Association of PYGO2 and EGFR in esophageal squamous cell carcinoma

Abstract

Wnt signaling is an important evolutionary conserved pathway that is not only involved in determination of cellular development, self-renewal, and fate, but also has significant roles in tumor development and progression. Deregulation of the Wnt/β-catenin signaling pathway and aberrant expression of its components is commonly observed in solid tumors. Such aberrant regulation of Wnt signaling is commonly related to either malfunction of its components or crosstalk with other cellular processes such as the epidermal growth factor receptor (EGFR) signaling cascade. Therefore, identification of the roles of major involved components may be useful to identify new therapeutic targets for cancer treatment. In this study, we assessed EGFR and PYGO2 mRNA expression in tumors and margin normal tissues from 55 esophageal squamous cell carcinoma (ESCC) patients using real-time qRT-PCR, and evaluated clinicopathology relative to the two genes' expression levels. Significant PYGO2 and EGFR overexpression was observed in 30.9 % (P = 0.017) and 38.2 % (P = 0.006) of tumors, respectively. PYGO2 and EGFR expression were significantly associated not only with each other (P < 0.001), but also with tumor staging and depth (P < 0.001). Furthermore, PYGO2 expression was significantly correlated with the tumor grade (P = 0.043) and size (P = 0.023). We identify PYGO2 as a new molecular marker of invasive tumors, introducing its probable oncogenic role in ESCC progression and aggressiveness. In line with other reports, we also illustrate the oncogenic function of EGFR in the development of ESCC through advance stages. We also observed a significant correlation between PYGO2 and EGFR in ESCC tumors, which reveals a mutual convergent influence of these factors in tumor progression and development. Considering aberrant expression, mutual positive feedback, and the significant clinical relevance of these genes in ESCC, we introduce them as appropriate therapeutic targets in adjuvant therapy of ESCC.

WNT and NOTCH signaling pathways as activators for epidermal growth factor receptor in esophageal squamous cell carcinoma

“…The present study was in line with our previous projects about EGFR and MSI1 in ESCC patients to find a probable correlation between these markers and introduce a panel of diagnostic markers [14, 25, 26, 28–30]. We have recently reported a direct correlation between PYGO2, the main transcription factor of the WNT pathway, and EGFR, one of the target genes in the WNT pathway [25].…”

“…Regarding our recent publications, we have reported the role of EGFR and MSI1 in separate studies [25, 26]. Here, a probable mutual correlation between such markers was assessed for the first time among ESCC patients.…”

“…We have recently reported a direct correlation between PYGO2, the main transcription factor of the WNT pathway, and EGFR, one of the target genes in the WNT pathway [25]. On the other hand, EGFR also regulates beta-catenin stability in cells, providing positive feedback for PYGO2 [31].…”

“…Subsequently, cDNA synthesis performed using the First-Strand Synthesis kit (Fermentas, Lithuania). Finally, the levels of EGFR and MSI1 mRNA expression in normal and fresh tissues were assessed using comparative relative real-time PCR (SYBR Green, AMPLIQON, Denmark; Stratagene Mx-3000P, USA) in duplicate reactions with specific primer sequences [25, 26]). Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as a normalizer [27].…”

Role of Msi1 and MAML1 in Regulation of Notch Signaling Pathway in Patients with Esophageal Squamous Cell Carcinoma

“…All of the clinicopathological features (sex, age, tumor size and grade, histopathological stage, etc.) of the patients are mentioned in our recent studies (Table 1) [22,20,23,21,24].…”