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).
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-1α expression was significantly associated with tumor grade, depth of myometrial invasion, and lymph node metastasis (P = 0.014, 0.012, and 0.046, respectively).
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 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).
The results showed that compared with para-carcinoma tissue, the expression of hypoxia inducible factor 1 alpha was significantly enhanced (odds ratio = 0.122, 95% confidence interval = 0.074-0.201, p = 0.000); hypoxia inducible factor 1 alpha was associated with differentiation (odds ratio = 1.458, 95% confidence interval = 1.108-1.920, p = 0.007), T classification (odds ratio = 0.457, 95% confidence interval = 0.265-0.786, p = 0.005), lymph node metastasis (odds ratio = 0.337, 95% confidence interval = 0.185-0.614, p = 0.000), and pathological tumor-node-metastasis stage (odds ratio = 0.362, 95% confidence interval = 0.177-0.740, p = 0.005), whereas there was no relation to histological grade, lymphatic vessel invasion, blood vessel invasion, 3- to 5-year overall survival and disease-free survival.
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).
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).
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.
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).
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.
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).
HIF-1αG1790A polymorphism was found to be associated with increased risk of larger tumor size (G/G + G/A vs. A/A: OR = 1.64, 95% CI = 1.04-2.58) and borderline significant risk of lymph node metastasis (G/G + G/A vs. A/A: OR = 1.33, 95% CI = 1.00-1.78).
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.
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).
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.