Photo: Comparison of the performance of the 70 published hypoxia signatures using the IQM in 104 cancer cell lines, University of Oxford, Matteo Di Giovannantonio, Fiona Hartley
Too high demand for oxygen in the body may signal cancer. A decrease of oxygen in tissues’ micro-environment shifts metabolic pathways.
Oxygen is a substance without which there would have been no life on Earth. There are many theories supporting view that if the atmosphere compounds substantially changed their proportion we all could seek another place to live. Oxygen was this element that contributed the most to the explosion of life during the Cambrian era. At that time many species emerged on the Earth and evolution of vertebrates could start.
Finally humans appeared in over 70 percent built with water (the share decreases along with aging). Our cells, tissues, organs need oxygen to perform their tasks and continue life-processes. Oxygen subsists also in our genes what in general is an advantage when we are healthy and healthy patterns of our genetic expression are in use. But, in some cases, this expression what is more precisely signatures of selected genes may cause troubles and death. Scientists of University of Oxford in the newly published study in ,,Cell Genomics” prove that hypoxia detected remarkably early might be a predictor of cancer as it is already known its association with poor prognosis in many types of tumor across tissues. However, clinical trials to get a sufficient therapy failed, so far, mainly due to inconsistent both data and results. Why this one study fate might differ?
What is hypoxia?
Hypoxia is a very common stage of our cells building vascular network as well as present in diseases occurring in our lungs. Simply it is not enough oxygen in the tissue. That’s may be one reason of cancer within vulnerability of some genes. In the case of cancer it might be although too much demand for the substance. Why? Because cancer creates the demand proliferating defective cells at the same time making them fed with alternative vascular network. The process decreases healthy level of oxygen in normal tissue as aberrant angiogenesis fails to keep pace with increased oxygen demand. And that shifts metabolic pathways in the area with huge and often unpredictable consequences.
We investigate the performance of 70 hypoxia signatures in hypoxia vs. normal oxygen level experiments across 104 cell lines, as well as in over 5,000 clinical samples from 10 solid tumor types using 472 million length-matched random gene signatures
states Matteo Di Giovannantonio of Oxford
As scientists claim, signature and score choice strongly influenced the prediction of hypoxia in vitro and in vivo.
Oxygen concentration in genes a key for cancer?
What’s fascinating within the examined 70 signatures of genes, no individual one was found. Scientists explain this could reflect their origin in terms of the derived tissues’ response to hypoxia (different cell lines/tumor types), or this might reflect differences in the experimental conditions used (percentage of oxygen, length of time under hypoxia. One or another, frequencies of certain genes may differ and the most frequent are those that activate in a response to hypoxia. What’s more, noticed enrichment in oxygen concentration has been caught on for renal cell carcinoma. But it is not only one. There are specific signatures for breast cancer, glioblastoma or colorectal cancer cell lines. What’s more, tumor hypoxia is therefore associated with poor prognosis in tumors across tissues, including breast, bladder, brain, gastric, head and neck, liver, lung, esophageal and prostate.
Unfortunately, the case of hypoxia expression in our genes i.e. which of the variants is missing oxygen and how much is not so easy to assess. Genes expression may change, variants differ, so it isn’t easy to link it with a certain outcome. In other words our genetic base is rather instable in opposition to a fixed code nevertheless it is a code in real. The difficulties, as state Oxford scientists, do not imply it is impossible to stratify the levels of expression in line with modern technologies capacity.
The strategy could help to establish a new foundation in how to apply hypoxia signatures
says Fiona Hartley of Oxford
It could thus enhance our understanding of tumor micro-environmental biology, elucidate new pathways and biomarkers, and, ultimately, drive effective patient stratification for hypoxia modifiers and other treatment solutions – conclude scientists.
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