Insulin-like growth factor 1 serum levels in different stages of gastric cancer and their association with Helicobacter pylori status
Graphical Abstract
Introduction
Gastric cancer (GC) is considered the fifth most common malignancy and the fourth most lethal cause of cancer worldwide [1], [2]. Nearly a million new cases of GC are identified, and over 700,000 people die of this disease yearly [3]. Most GC patients are diagnosed at the end stage, resulting in a poor prognosis and a narrow range of therapeutic alternatives [4]. Some studies on gastric cells have revealed the importance of growth factors, like insulin-like growth factor 1 (IGF-1), in tumorigenesis and cancer development [5]. The high circulating IGF-1 may increase the risk of colorectal, pancreatic, gastric, prostate, and esophageal cancers. It can facilitate metastasis due to cell migration and invasion [6]. The interaction between IGF-1 and IGF-1R can activate two main signaling pathways: phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) and RAS/RAF/the extracellular signal-regulated kinase (ERK). These pathways regulate cellular processes, including cell proliferation, differentiation, and apoptosis [7], [8].
Additionally, the elevated level of IGF-1 was related to less tumor differentiation, a high stage, metastasis, and positive Helicobacter pylori (H. pylori) status [9], [10], [11]. In this setting, H. pylori infection is the most critical risk factor that dysregulates two main signaling pathways; PI3K/AKT/mTOR and RAS/RAF/ERK, which are involved in gastric cancer development [12], [13]. It is one of the primary etiological factors associated with antral gastritis and has been categorized as a Class 1 carcinogen by the World Health Organization [14], [15]. The studies showed that interaction between H. pylori and IGF-1 might enhance GC development, so its eradication can decrease serum IGF-1 levels [16], [17]. In persistent infections, H. pylori can further increase the risk of inflammation and, finally, non-cardia gastric adenocarcinoma [18]. The constant inflammation by H. pylori can induce the release of pro-inflammatory cytokines, which can modify the secretion and the biological functions of IGF-1 [19]. Therefore, the present study aimed to assess IGF-1 serum levels and the expression of candidate genes in the different stages of GC patients and their association with H. pylori status.
Section snippets
Study population
A total of 90 tissue samples, including 60 tumors from gastric cancer (GC) patients and 30 non-tumor gastric mucosae from noncancerous (NC) individuals, were used in the present study. All participants were admitted to Rasool Akram Hospital, Tehran, Iran, from October 2016 to October 2018. The samples were extracted using endoscopy procedures. They were diagnosed based on histopathological examinations according to the tumor–node–metastasis (TNM) staging system [20]. The NC individuals with
Clinicopathological data
The demographic and clinicopathological information are shown in Table 2. The mean age of the GC and the NC participants was 56.2 ± 11.5 and 54.4 ± 12.6 years, of which 44 (73.2%) and 17 (56.6%) were men, and 16 (26.8%) and 13 (43.4%) were women, respectively. Moreover, 41 (69.6%) and 13 (43.3%) participants of the GC and NC groups were positive for H. pylori status, respectively. Other clinical factors, including tissue location, cell differentiation, TNM staging, tumor invasion depth, lymph
Discussion
Our findings showed IGF-1 serum levels and the candidate proteins were meaningfully increased in the advanced GC stages compared to the early ones. Likewise, their levels were significantly higher in GC patients with positive H. pylori than the negative H. pylori status. So, IGF-1 and H. pylori infection may be therapeutic targets in GC patients.
Many studies have shown that the abnormal expression of IGF-1 could be used as a valuable biological marker for early diagnosis and treatment
Conclusion
As a result, high IGF-1 serum levels and positive H. pylori status were associated with advanced GC patients. Although signaling mechanisms of GC progression caused by high IGF-1 levels and H. pylori infection have not been fully revealed, IGF-1 inhibition and H. pylori eradication might be new therapeutic targets. However, further studies are needed to find the best strategy for GC treatments.
Acknowledgment
This study was co-funded by the Tehran University of Medical Sciences (Grant Number: 29025) and the Iran University of Medical Sciences (Grant Number: 26256).
Author contributions
FG: manuscript preparation, sample collection, processing, and data analysis. AMA: study conception and design and article revision. SA: clinical annotation and sample collection. SI: article revision. MM: sample collection, diagnostic of histological and sample processing.
Conflict of interest
The manuscript authors have no conflicts of interest to declare and
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Ali Mohammad Alizadeh and Shahram Agah contributed equally to this work.