Stesura Seveso


Archivio Italiano di Urologia e Andrologia 2021; 93, 2148

ORIGINAL PAPER

No conflict of interest declared.

INTRODUCTION
According to the GLOBOCAN data, bladder cancer (BC)
is the 7th most commonly diagnosed cancer in men and
it declines to 11th worldwide, when both sexes are con-
sidered (1). Worldwide age-standardized mortality rate
has been reported as 3.2 for men vs. 0.9 for women per
100.000 persons, however incidence and mortality rates
vary depending on the healthcare systems, management
protocols and development level of the countries. 
The most common subtype of BC is urothelial carcinoma
(UC) and the molecular mechanism of UC is not com-
pletely understood as in other cancers (2). 
Receptor tyrosine kinases (RTKs) play key roles in cellular
signal transduction and they are one of the most com-
mon types of molecules investigated for this purpose. In
humans, 20 distinct subfamilies of RTKs exist that are
categorized according to their aminoacid sequence iden-
tities and structural similarities in their extracellular
regions (3). One of these is the subfamily of TAM recep-
tors comprising Sky (Tyro3), Axl, and Mer. They partic-
ipate in a signaling axis where growth arrest-specific 6
(Gas6) protein is a ligand (4). The oncogenic nature of
Axl, Sky and Mer is demonstrated through activation of
signaling pathways involved in proliferation, migration,
invasion, angiogenesis, inhibition of apoptosis, and ther-
apeutic resistance (5). It has been shown that overex-
pression of Axl, Sky, Mer RTKs, and their ligand Gas6 is
associated with poor prognosis in various types of
tumors (6). The close relationship with the  pathogene-
sis of many cancers suggests that Gas6 and its TAM
receptors could be potential biomarkers and targets for
treatment (7).
The molecular biology of BC is complex and not fully
understood. There is a very limited number of studies
investigating the relationship between BC and
Gas6/TAM receptors. Yeh et al. investigated the role of
Axl in the pathogenesis of locally advanced and metasta-
tic BC patients (8). They indicated that c-Met and its
crosstalk with Axl could contribute to the progression of

Objectives: It has been shown that the dys-
regulation of tyrosine kinase Axl receptor

and its ligand growth arrest-specific gene (Gas6) are associated
with poor prognosis in various types of tumors but there is not
enough study about their importance in bladder cancer (BC). 
We evaluated the relation of Gas6 gene expression and tyro-
sine-kinase Axl and Sky (Tyro 3) receptors with tumor stage
and grade in patients with BC. 
Material and Methods: The study group consists of 55 patients
whose transurethral resection of bladder (TUR-B) has been
performed due to BC and the control group consists of 12
patients with normal bladder mucosa. In tissues mRNAs of
Gas6, Axl, and Sky receptors were examined by quantitative
(Real-Time) PCR (qPCR). Protein expression was measured by
immunohistochemistry. Plasma Gas6 protein levels were com-
pared with control group by ELISA method.
Results: Patients with BC were grouped as Ta low (n=17), 
Ta high (n=5), T1 low (n=9), T1 high (n=8) and T2 (n=16)
according to their TUR-B pathologies. The qPCR analysis
showed that the expression of Gas6 gene and Axl receptor is
higher in the tumor-positive group and the immune-histochemi-
cal showed that the bladder samples of the tumor-positive
group stained significantly positive. When the patients are
grouped according to the TUR-B pathologies, a statistical sig-
nificant difference was observed among groups in the qPCR
analysis ratios of Gas6 gene and Axl receptor by (p < 0.05) but
no significance was found for Sky receptor (p > 0.05). When
Gas6 protein levels in plasma samples were compared by
ELISA method, a statistical significance was determined among
groups (p = 0.001). 
Conclusions: Our findings indicate that mRNAs of Gas6 and
Axl receptor are closely related to tumor stage and grade in
patients with BC. Further studies are needed for understanding
the role of Gas6 and its receptors on the neoplastic transforma-
tion in terms of novel biomarkers and potential therapeutic
 targets.

