探討小細胞肺癌組織中缺氧誘導因子-1a 之表現量與預後狀況之相關性

Abstract

Hypoxia is a key factor in tumor angiogenesis, metastasis and resistance to chemotherapy, immunotherapy, or radiotherapy that may indicate poor prognosis. Hypoxia may induce accumulation of hypoxia inducible factor-1a (HIF-1a), which is a result of stabilization of HIF-1a, not increase transcription or translation of its m-RNA. However, the half life of HIF-1a is short. (less than 5 minutes) Under nomoxic condition, HIF-1a is constitutively synthesized and degraded by 26S proteosome pathway at the same time, therefore, keeping the steady state level below the detectable limit. When hypoxia develops, HIF-1a is accumulated largely. Increased HIF-1a expression has been reported in many previous papers to be associated with poor prognosis in breast cancer, oropharyngeal cancer, cervical cancer and non-small cell lung cancer. There is not data showed the association between the HIF-1a expression and the prognosis of small cell lung cancer. This study is designed to examine the role of HIF-1a expression to influence the prognosis of small cell lung cancer. In this study, forty-three small cell lung cancer cases were stained by immunohistochemistry of HIF-1a and scored by the different level of HIF-1a expression. Further, analysis the HIF-1a expression and patient’s survival by Kaplan and Meier survival curve and log-rank test. The results showed that 90.7% small cell lung cancer expressed HIF-1a by immunostain and the level of HIF-1a overexpression was inversely related to survival time (high level : 16.5+1.7 weeks, low level : 48.6+3.4 weeks, P<0.001). Besides, the tumor expressed high HIF-1a level was significantly associated with earlier distant metastasis. Compare with non-small cell lung cancer, the expression of HIF-1a in small cell lung cancer was more predominate. It might explain why small cell lung cancer without treatment was more malignant and earlier metastasis. In conclusion, as same as many previous studies reported that the higher HIF-1a expression indicated a worse prognosis. In our study, the patient of small cell lung cancer with HIF-1a overexpression had a high potential to early metastasis and a short survival time.