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Journal of Molecular Histology (2018) 49:389–398
https://doi.org/10.1007/s10735-018-9779-y
ORIGINAL PAPER
Over-expression of IQGAP1 indicates poor prognosis in head and neck
squamous cell carcinoma
Cong‑Cong Wu
1
· Hao Li
1
· Yao Xiao
1
· Lei‑Lei Yang
1
· Lei Chen
1
· Wei‑Wei Deng
1
· Lei Wu
1
· Wen‑Feng Zhang
1,2
·
Zhi‑Jun Sun
1,2
Received: 20 March 2018 / Accepted: 28 May 2018 / Published online: 30 May 2018
© Springer Science+Business Media B.V., part of Springer Nature 2018
Abstract
IQ-domain GTPase-activating protein 1 (IQGAP1) is associated with the development and progression of many human can-
cers. We aimed to investigate the expression and clinicopathological significances of IQGAP1 in head and neck squamous cell
carcinoma (HNSCC). In this study, immunohistochemical staining of IQGAP1, co-inhibitory immune checkpoint molecules
and macrophage markers were performed in human HNSCC samples to analyze the expression and correlation with clinico-
pathological characteristics. Immunoreactivity of IQGAP1 was also detected in immunocompetent mouse HNSCC tissue.
We found that IQGAP1 expression level was significantly increased in human HNSCC compared with dysplasia and normal
mucosa, and the expression of IQGAP1 in HNSCC was positively associated with advanced lymph node status. Besides,
our data indicated that patients with higher IQGAP1 expression exhibited poor overall survival compared with patients with
lower IQGAP1 expression. Furthermore, this study demonstrated that IQGAP1 expression was positively associated with
TIM3, Galectin-9 (TIM3 ligand), B7H4, macrophage markers CD68 and CD163. In conclusion, these findings suggest that
over-expression of IQGAP1 in human HNSCC may indicate poor prognosis.
Keywords IQ-domain GTPase-activating protein 1 · Head and neck squamous cell carcinoma · Prognosis · Transgenic
mice · Tissue microarray
Introduction
Head and neck squamous cell carcinoma (HNSCC) is
the seventh most common cancer worldwide (Saleh et al.
2018), and accounts for 90% of the tumors that arise in the
head and neck region (Ali et al. 2017). A number of certain
environment and lifestyle risk factors have been identified
thus far for HNSCC, including tobacco smoking, alcohol
consumption, human papilloma virus (HPV) infection and
suppressive immune status (Ali et al. 2017; Leemans et al.
2018). HNSCC represents a devastating type of malignancy
with high morbidity and mortality leading to patient disfig-
urement and death (Moy et al. 2017). Present-day treatment,
surgery, radiotherapy or chemotherapy or a combination of
these three, has had not improved overall survival (OS) over
the past few decades (Moy et al. 2017; Schoop et al. 2009).
Therefore, novel molecular targets in HNSCC should be
exploited to provide more efficient therapies.
IQ-domain GTPase-activating protein 1 (IQGAP1) is a
scaffold protein (Johnson et al. 2009) that binds to distinct
proteins, such as F-actin (Mataraza et al. 2007), calmodulin
(Andrews et al. 2012) and E-cadherin (Fram et al. 2014).
Through interacting with its target proteins, IQGAP1 can
integrate components of a single signaling pathway [e.g.,
MAPK (Zhou et al. 2014) or PI3K (Osman 2015)]. Expres-
sion analysis has indicated that IQGAP1 was over-expressed
in multiple tumor types, including gastric cancer (Sugimoto
Zhi-Jun Sun is willing to handle correspondence at all stages of
refereeing and publication, also post-publication.
Electronic supplementary material The online version of this
article (https ://doi.org/10.1007/s1073 5-018-9779-y) contains
supplementary material, which is available to authorized users.
* Zhi-Jun Sun
sunzj@whu.edu.cn
1
The State Key Laboratory Breeding Base of Basic Science
of Stomatology (Hubei-MOST) & Key Laboratory of Oral
Biomedicine Ministry of Education, School & Hospital
of Stomatology, Wuhan University, Wuhan, China
2
Department of Oral Maxillofacial-Head Neck Oncology,
School and Hospital of Stomatology, Wuhan University, 237
Luoyu Road, Wuhan 430079, Hubei Province, China
@Phil_Robichaud
@deepthiw
@JoseServera