KEY WORDS: Bladder cancer; Gas6; Axl; Sky; Tyro3.

Submitted 31 March 2021; Accepted 17 May 2021  

Gas6 expression and Tyrosine kinase Axl Sky receptors:
Their relation with tumor stage and grade in patients 
with bladder cancer

Murat Akgül 1, Özgür Baykan 2, Zeynep Çağman 3, Mustafa Özyürek 4, İlker Tinay 5, Cem Akbal 6, 
Fikriye Uras 7, Levent Türkeri 6

1 Department of Urology, Tekirdag Namık Kemal University Medical School, Tekirdağ, Turkey;
2 Department of Biochemistry, Balıkesir University Medical School, Balıkesir, Turkey;
3 Department of Biochemistry, Bezmialem University, School of Pharmacy, Istanbul, Turkey;
4 Department of Physiology, Marmara University, School of Medicine, Istanbul, Turkey;
5 Anadolu Medical Center, Gebze, Kocaeli,Turkey;
6 Department of Urology, Acıbadem University, School of Medicine, Istanbul, Turkey;
7 Department of Biochemistry, Marmara University, School of Pharmacy, Istanbul, Turkey. 

DOI: 10.4081/aiua.2021.2.148

Summary



149Archivio Italiano di Urologia e Andrologia 2021; 93, 2

Gas6 and Axl Sky receptors’ relation with bladder cancer

human BC. Rui et al. investigated the relationship
between long noncoding RNA and BC (9). They showed
that GAS6-AS2, a long noncoding RNA, was significant-
ly up-regulated in BC tissues and positively correlated
with tumour stages and poor prognosis. Identification of
new prognostic markers and therapeutic targets for BC is
urgently required. In the present study, we aimed to elu-
cidate the relation between Axl/Sky/Mer RTKs and its lig-
and Gas6 in patients with UC of bladder.

MATERIALS AND METHODS
The sample size was calculated based on the formula
according to the previously published studies (6, 8). Our
study group includes 55 patients with transurethral
resection of bladder tumor, where the histopathological
diagnosis of the tumors was UC. The control group con-
sists of the 12 patients whom bladder mucosa has been
biopsied during radical prostatectomy operation. Tissues
from bladder tumor or mucosa were stored at -80 °C. 
In this study, mRNA expression of Axl, Sky, and Gas6 in
the tissues was analyzed by quantitative (real-time) poly-
merase chain reaction (qPCR). Protein expression of Gas6,
Axl, and Sky was analyzed by immunohistochemistry.
Plasma and urine samples of patients were collected
before transurethral resection and Enzyme linked
Immunosorbent Assay (ELISA) was used to measure Gas6
protein level. Plasma and urine samples of a control
group, who are older than 40 years of age and without
any history of malignancy, has been used for compari-
son. The urine and venous plasma aliquots were stored
at -80°C before analysis after centrifugation at 2300 g for
15 min at room temperature.  
The study has been approved by the local institutional
ethics committee (Approval number: 09.2012.0087) and
conducted in conformity with the Declaration of
Helsinki in 1995. Written informed consent were
obtained from all patients included in the study.

Real-time PCR (qPCR) 
Total RNA was isolated using TriPure isolation reagent
solution (Roche, Mannheim, Germany) according to the
manufacturer's instructions. The mRNA expression of
the Gas6, Axl and Sky were determined using specific
primer sequences.

