Stesura Seveso


Archivio Italiano di Urologia e Andrologia 2025; 97(2):13615

1

ORIGINAL PAPER

to the mucosa (Ta and carcinoma in situ “CIS”) or lamina
propria (T1), and tumors that invade the muscle (T2) and
beyond (T3, T4) which are defined as muscle- invasive
bladder cancer (MIBC). Approximately 75% of newly
diagnosed BCs are found at the non-muscle invasive
stage. NMIBCs are characterized by favorable survival
rates and with progression rates varying between 6-17%,
depending on the T stage of the tumor (Ta-CIS- T1) (4).
However, up to 67% of all patients with NMIBC may
experience disease recurrence. In contrast, in MIBC, five-
year survival rates drop to 60% for localized disease and
below 10% for metastatic disease (5). Efforts are being
made to identify new markers for BC to predict invasive
potential and prognosis of the disease. 
Transglutaminases are an enzyme family that perform
multiple calcium dependent posttranslational modifica-
tions of proteins. Tissue transglutaminase also known as
transglutaminase- 2 (TG2), is the most abundant member
of this family and it can be found in all cellular compart-
ments (nucleus, cytoplasm, organelles) as well as in the
extracellular space (6). In cellular environment, TG2 is
involved in various enzymatic activities such as transami-
dation, GTP/ATP hydrolyse, kinase, proteolytic and scaf-
folding. Through these activities, TG2 plays essential
roles in diverse physiological processes, including cell
growth and differentiation, adhesion, migration, angio-
genesis, autophagy, extracellular formation, apoptosis
(7). The oncogenic potential of TG2 has been demon-
strated in various cancer types such as breast carcinoma,
pancreatic adenocarcinoma, colorectal carcinoma and
central nervous system tumors in previous studies (8-11).
Resistance to systemic drugs and development of metastases
together account for nearly 90% of all cancer-related deaths.
Identifying of biomarkers that can promote tumor invasive-
ness, drug resistance and metastasis is an important goal, as
these proteins can be helpful in estimating the prognosis of
the disease and may serve as potential targets for the thera-
py. In carcinogenesis, TG2 has shown to play various roles.
Firstly, TG2 can promote epithelial- to mesenchymal transi-
tion (EMT), which is believed to be the first step of tumor
progression and metastasis (12). TG2 also contributes to
chemoresistance and promote the acquisition of cancer
stem-cell like properties of the tumor cells by activating NF-
κB and PI3K/Akt pathway (13). Additionally, TG2 influ-

Purpose: Transglutaminase-2 is associated
with tumor invasion, metastasis development,

chemoresistance and poor prognosis in various cancer types. 
In this study, our aim was to show the association between
increased transglutaminase-2 expression and the invasive pat-
tern of bladder cancer.
Materials and methods: Tumor tissues from eighty-eight patients
with bladder cancer (43 muscle-invasive, 45 non-muscle invasive
bladder cancer) were immunohistochemically evaluated for TG2
expression. 
Results: Transglutaminase-2 expression score was higher in
muscle- invasive bladder cancer compared to non-muscle inva-
sive bladder cancer tissues (5.37 ± 1.5 vs. 0.71 ± 1.4, p < 0.001).
No statistically significant difference was found in transglutami-
nase-2 expression scores between metastatic and non-metastatic
disease in MIBC group. Different tumor and lymph- node stages
in MIBC were also found to be not correlated with transglutami-
nase-2 expression scores. 
Conclusions: The over-expression of transglutaminase-2 is
 associated with invasive disease in bladder cancer. According to
our results, transglutaminase-2 has the potential to be useful for
predicting the invasion in bladder cancer and addressing
 treatment.

KEY WORDS: Transglutaminase-2; Muscle-invasive bladder
 cancer; Malignant neoplasm; Tumor biomarker.

