Clin Exp Pharmacol Physiol. 2017;44:1099–1105. wileyonlinelibrary.com/journal/cep
|
1099 © 2017 John Wiley & Sons Australia, Ltd
Received: 23 May 2017
|
Revised: 10 July 2017
|
Accepted: 25 July 2017
DOI: 10.1111/1440-1681.12840
ORIGINAL ARTICLE
Differential expression of two genes Oct-4 and MUC5AC
associates with poor outcome in patients with gastric cancer
Milad Javanbakht
1
| Jamal Akhavanmoghadam
2
| Amir Jouya Talaei
3
|
Maryam Aghyani
4
| Mohamad Mozafari
4,5
| Leila Khedmat
6
| Mahdi Mohebbi
4
1
School of Medicine Science, Islamic Azad
University, Sarab, Iran
2
Trauma Research Center, Baqiyatallah
University of Medical Sciences, Tehran, IR, Iran
3
Department of Genetics, Faculty of Life
Science, Azad University of Tehran Medical
Sciences Branch, Tehran, Iran
4
General practitioner (GP), Doctor of Medicine
(MD), Tehran and Tabriz, Iran
5
Graduated from Tabriz University of Medical
Science, Tabriz, Iran
6
Department of Social Medicine, Tehran
University of Medical Sciences, Tehran, Iran
Correspondence
Mohamad Mozafari, Graduated from Tabriz
University of Medical, Science, Tabriz, Iran.
Email: mohamad2mzf@gmail.com
Leila Khedmat, Department of Social
Medicine, Tehran University of Medical
Sciences, Tehran, Iran.
Email: leilakhedmat@yahoo.com
Summary
Gastric cancer (GC) is the most frequent leading cause of cancer-associated mortality
worldwide that is linked to poor prognosis due to the lack of appropriate biomarkers.
Our aim was to evaluate the MUC5AC and Oct-4 expression levels in GC and to assess
their association with clinical factors. Immunohistochemical analysis (IHC) and qRT-
PCR were performed in GC patients to examine the MUC5AC and Oct-4 expression
levels. The mRNA level of MUC5AC was significantly decreased in tumour tissues
compared with non-cancerous tissues (1.11 ± 0.69 vs 3.7 ± 0.71; P = .024). On the
other hand, Oct-4 mRNA level was upregulated in tumour tissues as compared to
normal tissues (2. 86 ± 0.78 vs 0.87 ± 0.54; P = .0015). Decreased expression of
MUC5AC was detected in 27 patients (67.5%), while high to moderate expression
levels were observed in 13 cases (32.5%), but in normal tissues the expression levels
of MUC5AC were increased (P = .001). The decreased expression of MUC5AC was
associated with aggressive tumour characteristics, such as TNM stage (P = .023), his-
tologic type (P = .012) and lymph node metastasis (P = .001). High expression of Oct-4
was detected in 24 tumour tissues (60%), while 16 cases (40%) showed low expression
level. Increased Oct-4 expression was correlated with clinicopathological characteris-
tics such TNM stage (P = .002), histologic type (P = .008) and lymph node metastasis
(P = .001). Our results showed that high Oct-4 expression and the reduction of
MUC5AC expression may be involved in the progression and an unfavorable progno-
sis of GC.
KEYWORDS
gastric cancer, IHC, MUC5AC, Oct-4, QRT-PCR
1 | INTRODUCTION
Despite development of therapeutic strategies, the clinical outcome of
gastric cancer (GC) remains poor. However, effective prognostic/pre-
dictive markers for multimodal therapy are currently required. Mucins
are a group of extremely glycosylated extracellular ingredients of the
mucousal layer. Mucins have been described to be linked to protection,
lubrication and hydration of the external surface of human epithelial
tissue layers. It has been reported that expression and glycosylation of
mucins are associated with carcinogenesis including invasion, prolifer-
ation and regulation of tumour cells.
1-3
MUC5AC mucin has protective
role in the surface of the stomach from chemical, microbial and, me-
chanical damage.
4
MUC5AC was reported to be implicated in gastric
carcinogenesis with Lowe level of expression. Moreover, it has been
indicated that MUC5AC expression level can be linked to severity of
GC.
5-7
Downregulation of MUC5AC expression has been determined
in certain neoplastic lesions and might be appeared in advanced
GC.
8-11
Oct-4 has been revealed that it associated with the