Specific primer sequences used for the Gas6 gene: 
• 5’-TGCTGTCATGAAAATCGCGG-3’ (gas6-5’; 1328-
1347) 

• 5’ CATGTAGTCCAGGCTGTAGA-3’ (gas6-3’; 1594-
1613)

Specific primer sequences used for the Axl receptor gene:
• 5’-GGTGGCTGTGAAGACGATGA-3’ (Axl-5’; 1820-
1839) 

• 5’ CTCAGATACTCCATGCCACT-3’ (Axl-3’; 2103-
2122) 

Specific primer sequences used for the Sky receptor
gene:
• 5’-CACTGAGCTGGCTGACTAAGCCCC-3’(Sky-5’;
2719-2742)

• 5’-AATGCATGCACTTAAGCAGCAGGG-3’(Sky-3’;
3039-3062)

The qPCR analysis was performed using SYBR Green dye
(Light Cycler-RNA Amplification Kit SYBR Green I; Roche,
Mannheim, Germany).  Target gene expression was deter-
mined by comparing the amount of threshold loop with
the glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
gene.

Immunohistochemical analysis
Streptavidin biotin peroxidase immunohistochemical
staining method was applied to show the immune expres-
sion of Gas6 protein and Axl, Sky receptors proteins in
paraffin-embedded tissues. The immune expression posi-
tivity in BC tissue was observed as cytoplasmic staining.
According to the intensity of staining, it was scored as
0 (Figure 1A), +1 (Figure 1b), +2 (Figure 1c), +3 (Figure
1d). Immunohistochemistry expression index was
obtained by multiplying the cytoplasmic staining density
and the ratio of stained cells. Two authors, who were
blinded to the clinical course of the patients, independ-
ently evaluated immunoreactivity, and the average count-
ed by these two authors was used for statistical analyses. 

ELISA method
The human GAS6 sandwich ELISA development kit
(R&D Systems, Inc., Minneapolis, MN, USA) and a
Substrate Reagent Pack (Color reagent A&B) (R&D
Systems, Inc.) were used to measure plasma GAS6 levels.
Our group has been optimized the development kit to
measure human plasma GAS6 levels and established ref-
erence intervals (10). Briefly, the following parameters
were tested for optimization: type of antibody; capture
antibody concentration; dilution solution; dilution ratio
of samples and calibrators; blocking agent (BSA or non-
fat dry milk), and incubation time and temperature.
Dilution solution for samples and calibrators was PBST
containing 1 mM EDTA and 1% BSA. Dilution ratio of
samples and calibrators was 1/40. Incubation time dur-
ing antigen antibody interaction (both capture and
detection antibodies) was 1h at 37°C. After analytical
validation studies of the method, samples were analyzed.

Figure 1. 
The cytoplasmic staining of immune expression for Gas6
protein and Axl, Sky receptors proteins positivity in BC tissue.
According to the intensity of staining, it was scored as 
1A: 0, 1B: +1, 1C: +2, 1D: +3. 



Archivio Italiano di Urologia e Andrologia 2021; 93, 2

M. Akgül, Ö. Baykan, Z. Çağman, M. Özyürek, İlker Tinay, C. Akbal, F. Uras, L. Türkeri

150

Statistical analysis
In descriptive statistics of the data, frequency, ratio,
mean and standard deviation values were used. 
The distribution of data was tested with Kolmogorov-
Smirnov. Student t test and ANOVA were used to ana-
lyze the parametric section data. Mann-Whitney U and
Kruskal-Wallis tests were used for the analysis of non-
parametric data. SPSS 15.0 software (SPSS, USA) was
used in the analysis.

RESULTS

Patient demographics
The BC patients were grouped according to their patho-
logical degrees and stages: Ta low grade (n=16), Ta high
grade (n=5), T1 low grade (n=10), T1 high grade (n=10),
T2 high grade (n=14) and normal bladder mucosa con-
trol group (n=12). Mean ages of the patients with BC and
the control group were 62.8 ±10.7 and 57.3 ± 7.0 years,
respectively (p > 0.05). Patients with BC, were male in
81.8% and female in 18.2%, while the control group
consisted of male patients.

