We found that HIF-1α and LOX are highly expressed in epithelial ovarian cancer tissues, and the expression of both proteins is significantly correlated with the tumor grade, tumor diameter and lymph node metastasis.
The results showed that CCR7 expression correlated positively with HIF-1alpha and HIF-2alpha, all of them correlated with clinical stage and lymph node metastasis.
High expression of heparanase is significantly associated with dedifferentiation and lymph node metastasis in patients with pancreatic ductal adenocarcinomas and correlated to PDGFA and via HIF1a to HB-EGF and bFGF.
HIF-1α overexpression was significantly associated with larger tumor size (OR = 2.28, 95% CI = 1.49-3.50, P = 0.017), advanced TNM stage (OR = 2.29, 95% CI = 1.50-3.49, P = 0.158), and lymph node metastasis (OR = 2.05, 95% CI = 1.19-3.53, P < 0.001), but not with poor differentiation (OR = 1.21, 95% CI = 0.55-2.64, P = 0.024).
The key glycolytic transcriptional regulators (HIF-1α, p53) were analyzed in parallel to the glycolysis-related proteins, and the pooled results identified that high-level expression of HIF-1α was significantly associated with shorter overall survival (HR 0.57, 95% CI 0.42-0.79, P < 0.001) Furthermore, glycolysis-related proteins linked with poor differentiated tumors (OR 1.81, 95% CI 1.46-2.25, P < 0.001), positive lymph node metastasis (OR 2.73, 95% CI 2.16-3.46, P < 0.001), positive vascular invasion (OR 2.05, 95% CI 1.37-3.07, P < 0.001), large tumor size (OR 2.06, 95% CI 1.80-2.37, P < 0.001), advanced tumor stage (OR 1.58, 95% CI 1.19-2.09, P < 0.001), and deeper invasion (OR 2.37, 95% CI 1.93-2.91, P < 0.001).
As a result, the HIF-1alpha expression did not show a significant correlation with the clinicopathological factors, such as the depth of invasion, lymph node metastasis and tumor stage, nor patient survival in the 63 patients.
Expression of hypoxia-associated proteins was in most cases identical between primary tumours and lymph node metastases.Two cases showed strong uniform expression of CAIX and HIF1α in the primary tumour as well as in the lymph node metastases, and sequencing revealed mutations in the coding regions of the Von-Hippel–Lindau gene (VHL ).Our findings suggest that despite of the fact that MTCs have only slowly growth, tumour hypoxia plays an important role in the development of loco-regional metastases.
Although we did not find a significant correlation between the expression of HIF-1α and HIF-2α with gender, age, calcification, or Hashimoto's disease in the present study (P>0.05), both of their expressions were correlated to lymph node metastasis (P<0.05), capsular invasion (P<0.05), and TNM stage (P<0.05).
Elevated levels of HIF-1alpha protein were found in cases of breast cancer with lymph node metastasis (p=0.041), high histological grade (p=0.001) and increased Ki-67 index (p=0.031).
In addition, significant differences in HIF-1α positivity rates were observed among patients with varying tumor sizes and lymph node metastasis states (P < 0.05).
Expression of vascular endothelial growth factor D is associated with hypoxia inducible factor (HIF-1alpha) and the HIF-1alpha target gene DEC1, but not lymph node metastasis in primary human breast carcinomas.
The results revealed that HIF-1α expression was detectable in 20/60 (33.3%) of the breast carcinoma cases, and was positively associated with lymph node metastasis (P=0.007).
Of the 62 cases of CRC examined, 43 (69.4%) and 39 (62.9%) were positive for CDX2 and HIF-1alpha, respectively, such that their expression was correlated with differentiation grade, tumor stage and lymph node metastasis (chi2 test, p<0.01).
In addition, PHD2 and HIF-1α levels were correlated with lymphovascular stromal invasion (LVSI), postoperative FIGO stage, and lymph node metastasis of endometrial cancer (<i>p</i><0.05).
HIF-1alpha expression correlated with high tumour grade (P=0.009), negative oestrogen receptor (ER) status (P=0.001) and the absence of lymph node metastasis (P=0.028).
Positive staining for HIF-1alpha was observed in both pancreatic cancer and the surrounding stromal cells in more than 30% of the cases, and it significantly correlated with lymph node metastasis (P < .05).
Moreover, up-regulation of HIF-1α was significantly associated with the depth of invasion (OR = 2.49, 95 % CI = 1.28-4.83), lymph node metastasis (OR = 2.15, 95 % CI = 1.27-3.66), and vascular invasion (OR = 2.23, 95 % CI = 1.20-4.14).
FOXP1 expression was significantly correlated with the expression of HIF1 and VEGF (r=0.54, p<0.01 and r=0.37, p<0.05, respectively), but was not obviously correlated with clinical stage, lymph node metastasis and 5-year overall patient survival (p>0.05).
Moreover, exosomal miR-21 markedly enhanced snail and vimentin expression, while significantly decreasing E-cadherin levels in OSCC cells, in vitro and in vivo Finally, circulating exosomal miR-21 levels were closely associated with HIF-1α/HIF-2α expression, T stage, and lymph node metastasis in patients with OSCC.