《自然》近日发表的一篇研究论文发现借助游离RNA有望在症状出现之前发现孕妇是否患有先兆子痫（编者注：先兆子痫是一种在怀孕20周后可能会出现的常见妊娠期高血压疾病，是导致孕产妇死亡的第二大原因，健康女性有时会在没有任何先兆的情况下患上此病），Nick就这一发现采访了该篇论文的通讯作者——来自美国斯坦福大学的Stephen Quake。欢迎收听本期播客剪辑，了解更多精彩内容。也欢迎前往iTunes或你喜欢的其他播客平台下载完整版，随时随地收听一周科研新鲜事🎧。
音频文本：
First up on the show: pre-eclampsia. This is an extremely serious condition that can occur during pregnancy, characterised by high blood pressure. In severe cases, it can lead to kidney dysfunction, seizures and even death. Early detection of pre-eclampsia would give pregnant people more options for treatment, and a new study aims to allow just that – detecting pre-eclampsia earlier with just a simple blood test. I called up one of the authors, Stephen Quake, to find out more, and I started by asking how many people this disorder affects.
Interviewee: Stephen Quake
Pre-eclampsia is a very common disease in pregnancy, and it’s the cause of something like 14% of maternal deaths each year globally and it’s the second leading cause of maternal death. The costs are enormous. In the US it’s something like US$2 billion a year in care. It’s a very common thing and it’s something that is preventable if we’re able to be diagnosed earlier.
Interviewer: Nick Petrić Howe
And how is it currently diagnosed and at what point will people find out that they have this?
Interviewee: Stephen Quake
So, pre-eclampsia is a hypertensive disease, so high blood pressure, hypertension, and so today it’s mostly diagnosed when you have that high blood pressure and you’re already feeling the symptoms of the disease. So, when you’re symptomatic is when it’s diagnosed. Our work was aimed at finding ways to predict who is going to get it before you have high blood pressure and hypertension.
Interviewer: Nick Petrić Howe
And so you mention there you were looking at different ways to detect this, looking for non-invasive methods, so what were you looking for?
Interviewee: Stephen Quake
So, we’re using a phenomenon called cell-free RNA. So, it turns out that every tissue in your body contributes RNA into the blood, and when you’re pregnant it’s coming from the placenta and fetus as well as all the maternal tissues, and RNA is the cells’ way of expressing proteins. It’s that intermediate step. When it wants to express a protein, the gene is transcribed from the genome, it’s copied into RNA and then the RNA is used as a template to make the protein. So, it’s really a very valuable measure of what the cells are doing at any given point in time.
Interviewer: Nick Petrić Howe
And so, this RNA, is it just floating around the body waiting to be picked up?
Interviewee: Stephen Quake
It is floating around the body, and much of it gets digested, but some of it survives and circulates through the blood, and that’s the little bit that we analyse.
Interviewer: Nick Petrić Howe
And what could that tell us about pre-eclampsia?
Interviewee: Stephen Quake
Because the body is changing due to disease, hypertension is happening and high blood pressure is happening and that’s going to cause changes, and even before those symptoms are manifested, the changes are happening in the tissues, and so the RNA is changing because the cells are either causing the disease or responding to it, and it’s those messages that we’re analysing and that are providing the earliest signals of disease.
Interviewer: Nick Petrić Howe
So, in this study, you did a clinical trial of 199 people and you had 404 blood samples from them. What were you able to find from this and what were the sort of markers of pre-eclampsia?
Interviewee: Stephen Quake
What we found was roughly 500 genes whose expression levels change through the course of pregnancy in the women who had pre-eclampsia versus those who didn’t. We analysed them to try to understand which cell types they came from and what was kind of the underlying biology to be able to learn something about that and particularly cells of the immune system, neuromuscular cells, endothelial cells, and relate that to the sort of biological cause of pre-eclampsia. And then we also found a subset of those genes that would predict who would get pre-eclampsia before the symptoms manifested, and so we think that panel of genes could form the basis of a diagnostic screen to help understand who is at risk. Now, it must be said that this is all still very early and to really understand if there’s going to be clinical value, a large, blinded trial has to be done. But I think it’s an exciting proof of principle that indicates what might be possible in the field.
Interviewer: Nick Petrić Howe
And at what point does pre-eclampsia typically occur and then at what point were you able to detect the changes that indicated that pre-eclampsia was a risk?
Interviewee: Stephen Quake
So, often the onset is in middle to late pregnancy, and formally they would say after 20 weeks of gestation they are on the lookout for it. In our case, we were seeing signals as early as 12 weeks.
Interviewer: Nick Petrić Howe
And there were these changes that you detected. Sometimes gene expression changes, RNA changes can be quite subtle. Were they quite clear? Were they quite distinct between people who developed pre-eclampsia and people who didn’t?
Interviewee: Stephen Quake
Yes, these were really quite distinct, and we were happy that we were able to replicate them on other cohorts, and so it was something that has us very comfortable, I think with the rigour of the analysis and the reproducibility of the effect.
Interviewer: Nick Petrić Howe
What was the sort of diversity of the people involved? Do you think this was a representative sample? Would these changes in gene expression occur in the majority of people who were pregnant, or how representative do you think this group was?
Interviewee: Stephen Quake
Yeah, that’s a really interesting question, and it’s one that has been an open question in the field of cell-free RNA for a number of years because it’s such a young field. We went out of our way to recruit a fairly diverse cohort here, and one of the really amazing things about the study was that in our validation cohort, we had some ethnicities that weren’t represented in the discovery cohort and the results held for them. And so, both on the basis of the diversity of the cohort and the fact that the validation cohort was even more diverse, we’re feeling pretty good about that.
Interviewer: Nick Petrić Howe
So, you had a diverse group of people to begin with when you were just looking for these signatures of pre-eclampsia, but then when you went to validate this with another group of people to see if those markers were there again, it was an even more diverse group of people. So, taking this altogether, what do you think the implications of this study are?
Interviewee: Stephen Quake
Well, I mean, we’re hoping it’s going to form the basis of a test that’s going to save a lot of lives going forward. This is all about trying to improve healthcare for expectant mothers and their unborn babies, and pregnancy shouldn’t be a thing that has fatalities associated with it, and I hope this work can contribute to realising that vision of eliminating deaths during pregnancy.
Interviewer: Nick Petrić Howe
That was Stephen Quake from Stanford University and also the Chan Zuckerberg Biohub, both in the US. For more on this study, check out the paper in the show notes.
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