Tissue analyses
The qPCR results showed that the mRNA expression of
Gas6 and Axl receptor were higher in the tumor-positive
patient group, where Sky receptor gene were higher in
control group, these differences were not significant
(p > 0.05) (Table 1). When the patients are grouped
according to the grade and stage, significant differences
were observed for Gas6 and Axl receptor genes
(p < 0.05). But no significant difference was found for
Sky receptor (p > 0.05) by qPCR (Figure 2). 

The immunohistochemical expression index for the
Gas6 and Axl receptor were statistically higher compared
to the control group (p < 0.05). The immunohistochem-
ical expression index of Gas6 protein, Axl, Sky receptors
for BC and control group is shown in Table 2. 

Plasma and urine analyses
The mean plasma Gas6 protein levels for the control
group and the BC patient group were 6.5 ± 2.6 ng/mL
and 9.9 ± 2.4 ng/mL, respectively (p < 0.001). The dis-
tribution according to the stage and the grade of the
patients are shown in Figure 3. Gas6 protein was not
detected in urine samples by ELISA.

DISCUSSION
In the present study, an association between BC and
expression of Gas6, Axl and Sky was identified using
three different methods: qPCR and immunohistochem-
istry in tissues and Gas6 levels in plasma by ELISA. 
The qPCR analysis showed that mRNA expression of
Gas6 and Axl are higher in the BC group than the con-
trol group but not significantly (p > 0.05). mRNAs of
Gas6 and Axl was higher in Ta high grade and T1 low
grade significantly, but gradually decreasing in T1 high
grade and T2 stages. Using the immunohistochemical
examination, the BC group showed significantly higher
(p < 0.05) Gas6 and Axl receptor expression compared
to the control group. ELISA analysis showed higher Gas6
protein levels in plasma of the BC group compared to the
control group (p=0.001), where highest levels are detect-
ed in patients with T2 tumors.

Table 1. 
Gas6, Axl, Sky receptor gene expression copy level assessed
by the qPCR method.

Control group Tumor-positive patient group p
n Median Min. Max. n Median Min. Max.

Gas6 11 60.6 7 294 50 73.1 10 1810 0.223*

Axl 12 288.7 145 578 55 421.5 87 1997 0.288*

Sky 11 10000 2888 15497 54 8048 1591 31333 0.588*

* Mann Whitney U test.

Table 2. 
Immunohistochemical expression index of Gas6 protein, Axl,
Sky receptors for BC and control group.

Figure 2. 
Expression of Gas6 and Axl receptor mRNAs in BC against
tumor stage and grade by qPCR.

Figure 3. 
Gas6 protein levels in plasma samples according to the stage
and the grade of the BC patients with ELISA analysis.

Control group Tumor-positive patient group p
n Median Min. Max. n Median Min. Max.

