Background: NOTCH and hypoxia pathways are both known to be highly involved in cancer. Because of the close interplay between both of these pathways, we investigated correlation and co-expression of molecules in these pathways.
Materials and methods: In 335 unselected stage I-IIIA NSCLC patients, protein expressions of hypoxia inducible factor 1α (HIF1α), hypoxia inducible factor 2α (HIF2α), glucose transporter 1 (GLUT1), lactate dehydrogenase 5 (LDH5), carbonic anhydrase IX (CAIX), delta like 4 (DLL4), JAGGED1, NOTCH1 and NOTCH4, evaluated by immunohistochemistry, were correlated and co-expressions tested in tumor and stromal cells.
Results: HIF2α and LDH5 correlated moderately with DLL4, JAGGED1 and NOTCH4 in both tumor and stromal compartments (Spearman's r=0.16-0.33). The coexpression of HIF1α and NOTCH1 in tumor was significantly indicative of poor prognosis in univariate analysis. Hypoxia and NOTCH ligands and receptors were moderately correlated.
Conclusion: The lack of appealing coexpression findings for HIF1α and NOTCH1 may be due to the way HIF1α directly influences NOTCH signalling without depending on an elevated NOTCH expression.