Positive Expression Rates Of HIF-1α Research Articles

Prediction of postoperative survival of triple-negative breast cancer based on nomogram model combined with expression of HIF-1α and c-myc.

The aims of this study were to explore the expression of hypoxia inducible factor-1α (HIF-1α) and c-myc protein in triple-negative breast cancer (TNBC) and its clinical prognostic significance, and to establish a prediction model for postoperative survival of TNBC based on nomogram.A total of 87 patients with TNBC at the Department of Breast Surgery, Beijing Chaoyang Hospital, Capital Medical University from January 2012 to December 2015 were enrolled in this study. Immunohistochemistry was performed to detect the expression of HIF-1α and c-myc protein in breast cancer tissues. Cox regression analyses were performed to explore the correlation between HIF-1α/c-myc expression and clinical pathological parameters as well as prognosis. Receiver-operating characteristic curve was generated for cox multivariate analysis. A nomogram was generated based on the cox multivariate analysis, and a calibration curve was prepared for the nomogram to evaluate the consistency between the predicted probability of the nomogram and the actual observed probability. The stability of nomogram model was validated with an external cohort including 39 TNBC patients.The positive expression rates of HIF-1α and c-myc protein in breast cancer tissues were 41.4% (36/87) and 55.2% (48/87), respectively. HIF-1α expression was significantly correlated with age, tumor diameter, histological grade, lymph node status, and tumor TNM stage; c-myc expression was significantly associated with tumor diameter, histological grade, lymph node status, and tumor TNM stage. Cox univariate and multivariate analyses showed that HIF-1α and c-myc protein expression, histological grade, lymph node status, and tumor TNM stage were the independent risk factors for postoperative survival in TNBC patients. The AUC of prediction model was 0.843 (0.809–0.887). The nomogram could predict the probability of 3-year disease-free survival according to each patient's condition. The calibration curve displayed good agreement of the predicted probability with the actual observed probability, indicating that the nomogram model had great value of prediction. The external validation indicated the prediction model had good stability.HIF-1α-positive expression, c-myc positive expression, histological grade III, lymph node positive, and TNM stage III tumors suggested that TNBC patients had a poor prognosis. This prediction model can be used to predict postoperative survival of TNBC.

Clinical research on the expression of three vascular regulatory factors in different morphological regions of Marjolin ulcer and their relationship with angiogenesis