Gas6 6 5 0 90 32 85 0 300 0.006

Axl 6 15 0 70 28 60 10 200 0.037

Sky 6 50 0 200 32 180 0 300 0.261



151Archivio Italiano di Urologia e Andrologia 2021; 93, 2

Gas6 and Axl Sky receptors’ relation with bladder cancer

The definitive diagnosis of BC ultimately depends on cys-
toscopic examination of the bladder, which is an invasive
method. There are continuous efforts for the development
of non-invasive reliable tumor markers to facilitate the
diagnosis. However, none of these markers have been
accepted for the diagnosis or follow-up in routine practice
(11). By the help of further studies, the Gas6/Axl axis may
represent an attractive diagnostic tool for BC. Relationship
between various physiological events and Gas6, and/or its
receptors has been demonstrated, however, its exact
mechanism has not been elucidated yet (12, 13).  The rela-
tionship between Gas6 and/or its receptors with tumor
suppressor genes such as Inositol polyphosphate-4-phos-
phatase (INPP4B) remains uncertain (14). The Gas6 gene
and particularly the Axl receptor are highly overexpressed
in many diseases. Numerous biological dysfunctions,
inflammatory diseases and autoimmune disorders are
related to the overexpression of Gas6 and its receptors (6).
They also participate in the development, progression and
metastatization of a range of malignancies (15). Prostate
cancer, breast cancer, lung cancer, leukaemia and cancers
of gastrointestinal tract including colon are the most stud-
ied malignancies (5, 6, 16). Recent studies have also
demonstrated an important role of AXL signaling in tumor
proliferation, survival, stem cell phenotype, prognosis,
metastasis, and resistance to cancer therapy (16).
However, there is an opposite situation in renal cell carci-
noma, which is a urogenital tumor where the Gas6 and
Axl-Sky receptors are associated with good prognosis (17).
When we look at the stage and grade of BC, it seems that
mRNAs of Gas6 and Axl receptor are very close to each
other in the control and Ta low grade group. 
The malignant potential of low-grade BC, that was for-
merly regarded as 'low malignant potential papillary
urothelial neoplasia', may be related to different molecu-
lar pathological and histopathological features. In this
respect, it is similar to the new WHO-ISUP classification
(18). In the present study, the expression of Gas6 was
higher at Ta high grade and T1 low grade, but differen-
tiation was gradually decreasing at T1 high grade and T2
stages. Similarly, in the study of Sun et al., the gene
expression of Gas6 and Axl receptor was found to be
higher in G1 endometrial cancer, however, it was gradu-
ally decreasing in G2 and G3 endometrial cancers where
the differentiation is poor (19).
Using the immunohistochemical examination, Gas6 and
Axl receptor were found to have a significantly higher
protein expression at BC compared to the control group.
However, similarly to Sky receptor qPCR results, there
was no statistically significant difference between the BC
and the control group. Using immunohistochemistry
examination, Hattori et al. investigated the relationship
between increased expression of the Axl/Gas6 signal cas-
cade and prognosis of patients with upper tract urothe-
lial carcinoma. They concluded that the protein expres-
sion of Axl and its ligand Gas6 is related to worse clini-
cal outcome in upper tract urothelial tumors (20).
The plasma levels of Gas6 protein measured by ELISA
were significantly higher in the BC group compared to the
control group. In addition, mean levels of Gas6 protein in
plasma were significantly higher in T2 patients compared
to other groups. This may be important for the separation

of the muscle invasive BC from non-muscle invasive BC.
Therapeutic potential of AXL inhibition has been
explored for cancer therapy (21). A variety of AXL
inhibitors have been developed and are efficacious in
preclinical studies. These agents offer new opportunities
for therapeutic intervention in the prevention and treat-
ment of advanced disease. For the treatment of the breast
cancers, BGB324 (R428) and SGI7079, which are the
highly selective Axl tyrosine kinase inhibitors, entered in
clinical studies (22, 23).  Mao et al. showed that GAS6
was overexpressed in BC cells. They also found that high
levels of GAS6 expression were related to tumor stage,
grade, and poor overall survival (24). Unfortunately,
there are no enough clinical studies on anti-Axl/Gas6
therapy focusing on BC. However, in light of the future
studies, this pathway could be a candidate as novel bio-
marker and as an approach for treatment for BC. 

Limitations of the study
This hypothesis-generating study and our results have
some limitations such as small sample size. The control
group consists of the normal bladder tissues of the
prostate cancer patients is another limitation of the
study. Normal bladder tissue is excised as a standard sur-
gical procedure during radical prostatectomy operations.
We preferred to use this normal bladder tissue as a con-
trol group without an ethical restriction. We could not
excise the normal bladder tissue from healthy individu-
als as a control group because of the ethical problems. 
Gas6 and its ligands might represent an attractive diag-
nostic tool in the future. However, expression of these
proteins was studied in tissues requiring an invasive
biopsy to be obtained. On the other hand, plasma Gas6
ELISA results were also promising for BC diagnosis and
could be used as non-invasive diagnostic test. Of course,
future studies with larger sample size will provide more
reliable information for implementation of plasma Gas6
test as a biomarker.  ELISA method was used to detect
the urine Gas6 protein levels but Gas6 protein was not
detected in urine samples. The sensitivity of this method
may not be appropriate for determining the level of Gas6
protein in urine samples. Gas6 protein could make a
complex with soluble form of Axl (25). Further studies
for optimization of plasma Gas6 ELISA method for meas-
urement of Gas6 in urine samples are necessary.

