The Clinical Significance Of HPA And HIF-1α Expression In Non-Small Cell Lung Cancer

Objective Lung cancer is one of the most common malignant tumor. The main cause of death is often metastasis. It has been known that neovascularization is a necessary condition for the invasion and metastasis of lung cancer. By detecting of the expressions of heparanase (HPA), hypoxia inducible factor-1α(HIF-1α), CD34 protein and HPA mRNA in non-small cell lung cancer, this study is to investigate the relationships of HPA, HIF-1αand CD34 expression with the carcinogenesis, invasion and metastasis of non-small cell lung cancer, and the relativity between the expression of HPA and HIF-1αin non-small cell lung cancer and their effects on angiogenesis. The results may provide theoretical basis for further revealment of the invasion and metastasis of non-small cell lung cancer.Methods1 The expressions of HPA protein, HIF-1αprotein and CD34 protein in 72 cases of non-small cell lung cancer tissues and 20 cases of adjacent tumor tissues were detected by immunohistochemistry (PV-9000 Polymer Detection System for Immuno-Histological Staining). Mean microvessel density (MVD) was calculated by the expression of CD34 protein.2 The expression of HPA mRNA in 72 cases of non-small cell lung cancer tissues and 20 cases of adjacent tumor tissues was detected by in situ hybridization (ISH).Results1 Expressions of HPA mRNA and protein in non-small cell lung cancer tissues and adjacent tumor tissues: The expressions of HPA mRNA and protein in 72 cases of non-small cell lung cancer tissues and 20 cases of adjacent tumor tissues were detected by ISH and IHC respectively. The results showed that in both mRNA and protein level, the expression of HPA in non-small cell lung cancer tissues (ISH: 75.0%, IHC: 72.2%) was significantly higher than that in adjacent tumor tissues. (ISH: 0.0%, IHC: 0.0%) (P<0.05). Results of ISH and IHC showed that the expression of HPA in non-small cell lung cancer tissues was significantly correlated with lymph node metastasis and TNM stage (P<0.05), but it wasn't correlated with age, sex, tumor size, pathological type or tumor differentiation (P>0.05). There was a close correlation between the expression of HPA mRNA and HPA protein in the non-small cell lung cancer tissues (Pearson coefficient of continency C=0.681).2 Expression of HIF-1αin non-small cell lung cancer tissues and adjacent tumor tissues: The expression of HIF-1αin 72 cases of non-small cell lung cancer tissues and 20 cases of adjacent tumor tissues was detected by IHC. The results showed that the expression of HIF-1αin non-small cell lung cancer tissues (55.6%) was significantly higher than that in adjacent tumor tissues. (0.0%) (P<0.05). Results of IHC showed that the expression of HIF-1αin non-small cell lung cancer tissues was significantly correlated with lymph node metastasis and TNM stage (P<0.05), but it wasn't correlated with age, sex, tumor size, pathological type or tumor differentiation (P>0.05).3 Expression of CD34 (MVD) in non-small cell lung cancer tissues and adjacent tumor tissues: The expression of CD34 in 72 cases of non-small cell lung cancer tissues and 20 cases of adjacent tumor tissues was detected by IHC. The results showed that MVD in non-small cell lung cancer tissues (40.36±11.24) was significantly higher than that in adjacent tumor tissues (14.06±3.52) (P<0.05). Results of IHC showed that MVD in non-small cell lung cancer tissues was significantly correlated with lymph node metastasis and TNM stage (P<0.05), but it wasn't correlated with age, sex, tumor size, pathological type or tumor differentiation (P>0.05).4 Expression of HPA and angiogenesis: In non-small cell lung cancer tissues,MVD with positive expression of HPA (44.24±11.62)was significantly higher than that with negative expression of HPA (30.27±7.32) (P<0.05). It indicated the expression intensity of HPA could be consistent with the value of MVD in cancer tissues.5 Expression of HIF-1αand angiogenesis: In non-small cell lung cancer tissues,MVD with positive expression of HIF-1α(46.62±11.80)was significantly higher than that with negative expression of HIF-1α(33.52±6.53) (P<0.05). It indicated the expression intensity of HIF-1αcould be consistent with the value of MVD in cancer tissues.6 The relationship between HPA mRNA and HIF-1αprotein: In non-small cell lung cancer tissues,there was a significantly positive correlation between the expression of HPA mRNA and HIF-1αprotein(χ2=7.500,P<0.005,C=0.307).7 The relationship between HPA protein and HIF-1αprotein: In non-small cell lung cancer tissues,there was a significantly positive correlation between the expression of HPA protein and HIF-1αprotein(χ2=10.471,P<0.005,C=0.356). Conclusions1 The expressions of HPA mRNA and protein in non-small cell lung cancer tissues were significantly higher than that in adjacent tumor tissues, which indicated that HPA could be correlated with carcinogenesis progression. The expressions of HPA mRNA and protein in non-small cell lung cancer tissues were significantly correlated with lymph node metastasis and TNM stage, but they were no significantly correlated with age, sex, tumor size, pathological type or tumor differentiation. The close correlation between the expression of HPA protein and HPA mRNA in the non-small cell lung cancer tissues indicated that the expression of HPA protein indirectly reflected the expression of HPA mRNA and the high expression of HPA protein could be the result of high transcription of HPA gene.2 The expressions of HIF-1αin non-small cell lung cancer tissues was significantly higher than that in adjacent tumor tissues, which indicated that HPA could be correlated with carcinogenesis progression. The expression of HIF-1αin non-small cell lung cancer tissues was significantly correlated with lymph node metastasis and TNM stage, but it was no significantly correlated with age, sex, tumor size, pathological type or tumor differentiation. 3 The value of MVD in non-small cell lung cancer tissues was significantly higherthan that in adjacent tumor tissues. The value of MVD in non-small cell lung cancer tissues was significantly correlated with lymph node metastasis and TNM stage.4 The expression intensity of HPA was consistent with the value of MVD in non-small cell lung cancer tissues, which indicated that HPA could be one of the important factors in angiogenesis of non-small cell lung cancer. 5 The expression intensity of HIF-1αwas consistent with the value of MVD in non-small cell lung cancer tissues, which indicated that HIF-1αcould be one of the important factors in angiogenesis of non-small cell lung cancer.6 There was a close correlation between the expression of HIF-1αprotein and HPA mRNA in the non-small cell lung cancer tissues, it indicated that HIF-1αcould positively adjust the transcription of HPA gene and induce the transcription of HPA gene.7 There was a positive correlation between the expression of HIF-1αand HPA protein in the non-small cell lung cancer tissues,it indicated that there could be a positive cooperation between HIF-1αand HPA in the carcinogenesis and development of non-small cell lung cancer.