Expression Of Hypoxia Inducible Factor-1a And BNIP3 In Human Non-small Cell Lung Cancer And Their Correlation

Objective:To investigate the expression of Hypoxia inducible factor-1α(HIF-1α) and the Bcl-2/adenovirus E1B 19kDa-interacting protein 3(BNIP3) in human non-small cell lung carcinoma(NSCLC) and their correlation.Methods:We analyzed BNIP3 expression in 45 tumor samples and pair adjacent normal lung tissues and in 14 control normal lung tissues, and the relationship of expression to HIF-1αby reverse transcription-polymerase chain reaction analyses(RT-PCR) and MaxVisionTM immunohistochemical method. Multivariable analysis was used to analyze the relationship between the HIF-1αand BNIP3 expression and histological types, differentiation, TNM clinical staging, lymphatic metastasis, age and cigarette smoking.Results:(1) Compared with the control group, the mRNA levels of HIF-1αand BNIP3 in lung carcinoma tissues were much higher. There was a significant difference between tumors and the control groups(P<0.01). BNIP3 mRNA levels were positively correlated with HIF-1αlevels(r=0.681,P<0.01). The expression of HIF-1αmRNA was high in squamous cell carcinoma(P<0.05). There was a tendency toward higher mRNA levels of HIF-1αin tumors in the advanced stage and with lymph node metastasis, compared to the early stage of cancer and those without lymph node metastasis(P<0.01).No significicant association was found between the expreesion of BNIP3 mRNA and patients' clinicopathologic parameters. (2)In lung carcinoma,the positive expression rates of HIF-1αand BNIP3 proteins were 53.3%, 66.7%, while 4.4%,13.3% in pair adjacent tissues and 7.1%, 7.1% in control normal lung tissues respectively,showing the proteins of HIF-1αand BNIP3 in cancer tissues were significant different to theirs in normal tissues(P<0.01).The positive correlation between HIF-1αand BNIP3 expression was highly significant(rs=0.378, P<0.01). We also found that the expression of HIF-1αwere correlated with histological types and TNM clinical staging(P<0.05).The association between the positive expression rates of HIF-1αproteins and lymphatic metastasis was close to the statistical significance(P=0.08).The association between BNIP3 expression and lymphatic metastasis was also close to the statistical significance(P=0.06).Conclusions:The high expression of HIF-1αand BNIP3 were closely related in non-small cell lung carcinomas, both of them played important role in the carcinogenesis and development of lung carcinoma. HIF-1αand BNIP3 might to be two potential therapeutic targets in NSCLC.