Submitted 1 November 2024; Accepted 30 January 2025

INTRODUCTION
Bladder cancer (BC) is the 10th most common cancer
worldwide, and its incidence is rising, especially in devel-
oped countries. Bladder cancer is more common in men
than women, with lifetime risk of 1 to 27 in men and 1 to
89 for women, respectively (1). The advanced age is now
recognized as the greatest risk factor for bladder cancer,
with the average age of BC diagnosis being 70 years (2).
Tobacco consumption is the most important modifiable
risk factor for bladder cancer, accounting nearly 50% of
all cases. Urothelial carcinoma is the most common sub-
type of BC (3).
Bladder cancer is divided into two main categories: non-
muscle invasive bladder cancer (NMIBC), which is confined

Increased expression of transglutaminase-2 
is associated with invasive disease in bladder cancer

Yavuz Karaca 1, Şükran Kayıpmaz 2, Dilek Telci 3, Oktay Akça 4

1 Department of Urology, Sancaktepe Şehit Prof. Dr. İlhan Varank Research and Training Hospital, Istanbul, Türkiye;
2 Department of Pathology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul, Türkiye;
3 Faculty of Engineering, Department of Genetics and Bioengineering, Yeditepe University, Istanbul, Türkiye;
4 Department of Urology, Bahçeşehir University, Istanbul, Türkiye.

DOI: 10.4081/aiua.2025.13615

Summary



Archivio Italiano di Urologia e Andrologia 2025; 97(2):13615

Y. Karaca, Ş.Kayıpmaz, D. Telci, O. Akça

2

ences the tumor micro-environment by cross-linking extra-
cellular matrix proteins, thereby facilitating tumor- ECM
interaction. Through these mechanisms, TG2 has shown to
be associated with increased cancer cell adhesion, migra-
tion, metastasis and invasion in different cancer types (14).
In this study, our aim was to evaluate the role of transg-
lutaminase-2 in bladder cancer. 

MATERIALS AND METHODS
After the approval of local ethics committee (No:
2021/514/202/5), cases dated between January 2014 and
May 2021 involving transurethral resections and radical
cystectomies for bladder cancer in our Urology department
database were retrospectively scanned. All demographic
characteristics, clinical and pathological parameters were
evaluated. A total of 46 patients with MIBC were identified
for the study group and 45 patients with NMIBC were

selected as the control group. The control group were con-
sisted of patients with demographic characteristics similar
to the study group. Exclusion criteria were: history of neo-
adjuvant therapy for BC, history of intravesical therapy and
non-urothelial carcinomas of bladder (Figure 1). A total of
91 patients were included into this study. 
Paraffin-embedded cancer tissues of these patients were
extracted from Pathology Department’s archives. 

Immunohistochemical evaluation
Formalin fixed paraffin-embedded tissues were used for
immunohistochemical evaluation. After the inspection of
all hematoxylin-eosine-stained slides of the tumor samples,
a single paraffin-embedded block with the most evident
tumor tissue was selected for each case. Tissue sections
obtained from the paraffin blocks were fumigated for one

day. The next day, the slides were placed in a Benchmark
XT/IHC system staining module (Roche Diagnostics, Basel,
Switzerland). Deparaffinization, antigen retrieval with
EDTA, antibody incubation (Transglutaminase-2 CUB 7402,
Invitrogen, Massachusetts, USA, MA-12739, 1/200 dilution, 32
minutes incubation), amplification and counter staining with
HE processes were performed respectively. After these
steps, slides were washed, dried and sealed. 

Microscopic assessment
According to the manufacturer’s manuals, tumor samples
from an invasive ductal breast adenocarcinoma case were
selected as control tissue. Efficacy and the reaction con-
ditions of the antibody were determined by using this
control tissue. 
The assessments of the tumor tissues were performed by
SK, who is an experienced uro-pathologist with the par-
ticipation of one of the urologists (YK) as an observer.

