Liquid Biopsy for Cancer Metasis Detections Lesson
Notes
- a metastatic tumor is the same type as the original cancer
- ex.) if colon cancer metastasizes, it will still be colon cancer just in the liver
- Steps
- local invasion
- intravasation (entry into blood or lymph vessels)
- circulations
- extravasation
- colonisation
- most tumors are epithelial original
- mutate and then become cancer
- how do you detect metastasis?
- through imaging like CT scan or MRI
- the existance of circulating tumor cells was introduced a long time ago, but they didn’t have the technonology to detect it
- nanotechnology might be credited for the resurgance of interest in CTCs
- 1900s-2000
- in 2004, the cell search system was the first FDA cleared test for enumerating CTCs in metastatic breast, prostate, and colorectal cancer
- first and only clinically validated, FDA -cleared blood test for enumerating CTCs
- nanotechnology might be credited for the resurgance of interest in CTCs
- How does CellSearch work?
- have an EpCAM marker and use an antibody that responds to the epCAM molecule and will will use a magnet to attract the antibodies and in turn the EpCAM molecules
- Immunomagnetic seperation using anti-EpCAM ferrofluids
- need to then double check and use fluorescence staining and identifications
- DAPI for Nucleus
- Cytoskeleton (CK+)
- need to check it has it and it has to be positive to confirm its a CTC
- CD45 for leukocytes
- to make sure its not a WBC
- have an EpCAM marker and use an antibody that responds to the epCAM molecule and will will use a magnet to attract the antibodies and in turn the EpCAM molecules
- what is in blood?
- red blood cells (4.5-6 million per mL)
- no nucleus
- carry oxygen
- white blood cells (4,000-11,000 per mL)
- does have a nucleus and are immune defense
- diverse types
- larger than RBC
- platetlets (150k-450k per mL)
- no nucleus
- blood clotting
- cell fragments
- CTCs (only present in cancer patients and only or less than 10 per mL)
- has nucleus
- cell origin usually from epithelial cell
- larger than a RBC but comparable to a WBC
- red blood cells (4.5-6 million per mL)
- How does enumerating the numebr of CTCs help?
- would keep checking and used the Kaplan-Mieyer plot for overall survival for enrolled patienrs
- patients with less than 5 CTCs overall survival is 21.9 months
- patiens with over CTCs have an overall survival of 10.9 months
- the number of CTCs inpact the overall survival
- would keep checking and used the Kaplan-Mieyer plot for overall survival for enrolled patienrs
- liquid biopsy= test done on a sample of blood (or sometimes other fluids like urine or cerebrospinal fluid) to detect diseases
- liquid biopsy in the future may be able to (especially if you combine it with big data)
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transforming cancer detection and monitoring
Today in class, we used TCGA data from the UCSC Xena database to generate Kaplan-Meier survival plots which are plots that utilize a statistical method used to estimate the survival function from lifetime data showing the proportion of patients surviving over time after diagnosis or treatment (the curve represents the survival probability at different time points). I focused on two cancer types: breast cancer (TCGA BRCA) and acute myeloid leukemia (TCGA LAML), and using the overall survival data, we plotted the probability of survival over time for each cancer type. In the plot for breast cancer, we see a gradual decline in survival probability, with many patients surviving well beyond 4,000 days, but for the plot for acute myeloid leukemia, it showed a much steeper drop meaning a significantly lower survival rate and shorter survival times
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