Objective: To investigate the expressions of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1α), and epidermal growth factor receptor (EGFR) in different morphological regions of Marjolin ulcer and their clinical relationship with angiogenesis. Methods: From January 2012 to December 2017, the patients admitted to our hospital who met the inclusion criteria were selected, including 92 patients with Marjolin ulcer [56 males and 36 females, aged (55±15) years], 100 patients with chronic non-cancerous skin ulcer [59 males and 41 females, aged (51±16) years], and 100 patients performed with other skin-related surgery [58 males and 42 females, aged (52±15) years], and they were enrolled into Marjolin ulcer group (MU), chronic non-cancerous ulcer group (CNU), and other skin surgery group (OSS) respectively. The etiology, pathogenic site, ulcer diameter, and course of patients in group MU were retrospectively analyzed. Ulcer tissue specimens from patients of group MU and group CNU and specimens of normal skin tissue attached to the tissue resected during operation from patients of group OSS were collected. The expressions of VEGF, HIF-1α, EGFR, and CD34 in the above-mentioned tissue and the surrounding normal skin, ulcer, epitheliomatous hyperplasia, and canceration areas in Marjolin ulcer tissue were detected by immunohistochemical method, and the positive expression rate and protein expression level were calculated. Data were processed with Pearson chi-square test, Mann-Whitney U test, Bonferroni method, and Bonferroni correction, and Spearman correlation analysis was used to analyze the relationship among the total protein expression levels. Results: In group MU, burns accounted for 91.3% (84/92) of the causes of patients, 44.6% (41/92) of the patients had tumors in the lower extremities, 62.0% (57/92) of the patients had skin ulcer diameter of 2.1-5.0 cm, and 75.0% (69/92) of the patients had a course of disease of more than 20 years. The positive rates of VEGF, HIF-1α, and EGFR in ulcer tissue of patients in group CNU were 41.0% (41/100), 77.0% (77/100), and 83.0% (83/100), respectively, significantly higher than those of normal skin tissue of patients in group OSS [12.0% (12/100), 45.0% (45/100), and 67.0% (67/100), χ(2)=21.589, 21.522, 6.827, P<0.01]. The positive rates of VEGF, HIF-1α, and EGFR in ulcer tissue of patients in group MU were 91.3% (84/92), 100.0% (92/92), and 100.0% (92/92), respectively, which were significantly higher than those in corresponding tissue of patients in group CNU and group OSS (χ(2)=53.372, 24.772, 17.159; 120.543, 72.777, 36.661, P<0.01). In ulcer tissue of patients in group MU, the positive expression rates of VEGF in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than the rate in surrounding normal skin area (χ(2)=87.120, 42.368, 89.624, P<0.01); the positive expression rates of VEGF in canceration and ulcer areas were significantly higher than the rate in epitheliomatous hyperplasia area (χ(2)=22.586, 16.060, P<0.01). In ulcer tissue of patients in group MU, the positive expression rates of EGFR in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than the rate in surrounding normal skin area (χ(2)=21.679, 27.600, 27.600, P<0.01), but the positive expression rates of HIF-1α in four morphological areas were similar (χ(2)=3.008, P>0.05). In ulcer tissue of patients in group MU, the protein expression levels of VEGF and CD34 in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than those in surrounding normal skin area (Z=-6.765, -6.819; -6.765, -6.640; -6.765, -6.819, P<0.01), the protein expression levels of VEGF and CD34 in epitheliomatous hyperplasia area were significantly lower than those in ulcer area (Z=-4.484, -5.266, P<0.01), and the protein expression levels of VEGF and CD34 in canceration area were significantly higher than those in ulcer area (Z=-6.427, -6.723, P<0.01) and epitheliomatous hyperplasia area (Z=-6.427, -6.462, P<0.01). In ulcer tissue of patients in group MU, the protein expression levels of HIF-1α and EGFR in ulcer, epitheliomatous hyperplasia, and canceration areas were significantly higher than those in surrounding normal skin area (Z=-6.819, -6.393; -6.819, -6.393; -6.819, -6.393, P<0.01), the protein expression levels of HIF-1α and EGFR in ulcer area were significantly lower than those in epitheliomatous hyperplasia and canceration areas (Z=-6.118, -5.638; -6.640, -6.393, P<0.01), and the protein expression levels of HIF-1α and EGFR in canceration area were significantly higher than those in epitheliomatous hyperplasia area (Z=-6.558, -6.819, P<0.01). In ulcer tissue of patients in group MU, the total protein expression levels of VEGF, HIF-1α, and EGFR were significantly positively correlated with the total protein expression level of CD34 (r=0.772, 0.415, 0.502, P<0.01) respectively; the total protein expression level of EGFR was significantly positively correlated with that of HIF-1α (r=0.839, P<0.01), both of which were significantly positively correlated with the total protein expression level of VEGF (r=0.531, 0.440, P<0.01) respectively. Conclusions: The expressions of VEGF, HIF-1α, and EGFR are the highest in Marjolin ulcer canceration area, and EGFR may promote angiogenesis through HIF-1α or directly increasing the expression of VEGF.

Expression significance and potential mechanism of hypoxia-inducible factor 1 alpha in patients with myelodysplastic syndromes.