Both evaluators were blinded to the
clinical and pathological features of
the patients. 
All tumor slides were evaluated
with microscope under 4x, 10x,
20x, 40x and 100x magnifications
when necessary. Based on previous
studies (15), cytoplasmic and
membranous staining of the cells
was assessed and according to
 findings in 4x, a semi-quantitative
chart was designed. Staining per-
centage was scored between 0-4
points (< 10%-0 points, 10-30%
1 point, 30-50%-2 points, 50-
70%-3 points and > 70%-4 points)
and staining intensity was scored
between 0-3 points (no staining- 0
points, weak-1 point, moderate-2
points and strong- 3 points) with
maximum total score of 7 points
(Table 1).
Three patients with “nested variant
of urothelial carcinoma” from MIBC
group were excluded from the
study due to a lack of staining with

Table 1. 
The semi-quantitative chart for transglutaminase-2 antibody
staining scoring system.

Staining parameter Points
Staining percentage (% score)

< 10% 0
10-30% 1
30-50% 2
50-70% 3
> 70% 4

Staining intensity (intensity score)

No staining 0
Weak 1
Moderate 2
Strong 3

Figure 1. 
PRISMA diagram showing the selection of the patients.



Archivio Italiano di Urologia e Andrologia 2025; 97(2):13615

3

Increased expression of transglutaminase-2 is associated with invasive disease in bladder cancer

the antibody. A total of 88 patients with BC were includ-
ed into this study. 
The microscopic images of immunohistochemical TG2
antibody staining of the tissues are presented in Figure 2
and Figure 3.

Statistical analysis
Statistical analysis was performed with IBM SPSS software
(ver. 26 for MacOS, IBM, USA). Distribution of the vari-
ables was measured by Kolmogorov-Smirnov test. All
demographic, clinical and histopathological parameters
were analyzed using Kruskal-Wallis test, Mann-Whitney
U test and Chi-square test. A p value < 0.05 was consid-
ered as statistically significant. 

RESULTS
A total of 88 patients were included in this study. Group
1 consisted of 43 MIBC patients (40 men, 3 women), and
Group 2 consisted of 45 NMIBC patients (41 men, 4
women). Three patients with nested variant of MIBC were
excluded (Figure 1). The average age was 63.4 ± 10.3
years in Group 1 and 61.1 ± 11.9 years in Group 2 (p =
0.447). All 88 patients were diagnosed with urothelial
carcinoma of the bladder. All patients in Group 1 had
high-grade carcinoma, while 3 patients (6.6%) in Group
2 had high-grade carcinoma (Table 2).
The average transglutaminase-2 (TG2) staining score was
significantly higher in Group 1 compared to Group 2
(5.37 ± 1.5 vs. 0.71 ± 1.4, p < 0.001) (Table 3).
Further analysis of patients with MIBC (Group 1) was

Figure 2. 
Microscopic images of immunohistochemical TG2 staining 
of the tissues. 
A. 57 years old man, MIBC, pT3b, % score: 4/intensity score: 
3 total score: 7. 
B. 68 years old woman, MIBC with sarcomatoid differentiation,
pT4, % score: 4/intensity score: 3 total score: 7. 
C. 44 years old man, low grade NMIBC, pTa, % score: 0/intensity
score: 0 total score: 0. 
D. 51 years old man, low grade NMIBC, pTa, % score: 0/intensity
score: 0 total score: 0.

Figure 3. 
Microscopic images of immunohistochemical TG2 staining 
of the tissues. 
A. 63 years old man, MIBC with nested variant, T2, % score:
0/intensity score: 0 total score: 0. 
B. 54 years old man, MIBC, T3a, % score: 2/intensity score: 
1 total score 3.

Table 3. 
The comparison of mean transglutaminase-2 staining scores
of two groups.

Group 1 Group 2 P value
(MIBC group) (NMIBC group)

TG2 staining score (mean ± SD) 5.37 ± 1.5 0.71 ± 1.4 < 0.001 

Table 2. 
Demographic, clinical and pathological parameters 
of two groups.