CONCLUSIONS
We evaluated the relationship between Gas6/RTKs and
BC with three different methods by performing qPCR
analysis, immunohistochemistry and ELISA analysis.
Our findings indicate that mRNAs of Gas6 and Axl
receptor are closely related to tumor stage and grade in
patients with BC. Further studies are needed for under-
standing the role of Gas6 and its TAM receptors on the
neoplastic transformation in terms of novel biomarkers
and potential therapeutic targets.

ACKNOWLEDGMENTS
This study was supported by Marmara University Scientific
Research Projects Committee (Grant number: SAG-C-TUP-
130612-0208).



Archivio Italiano di Urologia e Andrologia 2021; 93, 2

M. Akgül, Ö. Baykan, Z. Çağman, M. Özyürek, İlker Tinay, C. Akbal, F. Uras, L. Türkeri

152

REFERENCES
1. Antoni S, Ferlay J, Soerjomataram I, et al. Bladder cancer inci-
dence and mortality: A global overview and recent trends. Eur Urol.
2017; 71:96.

2. Kates M, Bivalacqua TJ. Non-muscle invasive bladder cancer.
Campell-Walsh Urology 12th edition Elsevier Saunders Press 2020;
135:14115.

3. Robinson DR, Wu YM, Lin SF. The protein tyrosine kinase fami-
ly of the human genome. Oncogene 2000; 19:5548-57.

4. Hafizi S, Dahlbäck B. Gas6 and protein S. The FEBS Journal.
2006; 273:5231 44.

5. Brown M, Black JR, Sharma R, et al. Gene of the month:Axl. J
Clin Path. 2016; 69:391.

6. Paccez JD, Vogelsang M, Parker MI, et al. The receptor tyrosine
kinase Axl in cancer: biological functions and therapeutic implica-
tions. Int J Cancer. 2014; 134:1024.

7. Wu G, Ma Z, Cheng Y, et al. Targeting Gas6 / TAM in cancer
cells and tumor microenvironment. Mol Cancer. 2018; 17:20.

8. Yeh CY, Shin SM, Yeh HH, et al. Transcriptional activation of the
Axl and PDGFR-a by c-Met through a ras-and Src-independent
mechanism in human bladder cancer. BMC cancer. 2011; 11:139.

9. Rui X, Wang L, Pan H, et al. Lnc RNA GAS6-AS 2 promotes
bladder cancer proliferation and metastasis via GAS6-AS 2/miR-
298/CDK 9 axis. J Cell Mol Med. 2019; 23:865-876.

10.  Cagman Z, Bingol Ozakpinar O, Cirakli Z, et al. Reference
intervals for growth arrest-specific 6 protein in adults. Scand J Clin
Lab Invest. 2017;77:109-114. 

11. Babjuk M, Burger M, Comperat E, et al. European Association
of Urology on non muscle invasive bladder cancer. EAU Guidelines.
2020; 4:8.

12. Eksi Alp E, Altinkaya N, Cagman Z, et al. Plasma growth
arrest-specific 6 levels in term and preterm newborns. J Mat-Fet
Neo Med. 2018; 31:1151.

13. Uras F, Küçük B, Özakpınar ÖB, et al. Growth Arrest-Specific
6 (Gas6) and TAM receptors in mouse platelets. Turk J Hemat.
2015; 32:58.

14. Lopez SM, Hodgson MC, Packianathan C, et al. Determinants
of the tumor suppressor INPP4B protein and lipid phosphatase
activities. Bioch Biophy Res Comm. 2013; 440:277.