ObjectiveTo investigate the expression level and potential mechanism of hypoxia‐inducible factor 1 alpha (HIF‐1α) in patients with myelodysplastic syndromes (MDS).MethodsImmunohistochemistry (IHC) techniques were used to examine the protein expression of HIF‐1α in paraffin‐embedded myeloid tissues from 82 patients with MDS and 33 controls (patients with lymphoma that is not invading myeloid tissues). In addition, the associations between the protein expression of HIF‐1α and clinical parameters were examined. To further investigate the significance of HIF‐1α expression in MDS patients, the researchers not only extracted the data about HIF‐1α expression from MDS‐related microarrays but also analyzed the correlation between the level of HIF‐1α expression and MDS. The microRNA (miRNA) targeting HIF‐1α was predicted and verified with a dual luciferase experiment.ResultsImmunohistochemistry revealed that the positive expression rate of HIF‐1α in the bone marrow of patients with MDS was 90.24%. This rate was remarkably higher than that of the controls (72.73%) and was statistically significant (P < .05), which indicated that HIF‐1α was upregulated in the myeloid tissues of MDS patients. For the GSE2779, GSE18366, GSE41130, and GSE61853 microarrays, the average expression of HIF‐1α in MDS patients was higher than in the controls. Particularly for the GSE18366 microarray, HIF‐1α expression was considerably higher in MDS patients than in the controls (P < .05). It was predicted that miR‐93‐5p had a site for binding with HIF‐1α, and a dual luciferase experiment confirmed that miR‐93‐5p could bind with HIF‐1α.ConclusionThe upregulated expression of HIF‐1α was examined in the myeloid tissues of MDS patients. The presence of HIF‐1α (+) suggested an unsatisfactory prognosis for patients, which could assist in the diagnosis of MDS. In addition, miR‐93‐5p could bind to HIF‐1α by targeting, showing its potential to be the target of HIF‐1α in MDS.

Expressions and correlation analysis of HIF-1α, survivin and VEGF in patients with hepatocarcinoma.

To investigate the expressions of HIF-1α, surviving, and VEGF in patients with hepatocarcinoma as well as the correlation analysis among them. 65 patients, who were admitted to our hospital and diagnosed as hepatocarcinoma from January 2014 to October 2015, were selected as hepatocarcinoma group, while 50 healthy cases that do not have hepatocarcinoma were selected as normal control group. The expression levels of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group and normal liver tissues of control group were detected by immunohistochemical (SP) staining method; then, the correlation among them was explored. The expression levels of HIF-1α, surviving, and VEGF protein in hepatocarcinoma tissues and corresponding normal tissues were detected by Western blot. The positive expression rate of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group was respectively 46.2%, 55.4%, and 61.5%, significantly higher than that in cancer adjacent normal liver tissues of control group which was 2%, 2%, and 2%, and the differences were statistically significant (p<0.05). The expressions of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of patients with hepatocarcinoma were correlated with clinical stage, tumor differentiation degree and extrahepatic metastasis (p<0.05), but were not related to gender and tumor size (p>0.05). By Spearman rank correlation analysis, it could be seen that HIF-1α expression was positively correlated with VEGF protein expression in hepatocarcinoma tissues (r=0.683, p<0.05). Survivin expression was positively correlated with VEGF protein expression (r=0.717, p<0.05). There was no significant correlation between HIF-1α expression and survivin expression (p>0.05). The relative quantitative value of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues of hepatocarcinoma group was respectively 3.04±0.23, 2.26±0.31, and 2.57±0.36, significantly higher than that in cancer adjacent liver tissues of control group which was 1.07±0.17, 1.31±0.27, and 1.42±0.43, and the differences were statistically significant (p<0.05). From Western blot electrophoresis scanning, it could be seen that the expressions of HIF-1α, surviving, and VEGF in hepatocarcinoma tissues were higher than those in cancer adjacent normal liver tissues. The expressions of HIF-1α, surviving, and VEGF played important roles in the occurrence, invasion, and metastasis of hepatocarcinoma. In hepatocarcinoma tissues, HIF-1α, and survivin protein expression was positively correlated with VEGF expression, but survivin protein was not related to HIF-1α expression, which indicated that HIF-1α and survivin may inhibit the apoptosis of hepatocarcinoma cells and promote tumor angiogenesis by up-regulating the expression of VEGF protein, thus accelerating the occurrence and development of hepatocarcinoma.

Expressions of HIF-1α and CA9 in breast carcinoma and their relationships with basal-like subtype