Group no Group 1 (MIBC group) Group 2 (NMIBC group)
Patient number 43 45

Age 63.40 ± 10.3 61.13 + 11.9

Sex (n, %)
Men 40 (93%) 41 (91.1%)
Women 3 (7%) 4 (8.9%)

Tumor histology (n, %) Urothelial carcinoma – 43 (100%) Urothelial carcinoma – 45 (100%)

Tumor stage (n, %)
pT2 16 (37%)
pT3 15 (34.8%) Ta – 45 (100%)
pT4 12 (27.9%)

Lymph node involvement (n, %)
N0 18 (41.8%) N0 - 45 (100%)
N1 12 (27.9%)
N2 11 (25.5%)
N3 2 (4.6%)

Tumor grade (n, %) High grade – 43 (100%) Low grade - 42 (93.3%)
High grade - 3 (6.6%)

A. B.

A. B.

C. D.



Archivio Italiano di Urologia e Andrologia 2025; 97(2):13615

Y. Karaca, Ş.Kayıpmaz, D. Telci, O. Akça

4

conducted to identify factors potentially influencing TG2
expression. No statistically significant difference in TG2
staining scores was observed between metastatic and
non-metastatic MIBC patients (5.39 ± 1.6 vs. 5.33 ± 1.4,
p = 0.824) (Table 4). Additionally, there was also no sta-
tistically significant difference in TG2 staining scores
between tumors at different tumor stages (p = 0.142) or
lymph node stages (p = 0.905) (Table 5).
Interestingly, three patients with the nested variant of
MIBC showed no staining with the transglutaminase-2
antibody.

DISCUSSION
Our study reveals a significant upregulation of transgluta-
minase-2 (TG2) in MIBC compared to NMIBC (5.37 ± 1.5
vs 0.71 ± 1.4, p < 0.001). While TG2 expression was sig-
nificantly elevated in invasive tumors compared to non-
invasive tumors, it showed no correlation with lymph
node involvement, tumor stage, or metastatic status in
within the MIBC subgroup, highlighting its presence
across all stages of MIBC without significant variations.
Interestingly, the absence of TG2 staining in the nested
variant MIBC cases highlights potential histological vari-
ability, suggesting that TG2 expression is not uniform
across all bladder cancer variants. 
One of the key ways TG2’s contributions to cancer pro-
gression is by promoting epithelial-to-mesenchymal transi-
tion (EMT) of cancer cells. EMT is a major pathway of the
tumor cells during cancer progression (16). TG2 activates
cancer cells EMT through FAK, Akt and NF-kB pathway
(17). During EMT, epithelial cells lose their cell-to-cell
adhesion and take on a more mobile, mesenchymal-like
state. This leads to the loss of epithelial markers like 

