effectively, especially for distant metastasis and bone metastasis, which is consistent with
previous study. However, the further study is needed to investigate this hypothesis. There are also some drawbacks in the present study, one of them is because 17-DMAG (Alvespimycin) HCl all the subjects are Chinese individuals, the results should be interpreted with caution and need to be confirmed in larger and ethnically divergent population samples. On the other hand, the number of stage IV patients without bone metastasis in the current study is not high enough, so the large-population research is needed to make stronger conclusion about the association between bone metastasis formation and −433 polymorphisms. Conclusions In summary, -443C/T of OPN is a potential biomarker for predicting prognosis of lung cancer, especially for bone metastasis. Acknowledgments We appreciate China natural funding for support of this research project.