Objective To study the expressions of hypoxia inducible factor-1α (HIF-1α) and carbo-nic anhydrase 9 (CA9) in different molecular subtypes of breast carcinoma and their relationships with basal-like subtype. Methods The expressions of HIF-1α and CA9 were detected by immunohistochemistry in five subtypes of breast carcinoma (n=803). The relationships of the expressions of HIF-1α and CA9 with the clinicopathologic parameters of basal-like subtype and with the prognosis of patients were analyzed. Results The positive expression rates of HIF-1α and CA9 protein in breast carcinoma were much higher than those in para-tumor breast tissues (43.96% vs. 3.86%, χ2=354.858, P<0.001; 19.80% vs. 4.61%, χ2=86.495, P<0.001). The positive expression rates of HIF-1α in Luminal A, Luminal B, epidermal growth factor receptor-2 (HER-2) over-expression, basal-like and normal breast-like subtypes were 31.97%, 25.00%, 56.06%, 77.89% and 55.76% respectively, and the positive expression rates of CA9 were 7.48%, 5.56%, 60.61%, 40.00% and 27.88% respectively, with significant differences (χ2=88.628, P<0.001; χ2=147.128, P<0.001). The positive expression rates of HIF-1α and CA9 in estrogen receptor (ER)-negative breast carcinomas (HER-2 over-expression, basal-like and normal breast-like) were significantly higher than those in ER-positive subtypes (Luminal A and Luminal B, all P<0.005). There was a significant positive correlation between HIF-1α and CA9 (C=0.315, P=0.001), and both were correlated with the lymph node metastasis (χ2=4.542, P=0.033; χ2=7.025, P=0.008), pTNM stage (χ2=5.390, P=0.020; χ2=10.179, P=0.001) and poor prognosis (χ2=4.353, P=0.037; χ2=6.056, P=0.014) of basal-like subtype. Conclusion Over-expressions of HIF-1α and CA9 may be related to the ER-negative breast cancer more closely, and both may play important roles in the occurrence and development of basal-like subtype. Over-expressions of HIF-1α and CA9 may suggest the poorer prognosis of patients with basal-like breast carcinoma. Key words: Breast neoplasms; Hypoxia-inducible factor 1, alpha subunit; Carbonic anhydrases; Basal-like subtype

Expressions of HIF-1α and VEGF in rhabdomyosarcoma and their clinical significance

Objective: To investigate the expressions of HIF-1α (hypoxia inducible factor-1α) and VEGF (vascular endothelial growth factor) in rhabdomyosarcoma and their clinical significance. Methods: The expressions of HIF-1α and VEGF preteins in 70 cases of rhabdomyosarcoma were detected by immunohistochemistry, and the correlations of the expressions of HIF-1α and VEGF with the clinicopathological characteristics and the prognosis were analyzed. Results: The positive-expression rates of HIF-1α and VEGF in rhabdomyosarcoma tissues were 75.7% (53/70) and 72.9% (51/70), respectively. HIF-1α expression was positively correlated to VEGF expression (r = 0.554, P = 0.000). HIF-1α expression was significantly associated with the factors of gender (P = 0.035), tumor size (P = 0.016) and clinical staging (P = 0.008), but it was not associated with the age (P = 0.555), pathological type (P = 0.625) and lymph node metastasis (P = 0.750). The three-year overall survival rates of HIF-1α-negative patients and HIF-1α-positive patients were 54.5% and 38.0%, respectively (P = 0.045). VEGF expression was significantly associated with clinical stage (P = 0.026), but it was not associated with the age (P = 0.478), gender (P = 0.944), tumor size (P = 0.535), pathological type (P = 0.399) and lymph node metastasis (P = 0.356). The three-year overall survival rates of VEGF-negative patients and VEGF-positive patients were 68.1% and 31.1% (P = 0.011). COX regression model showed that the factors of VEGF expression (P = 0.005), clinical staging (P = 0.004) and tumor size (P = 0.000) were independent predictors of poor prognosis of rhabdomyosarcoma. HIF-1α could not be considered as an independent prognostic factor of rhabdomyosarcoma (P = 0.845). Conclusion: The overexpression of HIF-1α and VEGF in rhabdomyosarcoma is related to clinical staging. HIF-1α expression is associated with VEGF expression, and VEGF is an independent predictor of poor prognosis of rhabdomyosarcoma. DOI:10.3781/j.issn.1000-7431.2012.08.012

Expression of HIF-1α and CAIX in nasopharyngeal carcinoma and their correlation with patients' prognosis.