E-cadherin and an increase in mesenchymal markers
such as vimentin and fibronectin. These changes enable
cancer cells to become more migratory and invasive, sig-
nificantly increasing their potential of invasion and form-
ing distant metastases. Secondly, TG2 overexpression has
been linked to the acquisition of stem-cell like properties
of the cancer cells which is associated with increased
tumor-initiating capacity and chemoresistance (18).
Additionally, in carcinogenesis TG2 modulates the tumor
microenvironment by crosslinking ECM proteins and
enhances cell adhesion, migration and tumor survival. 
When compared to other studies, our findings are coher-
ent with prior observations that link TG2 expression to
tumor aggressiveness in various malignancies. In bladder
cancer, Hager et al. observed that TG2 is primarily
expressed in grade 3 and 4 muscle- invasive tumors,
while it remains undetectable in normal urothelium and
low-grade papillary tumors. Their study further demon-
strated a lack of TG2 staining in distant solid organ
metastases, suggesting TG2’s role may be limited to the
local invasive phase rather than systemic metastatic dis-
ease. In breast cancer, Kumar et al. showed increased
expression of TG2 induces EMT and stem-cell properties
in mammary epithelial cells therefore promoting aggres-
sive disease and metastasis (19). In a study by Shinde et
al. it was shown that TG2 contribute to resistance to
chemotherapy in HER2 positive breast cancer cells
through the activation of the NF-κB signaling pathway
(20). In a review, Li et al. showed that increased TG2
expression is elevated in lung and bone metastasis and
TG2 can mediate multiple therapy resistance to
chemotherapeutic drugs and immune check-point
inhibitors by modulating tumor microenvironment and
promoting EMT and CSC-like properties (21).
In colorectal cancer, increased expression of TG2 has
shown to be associated with lower disease-free survival
(DFS), overall-survival (OS) and earlier relapse (22). In an
invitro study, overexpression of TG2 in colorectal cancer
stem-cells has shown to be associated with increased
metastatic potential via EMT pathway and TG2 knock-
down reversed the EMT proving the potential of TG2 as
a therapeutic target for aggressive CRC (23).
In ovarian cancer cells, TG2 binds directly to fibronectin
and stabilizes extracellular matrix by enhancing
fibronectin- integrin B-1 complex. By activating integrin-
linked kinase (ILK), TG2 favors cancer-cell adhesion, extra-
cellular matrix reorganization, migration and metastatic
spread. Statistical analyses showed high expression of TG2
and ILK is associated with lower overall-survival in ovari-
an cancer. In-vitro knockdown of TG2 demonstrated sig-
nificant reduction of cancer cell adhesion and metastatic
potential and hence showing the potential role of TG2 as
a therapeutic target for ovarian cancer (24). 
In non-small-cell lung cancer (NSCLC), higher TG2 express-
ing tumors have found to be associated with more
advanced stage/metastatic disease, increased chemotherapy
resistance, lower DFS, poorer OS compared to lower TG2
expressed tumors (25). It has also reported that inhibition
of TG2 in lung cancer increase radiosensitivity of tumor
cells (26). Corelated with these results, TG2 may serve as a
prognostic factor in lung cancer. In pancreatic cancer,
tumor with higher TG2 expressions were found to have

Table 4. 
The comparison of mean transglutaminse-2 scores 
in metastatic and non-metastatic MIBC patients.

Present  Not present P value
(Mean TG2 score (Mean TG2 score
+ SD, number) + SD, number)

Metastasis 5.39 ± 1.6 (n: 28) 5.33 ± 1.4 (n: 15) 0.824 *

* Mann Whitney- U test.

Table 5. 
The comparison of mean transglutaminse-2 scores 
in MIBC patients subgroup regarding to T and N stages.

Mean TG2 score (number) P value
T stage

2 5.31 ± 1.44 (n: 16) 0.142 **

3 5.93 ± 1.38 (n: 15)
4 4.75 ± 1.71 (n: 12)

N stage 
0 5.33 ± 1.41 (n: 18) 0.905 **

1 5.25 ± 1.71 (n: 12)
2 5.73 ± 1.34 (n: 11)
3 4.5 ± 3.53 (n: 2)

** Kruskal- Wallis test.



Archivio Italiano di Urologia e Andrologia 2025; 97(2):13615

5

Increased expression of transglutaminase-2 is associated with invasive disease in bladder cancer

poorer clinicopathologic features (higher nodal metastasis,
advanced clinical stage, less chemotherapy sensitivity,
increased tumor invasion and metastatic potential) (11).
In this study we were able to detect higher expression of
TG2 in muscle invasive bladder cancer compared to non-
muscle invasive bladder cancer. Our results were corelat-
ed with previous findings about the potential roles of
transglutaminase-2’s in advanced malignancy in various
cancer types. But our study is not without some limita-
tions. Firstly, the small number of samples is the main
limitation of this study. Secondly, clinical data of the
patients are not obtained thus no commentary can be
made on the effects of transglutaminase-2 on overall-sur-
vival and disease-free survival rates in bladder cancer.
Nevertheless, considering that muscle-invasive BC has
lower overall- survival and disease-free survival com-
pared to NMIBC, higher TG2 can be held responsible for
worse prognosis in bladder cancer. However, further clin-
ical data are necessary for this purpose. On the other
hand, our study is one of the very few studies on this sub-
ject and our results showed clearly that TG2 expression is
stronger in invasive bladder cancer tissues compared to
non-invasive tumors. Our findings may form a basis for
further clinical studies. 