15. Zhang S, Xu XS, Yang JX, et al. The prognostic role of Gas6 /
Axl axis in solid malignancies: a meta-analysis and literature
review. Oncotargets and Therapy. 2018; 11:509.

16. Rankin E, Giaccia A. The receptor tyrosine kinase AXL in can-
cer progression. Cancers. 2016; 8:103.

17. Gustafsson A, Martuszewska D, Johansson M, et al. Differential
expression of Axl and Gas6 in renal cell carcinoma reflecting tumor
advancement and survival. Clin Cancer Res. 2009; 15:4742.

18. Sauter G, Algaba F, Amin M, et al. Tumors of the urinary sys-
tem: non-invasive urothelial neoplasias. In: Eble JN, Sauter G,
Epstein Jl, Sesterhenn I, eds. WHO classification of classification of
tumors of the urinary system and male genital organs. Lyon: IARCC
Press 2004; 29.

19. Sun WS, Fujimoto J, Tamaya T. Coexpression of growth arrest-
specific gene 6 and receptor tyrosine kinases Axl and Sky in human
uterine endometrial cancers. Ann of Onco. 2003; 14:898.

20. Hattori S, Kikuchi E, Kosaka T, et al. Relationship between
increased expression of the Axl/Gas6 signal cascade and prognosis

of patients with upper tract urothelial carcinoma. Ann Surg Oncol.
2016; 23:663.

21. Wu X, Liu X, Koul S, et al. AXL kinase as a novel target for can-
cer therapy. Oncotarget. 2014; 5:9546.

22. Holland SJ, Pan A, Franci C, et al. R428, a selective small mol-
ecule inhibitor of Axl kinase, blocks tumor spread and prolongs sur-
vival in models of metastatic breast cancer. Canc Res. 2010;
70:1544.

23. Wang X, Saso H, Iwamoto T, et al. TIG1 promotes the develop-
ment and progression of inflammatory breast cancer through acti-
vation of Axl kinase. Cancer Res. 2013; 73:6516.

24. Mao S, Wu Y, Wang R, et al. Overexpression of GAS6 promotes
cell proliferation and invasion in bladder cancer by activation of the
PI3K/AKT pathway. Onco Targets Ther. 2020; 13:4813-24.

25. Ekman C, Stenhoff J, Dahlback B. Gas6 is complexed to the sol-
uble tyrosine kinase receptor Axl in human blood. J Thromb
Haemost. 2010; 8:838.

Correspondence

Murat Akgül MD (Corresponding Author)
drmuratakgul@gmail.com - Assistant Professor
Tekirdag Namık Kemal University, Medical School, Urology Department, 
Süleymanpaşa, Tekirdağ, Turkey, 59030

Özgür Baykan, MD 
ozgurbaykan@gmail.com - Associated Professor 
Balıkesir University, Biochemistry Laboratory Balıkesir, Turkey, 10020

Zeynep Çağman, PhD
zeynep794@gmail.com - Assistant Professor 
Bezmialem University Pharmacy School, Biochemistry Department,  
Istanbul,Turkey, 34734

Mustafa Özyürek, PhD
mustafaozyurek1@gmail.com - Research Assistant 
Marmara University, Medical School, Physiology Department, Maltepe,  
Istanbul, Turkey, 34854

İlker Tinay, MD 
itinay@yahoo.com - Associated Professor 
Anadolu Medical Center, Gebze, Kocaeli, Turkey, 41400

Cem Akbal, MD
cakbal@gmail.com - Professor 
Acıbadem University, Urology Department, Altunizade-Üsküdar, Istanbul, 
Turkey, 34660

Fikriye Uras, PhD
furas@marmara.edu.tr - Professor 
Marmara University Pharmacy School, Biochemistry Department, Kadıköy- 
Istanbul,Turkey, 34734  

Levent Türkeri, MD
levent.turkeri@acibadem.com - Professor 
Acıbadem University, Urology Department, Altunizade-Üsküdar, Istanbul, 
Turkey, 34660