This study investigates the expression of hypoxia-inducible factor-l alpha (HIF-1α) and carbonic anhydrase IX (CAIX) in nasopharyngeal carcinoma (NPC) tissues and their correlation with clinicopathological features and prognosis in NPC patients. The expression of HIF-1α and CAIX proteins was detected by immunohistochemical staining in 129 samples of NPC and 20 samples of chronic nasopharyngitis. The correlations between the expression of these two proteins and clinicopathological features and prognosis were evaluated in NPC patients. Our results showed that the positive expression rates of HIF-1α and CAIX proteins in NPC were significantly higher than those in chronic nasopharyngitis (both P < 0.01). In addition, high HIF-1α protein expression was correlated with lymph node metastasis and advanced clinical stage for NPC patients (both P < 0.01), whereas there were no findings of correlations between CAIX protein expression and gender, age, T stage, node involvement and clinical stage (all P > 0.05). The Spearman analysis indicated that HIF-1α was positively correlated with CAIX expression (r = 0.249, P = 0.004). HIF-1α and CAIX co-expression was associated with the poor overall survival (OS), progression-free survival (PFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) in NPC patients (P = 0.017, P = 0.022, P = 0.033, and P = 0.017, respectively). Multivariate analysis showed that the positive expression of CAIX protein was an independent prognostic factor for PFS, LRRFS and DMFS. In conclusion, overexpression of HIF-1α and CAIX might be involved in the carcinogenesis and development of NPC and they were associated with patients’ poor prognosis.

Expression and significance of hypoxia inducible factor-1α and endothelin-1 and vascular endothelial growth factor in gastrointestinal stromal tumor

Objective To investigate the expression and significance of hypoxia inducible factor-1 α (HIF-1α),endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) in gastrointestinal stromal tumor (GIST).Methods Eighty-six samples of GIST specimens were collected from Xiangya Hospital (50 cases) and Shaoyang Chinese Medicine Hospital (36 cases) from January 2003 to December 2006.The expressions of HIF-1 α,ET-1 and VEGF in the GIST were detected by immunohistochemical staininng.The relationship between HIF-1 α,ET-1 and VEGF was analyzed by using the Spearman rank correlation.The survival rates were calculated by using the Kaplan-Meier method,and the survival was analyzed using the Log-rank test.The count data were analyzed using the chi-square test.Results The expression of HIF-1α was negative in 23 cases,positive in 30 cases,strongly positive in 33 cases,and the overall positive rate was 73.3 ％ (63/86) ; the expression of ET-1 was negative in 29 cases,positive in 28 cases and strongly positive in 29 cases,and the overall positive rate was 66.3％ (57/86) ;the expression of VEGF was negative in 24 cases,positive in 26 cases,strongly positive in 36 cases,and the overall positive rate was 72.1％ (62/86).There was a positive corelation between the expressions of HIF-1 α,ET-1 and VEGF (r =0.594,0.655,0.347,P ＜ 0.05).The positive expressions of HIF-1α,ET-1 and VEGF were correlated with National Institute of Health (NIH) risk stratification,infiltration and metastasis,tumor diameter and number of nuclear division of GIST (x2=15.565,10.841,12.574,21.125; 8.171,10.002,10.354,17.317;14.710,16.230,11.116,18.886,P ＜0.05),but not with the gender,age and the initial occurring position of the tumor (x2 =0.059,O.071,5.070 ; 0.468,0.074,1.665 ; 0.231,0.370,3.712,P ＞ 0.05).The positive expression rates of HIF-1α,ET-1 and VEGF increased as the increase of the malignant level of GIST,tumor infiltration and metastasis and the tumor diameter.The follow up rate was 91.9％ (79/86),and the 3-and 5-year survival rates were 82％ and 69％,respectively.The median survival rate was 40.2 months (range,2-66 months).The 5-year survival rates of patients with positive expressions of HIF-1 α,ET-1 and VEGF were 42％,45％ and 42％,respectively,and the 5-year survival rates of patients with negative expressions of HIF-1 α,ET-1 and VEGF were 64％,65％ and 63％,respectively.The 5-year survival rates of patients with positive expressions of HIF-1 α,ET-1 and VEGF were significantly lower than those with negative expressions of HIF-1 α,ET-1 and VEGF (x2=6.325,6.124,6.287,P ＜0.05).Conclusion There is a positive correlation between the expressions of HIF-1 α,ET-1 and VEGF.HIF-1 α,ET-1 and VEGF could be served as important predictors for the prognosis of patients with GIST. Key words: Gastrointestinal stromal tumor; Hypoxia inducible factor; Endothelin-1; Vascular endothelial growth factor; Imunohistochemiscal staining

