MESOTHELIN AND EARLY DETECTION

A churchyard in the Yorkshire Dales

Note the beautiful dry-stone wall

And, of course, the beautiful Linda

 

I am plunging back into the scientific literature regarding early detection of ovarian cancer.  I am pleased to be able to boast that I understand one hell of a lot more now than I did 18 months ago, when I took my initial dip.  That is not to say that I have anything like a competent handle on the subject, nor that you should believe anything I say.  Probably what I say now should be taken with an even larger grain of salt than previously: earlier, I was afraid to conclude much of anything, because of the obvious fact that I would probably be wrong.  Now I am beginning to think that I know something I am more inclined to make judgments and even (gasp!) give advice. The original warnings still apply: I am a superannuated earth scientist, awash in an ocean of biochemistry.  Don’t trust me.

That said, I want to talk (once again) about early detection of ovarian cancer.  I believe it is commonly agreed that early detection is the best way to save lives.  There seem to be two approaches to this task: develop a symptom index (of which I have written many times before), or find a “marker” – a molecule of some kind carried by the blood (or urine) .  The symptom index has proven useful, but unfortunately symptoms usually kick in only when the cancer is in a late stage of development.  The same can be said of two protein markers that elevate along with cancer development: cancer antigen 125 (CA125) and human epididymis protein 4 (HD4).  These markers often vary in unison, with the newly validated HD4 (validated by my Hutch group) showing perhaps the greater promise.  My group (and others) has developed a way of using changes in an individual woman’s CA125 (and HD4?) levels as a more sensitive predictor.   We have also tried to use a molecule called mesothelin* as a marker, but apparently with no outstanding success.  I hope we keep on studying mesothelin.  You certainly remember Jack Andraka, the 14 year old kid who has invented a 3 cent, 5 minute test for elevated mesothelin.  Mesothelin also is known to be elevated  in ovarian cancer.  Part of the argument against screening the general population for OVCA is that its prevalence is so low that the screening would be prohibitively expensive.  If there are 25 million post-menopausal women in the United States you could screen them all every year, using Jack’s test, for $75,000.  This  is a rounding error in the fiscal burden of cancer. 

It also has been shown fairly recently that microRNAs of certain types elevate with ovarian cancer.  Micro RNAs are very short strands of the nucleic acid RNA.  They are mysterious to some extent, but one thing they do is regulate gene expression: turn genes on and off, as needed.  I have an irrational hunch that miRNAs are going to be a big player in future cancer research.  Muneesh Tewari, of whom I wrote a short time ago, is studying miRNA.

So, yes, I am trying to get serious about this cancer biochemistry stuff.  To do that,  I need to understand some basic statistical concepts.  I am going to put them in a Comment – so that you can skip them without shame or effort.  Maybe in a few days….