Looking for hypoxia-fingerprint in multiple myeloma and malignant melanoma patients' transcriptomic data using a binominal distribution model

Abstract Background/aim: Reduced partial oxygen pressure is a characteristic feature of many cancers. HIF-1 transcription factor, activated under hypoxic conditions, alters the gene expression profile, triggering genes, which facilitate the survival of cells in oxygen diminished environment. Importantly, the HIF-1 signaling pathway itself has been considered a potential target of anti-cancer therapy since inhibition of this pathway may significantly slow down tumor growth. Materials and methods Initially, using the in vitro hypoxic conditions we determined the set of hypoxia target genes forming the hypoxia signature for Malignant Melanoma and Multiple Myeloma cells. Subsequently, the expression profile of selected genes was tested on patients’ transcriptomic data sets using binominal distribution model. Results Based on in vitro experiment we determined the 12 hypoxia target genes forming the hypoxia signature for Malignant Melanoma and 12 hypoxia target genes for Multiple Myeloma. Importantly, 9 genes out of 12 were common for both neoplasms. The analysis of expression distribution for selected genes revealed that in Multiple Myeloma the distribution pattern follows the theoretical binominal distribution model, opposite to Malignant Melanoma, where groups of patients with high probability of active or non-active HIF-1 signaling were apparently visible. Conclusion Our analysis clearly indicates that the probability of HIF-1 pathway activation can be assessed using binominal distribution model for the selected genes forming the hypoxia signature. The model developed based on two studied neoplasms expeditiously verifies the subgroups with high and/or low probability of HIF-1 signaling in a given transcriptomic data set and allows for assessing the probability of hypoxia pathway activation or any other active signaling in tumors, at the level of individual patients.