CONCLUSIONS
In this study, our data showed that higher expression of
transglutaminase-2 is associated with increased invasion
potential in bladder cancer. According to our results,
transglutaminase-2 has the potential for predicting prog-
nosis of bladder cancer and being a therapeutic target.

REFERENCES
1. Richters A, Aben KKH, Kiemeney LALM. The global burden of uri-
nary bladder cancer: an update. World J Urol. 2020; 38:1895-1904. 

2. Shariat SF, Sfakianos JP, Droller MJ, et al. The effect of age and
gender on bladder cancer: a critical review of the literature. BJU Int.
2010; 105:300-308.

3. Burger M, Catto JW, Dalbagni G, et al. Epidemiology and risk fac-
tors of urothelial bladder cancer. Eur Urol. 2013; 63:234-41. 

4. Siregar GP, Parwati I, Noegroho BS, et al. The association between
serum hypoxia inducible factor-1α level and urothelial bladder can-
cer: A preliminary study. Arch Ital Urol Androl. 2023; 95:11292. 

5. Lenis AT, Lec PM, Chamie K, Mshs MD. Bladder Cancer: A
Review. JAMA. 2020; 324:1980-1991.

6. Odii BO, Coussons P. Biological functionalities of transglutaminase 2
and the possibility of its compensation by other members of the transg-
lutaminase family. ScientificWorldJournal. 2014; 2014:714561.

7. Tabolacci C, De Martino A, Mischiati C, et al. The Role of Tissue
Transglutaminase in Cancer Cell Initiation, Survival and
Progression. Med Sci (Basel). 2019; 7:19.

8. Malkomes P, Lunger I, Oppermann E, et al. Transglutaminase 2
is associated with adverse colorectal cancer survival and represents a
therapeutic target. Cancer Gene Ther. 2023; 30:1346-1354.

9. Chang W, Gao W, Liu D, et al. The upregulation of TGM2 is asso-
ciated with poor prognosis and the shaping of the inflammatory
tumor microenvironment in lung squamous cell carcinoma. Am J
Cancer Res. 2024; 14:2823-2838. 

10. Buccarelli M, Castellani G, Fiorentino V, et al. Biological
Implications and Functional Significance of Transglutaminase Type
2 in Nervous System Tumors. Cells. 2024; 13:667. 

11. Verma A, Wang H, Manavathi B, et al. Increased expression of
tissue transglutaminase in pancreatic ductal adenocarcinoma and its
implications in drug resistance and metastasis. Cancer Res. 2006;
66:10525-10533. 

12. Shao M, Cao L, Shen C, et al. Epithelial-to-mesenchymal transi-
tion and ovarian tumor progression induced by tis- sue transglutam-
inase. Cancer Res. 2009; 69:9192-9201. 

13. Cao L, Shao M, Schilder J, et al. Tissuetransglutaminase links
TGF-beta, epithelial to mesenchymal transition and a stem cell phe-
notype in ovarian cancer. Oncogene 2012; 31:2521-2534.

14. Eckert RL, Kaartinen MT, Nurminskaya M, et al. Transglutaminase
regulation of cell function. Physiol Rev. 2014; 94:383-417.

15. Erdem S, Yegen G, Telci D, et al. The increased transglutaminase
2 expression levels during initial tumorigenesis predict increased risk
of metastasis and decreased disease-free and cancer-specific survivals
in renal cell carcinoma. World J Urol. 2015; 33:1553-1560.

16. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mes-
enchymal transitions in development and disease. Cell. 2009;
139:871-890.

17. Chen X, Adhikary G, Newland JJ. et al. Transglutaminase 2
Binds to the CD44v6 Cytoplasmic Domain to Stimulate
CD44v6/ERK1/2 Signaling and Maintain an Aggressive Cancer
Phenotype. Mol. Cancer Res. 2023; 21:922-932. 

18. Mani SA, Guo W, Liao MJ, et al. The epithelial-mesenchymal
transition generates cells with properties of stem cells. Cell. 2008;
133:704-715.

19. Kumar A, Gao H, Xu J, et al. Evidence that aberrant expression
of tissue transglutaminase promotes stem cell characteristics in mam-
mary epithelial cells. PLoS One. 2011; 6:e20701.

20. Shinde A, Kulkoyluoglu Cotul E, Chen H, et al. Transglutaminase-
2 mediates acquisition of neratinib resistance in metastatic breast can-
cer. Mol Biomed. 2022; 3:19. 

21. Li M, Wang X, Hong J, et al. Transglutaminase 2 in breast can-
cer metastasis and drug resistance. Front Cell Dev Biol. 2024;
12:1485258. 

DECLARATIONS

Ethical approval and consent for participate: This study was
approved by the local ethical committee (No: 2021/514/202/5).
All patients consented for participation. 

Consent for publication: All patients consented for publica-
tion. 

Availability of data and material: All data and material of
this study is available for further assessment from the corre-
sponding author. 

Competing interests: None. 

Funding: This study was funded by Audobon Bioscience Türkiye. 

Authors' contributions: Design of the study: OA, DT;
Acquisition of data: YK, SK; Analysis of the data: YK, OA;
Revision of the article: All authors Approval of the article: All
authors. 

Acknowledgments: None. 



Archivio Italiano di Urologia e Andrologia 2025; 97(2):13615

Y. Karaca, Ş.Kayıpmaz, D. Telci, O. Akça

6

22. Fernández-Aceñero MJ, Torres S, Garcia-Palmero I, et al.
Prognostic role of tissue transglutaminase 2 in colon carcinoma.
Virchows Arch. 2016; 469:611-619.

23. Kang S, Oh SC, Min BW, Lee DH. Transglutaminase 2 Regulates
Self-renewal and Stem Cell Marker of Human Colorectal Cancer
Stem Cells. Anticancer Res. 2018; 38:787-794.

24. Condello S, Prasad M, Atwani R, Matei D. Tissue transglutami-

nase activates integrin-linked kinase and β-catenin in ovarian can-
cer. J Biol Chem. 2022; 298:102242.

25. Chihong Z, Yutian L, Danying W, et al. Prognostic value of
Transglutaminase 2 in non-small cell lung cancer patients.
Oncotarget. 2017; 8:45577-45584.

26. Huaying S, Dong Y, Chihong Z, et al. Transglutaminase 2
Inhibitor KCC009 Induces p53-Independent Radiosensitization in
Lung Adenocarcinoma Cells. Med Sci Monit. 2016; 22:5041-5048.

Correspondence
Yavuz Karaca (Corresponding author)
mdyavuzkaraca@gmail.com
Feyzullah mh. Oğuzhanlı cad. Akay apt. no: 24-26 Kat: 5 Daire: 12
Maltepe/İstanbul
Postal zip code: 34843

Şükran Kayıpmaz
sukransarikaya@yahoo.com
Department of Pathology, Kartal Dr. Lütfi Kırdar City Hospital, Istanbul,
Türkiye

Dilek Telci
telcidilek@gmail.com
Faculty of Engineering, Department of Genetics and Bioengineering,
Yeditepe University, Istanbul, Türkiye 

Oktay Akça
akcaoktay@yahoo.com
Department of Urology, Bahçeşehir University, Istanbul, Türkiye