SYK - A New Biomarker for Early Skin Cancer Detection and Localization
Chetana Sunkari1, Zhenyu Huang2, David Alfego1, Ashani Weeraratna3, Jouni Uitto4, Andres Kriete1
Early skin cancer diagnosis - an unmet need
UV Exposure, SCC and BCC cancer
Improved Localization: Mohs Surgery
Comparison of Syk expression in human
skin with and without UV exposure
There is an unmet need to early diagnose skin damage and
presence of cancer lesions and provide a better indication of
the exact localization of lesions, which could lead to more
effective treatments.
Ratio Syk to DAPI Intensity
During Mohs micrographic surgery
the tumor margins are identified by
transformed cells and this highly
subjective method can lead to
incomplete tissue removal and
recurrence. Using Syk as a
biomarker can help to better
delineate cancerous tissue.
There is no established molecular indicator of the level of skin UV
damage, and its correlation to the onset of skin cancers. Matrix
metalloproteinases (MMPs) are well known indicators of skin
damage, but these changes are detected only after considerable
damage has been done to skin.
*
2
1
0
Normal
* p < 0.01
UV Exposed
Syk is overexpressed in UV exposed
skin. Chronic sub-erythemal UV
doses on SKH1 hairless albino mice
showed a significant increase in the
expression of Syk.
Deciphering Molecular Mechanisms
Immunofluorescence on various
tissues showed the extent to which
spleen tyrosine kinase is expressed
in them.
14
Average Syk pixels present per cell
We have indentified a new biomarker to diagnose skin cancer.
Spleen tyrosine kinase (Syk) is upstream of matrix metalloproteinases in the signal transduction pathway. There is a
significantly higher expression of spleen tyrosine kinase in different
skin cancer types as compared to control tissue.
3
12
Expression of Syk in
SCCs and BCCs
compared to normal
skin (human biopsies
from the same patient).
10
8
6
4
2
0
Human Skin Biopsies
Skin Cancer Types
Future Work: Role of Syk in Melanomas
Skin Cancers make 50% of all cancers, 1 million new cases/year
Basal Cell Carcinomas (BCC) – 80% of new skin cancers
Squamous Cell Carcinomas (SCC) – 16% of new cases
Melanomas – 4%, but most deadly
UV radiation activates Syk, which is upstream of a
signaling cascade including the tumor marker MMP-1.
PCR performed on
melanoma cell lines that
Syk correlates to the
invasiveness on the cell
line. More invasive the cell
line, less expression of Syk.
1E+16
1E+14
Invasiveness
1E+12
1E+10
00000000
1000000
10000
100
1
Project Milestones and Goals
Early Detection
10 weeks
5 weeks
Linear (10 weeks)
 UV exposure increases Syk expression in vitro as well as in vivo.
 Changes in Syk precedes MMP-1 expression, it can serve as an early
marker for cancer lesions.
 Syk is overexpressed in skin cancers including SCC, BCC and
Melanoma, compared to normal skin.
 To establish a device and procedure to use Syk as a diagnostic marker in
vivo.
 To investigate the merit of spleen tyrosine kinase as a means of delaying
progression or curing skin cancers.
Linear (5 weeks)
140
y = 1.609x - 2.5708
120
MMP-13 expression
100
80
y = 0.2681x + 17.027
60
40
20
0
0
-20
20
40
60
80
100
120
140
Less invasive melanoma WM 35
More invasive melanoma 1205Lu
Affiliations
160
Syk Expression
We found Syk to be increased at the end of week 5 after UV
radiation, whereas MMPs do not show a significant increase until
week 10. For these experiments we developed and applied a solar
radiator in a mouse model.
Acknowledgements



W.H. Coulter Foundation
NetScientific Group
Hebrew University /Jerusalem - Drexel University Partnership program
Coulter-Drexel Translational Research Partnership Program
1) School of Biomedical Engineering, Science and Health Systems,
Drexel University
2) University of Pennsylvania
3) Wistar Institute, Tumor Microenvironment and Metastasis Program
4) Thomas Jefferson University, Dept. of Dermatology and
Subcutaneus Biology