The expression and clinical significance of HIF-1α, COX-2 and E-cadherin in patients with lung adenocarcinoma

背景与目的肺腺癌发病率不断升高，而低氧诱导因子-1α（hypoxia-inducible factor-1α, HIF-1α）、环氧合酶-2（cyclooxygenase-2, COX-2）、上皮型钙粘附分子（E-cadherin）均在肿瘤细胞的分化、增殖过程中起到重要作用。本研究旨在探讨HIF-1α和COX-2、E-cadherin在肺腺癌的表达水平与患者临床病理特征之间的关系及其三者之间的内在联系。方法收集10例非肿瘤患者手术切除的正常肺组织及45例肺腺癌患者手术切除标本，应用免疫组织化学方法检测HIF-1α、COX-2、E-cadherin的表达情况。结果45例肺腺癌组织中，HIF-1α和COX-2的表达阳性率分别为60%（27/45）和40%（18/45），10例正常肺组织均未见表达。45例肺腺癌组织中E-cadherin的表达阳性率为48.9%（22/45），10例正常肺组织均见阳性表达。HIF-1α表达水平与原发肿瘤大小有密切关系（P < 0.05），但与患者年龄、吸烟与否、淋巴结转移、分化程度、术后分期无明显关系（P>0.05）。COX-2表达水平与原发肿瘤大小、淋巴结转移、术后分期、HIF-1α表达水平有密切关系（P < 0.05），但与患者年龄、吸烟与否、分化程度无明显关系（P>0.05）。E-cadherin表达水平与分化程度、淋巴结转移有密切关系（P < 0.05），但与患者年龄、吸烟与否、肿瘤最大直径、术后分期、HIF-1α的表达无明显关系（P>0.05）。结论肺腺癌组织中HIF-1α、COX-2表达增高，E-cadherin表达降低；COX-2的表达水平升高可能与HIF-1α的高表达有关，E-cadherin的表达水平与HIF-1α未发现有明显相关性。

Expression and significance of factors related to angiogenesis in choroidal melanoma.

TO INVESTIGATE EXPRESSION OF FACTORS RELATED TO ANGIOGENESIS: HIF-1α, iNOS, COX-2 and VEGF in choroidal melanoma and its clinical significance. Fifty samples of choroidal melanoma and 15 samples of melanocytic nevi of the eyelid identified by pathology were collected. Immunohistochemistry SP method was used to examine the expression of HIF-1α, iNOS, COX-2 and VEGF in these samples. The comparison among groups was done by SPSS 13.0 software. The positive expression rates of HIF-1α, iNOS, COX-2 and VEGF in choroidal melanoma group were significantly higher than those in eyelid nevi group (χ(2)=6.5542, 7.7224, 8.5828, 15.1749). The positive expression rate of VEGF was associated with the tumor size (χ(2)=10.9194), but was not associated with pathological type (χ(2)=2.0712) and the situation of scleral invasion (χ(2)=5.4289). The positive expression rate of HIF-1α was associated with the tumor size (χ(2)=7.1216) and pathological type (χ(2)=9.0889), but was not associated with the situation of scleral invasion (χ(2)=3.3586). The positive expression rate of iNOS was associated with the tumor size (χ(2)=9.5503), but was not associated with pathological type (χ(2)=1.9450) and the situation of scleral invasion (χ(2)=2.3810). The positive expression rate of COX-2 was associated with the tumor size (χ(2)=7.2970), but was not associated with pathological type (χ(2)=1.8421) and the situation of scleral invasion (χ(2)=0.4018). The expression of HIF-1α, iNOS and COX-2 were significantly associated with the expression of VEGF (r=0.9429, 1, 0.9857). The expression of COX-2 was significantly associated with the expression of iNOS (r=0.9857). The expression of HIF-1α was significantly associated with the expression of COX-2 (r=0.9857). The expression of HIF-1α was significantly associated with the expression of iNOS (r=0. 9429). The expression of HIF-1α, iNOS and COX-2 protein in choroidal melanoma were higher and may relate to angiogenesis and stimulate tumor growth. Determination of HIF-1α, iNOS and COX-2 may be helpful for the diagnosis and therapy of this tumor.