High expression of EGFR predicts poor survival in patients with resected T3 stage gastric adenocarcinoma and promotes cancer cell survival

Abstract

Epidermal growth factor receptor (EGFR) is an essential regulator and biomarker of several types of cancer. However, the association between its expression and prognosis in patients with resected T3 stage gastric adenocarcinoma (RT3-GA) remains to be determined. In total, 683 patients with resectable T3-GA who underwent surgery were retrospectively included in the present study, and their immunohistochemical data for EGFR expression were collected. The associations between the patients' clinicopathologic characteristics and EGFR immunohistochemistry data were analyzed by multiple statistical methods. Annexin V apoptosis and MTT cell viability assays were performed to explore the effect of EGFR on AGS gastric adenocarcinoma cell survival. EGFR expression levels were categorized into two groups: low (406 cases) and high (277 cases). High EGFR was demonstrated to be significantly associated with distant metastasis (P=0.043) and severely decreased median overall survival time (MOST) and recurrence-free survival time (MRFST). MOST and MRFST in the low EGFR group were 39 and 37 months, respectively; whereas in the high EGFR group these values were only 18 and 13 months (P=3.10×10−9 and P=6.74×10−8, respectively). Multivariate analysis confirmed that high EGFR expression levels were associated with poor survival, which was associated with significantly increased recurrence risk and ~2-fold elevation in mortality risk [hazard ratio (HR), 1.73; 95% confidence interval (CI), 1.43–2.10; P=2.37×10−8 and HR, 1.80; 95% CI, 1.50–2.17; P=3.80×10−10]. Inhibiting EGFR with AG1478 suppressed its effect on promoting AGS cell survival. These results suggest that high EGFR expression indicates poor survival in patients with RT3-GA, which may be correlated with EGFR promoting GA cell survival.

MICAL‐L2 potentiates Cdc42‐dependent EGFR stability and promotes gastric cancer cell migration

“…Epidermal growth factor receptor (EGFR), a member of the ErbB family, is considered to be overexpressed in gastric cancer and play role in the development of tumourigenesis . Recent evidence shows that MICAL‐L1 mediates EGFR endocytosis, overexpression of MICAL‐L1 may lead to the accumulation of EGFR in the late endosomal compartment .…”

<p>Long noncoding RNA THAP9-AS1 is induced by <em>Helicobacter pylori</em> and promotes cell growth and migration of gastric cancer</p>

“…16,[20][21][22] Many products of protein-coding genes, such as CEA, HER2 and EGFR, have been investigated widely and function as diagnostic markers and therapeutic targets in the clinic. [23][24][25] Up to now, the early diagnosis and treatment of GC have been a global problem, and thus, we need a better understanding of the expression pattern of lncRNAs in GC cells. In view of the important cause of GC, we explored the expression patterns of lncRNAs in H. pylori-infected GC cells.…”

Identification of the Prognosis-Related lncRNAs and Genes in Gastric Cancer

“…Specifically, CTD-2218G20.2 was predicted to interact with 86 proteins (Pearson correlation coefficient, PCC > 0.3), some of which, including PSG4, PSG5, and PSG7, could also interact with cancer-related proteins, including KISS1, TIMP2, MMP11, IGFBP1, EGFR, and CDKN1C ( Figure 4A). Notably, KISS1, TIMP2, MMP11, IGFBP1, and EGFR have been reported to be involved in the metastasis of gastric cancer (Guan-Zhen et al, 2007;Kou et al, 2013;Wang et al, 2017;Wang et al, 2018;Sato et al, 2019). These results suggested that CTD-2218G20.2 might participate in the cancer progression via these cancer-related proteins.…”