Identification of EGFR expression status association with metastatic lymph node density (ND) by expression microarray analysis of advanced gastric cancer

Abstract

Metastatic lymph node density (ND) has been reproducibly proven to be a prognostic factor in gastric cancer. The molecular mechanisms that underlie this aggressiveness are underexplored. Here, we aimed to identify molecules associated with this unique phenotype. Tumor specimens from patients with stage III gastric cancer with high or low ND (n = 4 for both) were compared at the mRNA level using Affymetrix microarray (harboring 54,675 genes). The expression data were prioritized, and genes that correlated with ND were selected. Ultimately, the EGFR was validated as such a candidate molecule in patients with primary advanced gastric cancer who underwent standard treatment (n = 167). Expression data of the microarray were prioritized based on gene expression ratio and frequency of gene expression. The first priority genes to be selected were genes that are known to be amplified in cancer, which included NKX2.1, CHST9, CTNND2, SLC25A27, FGFR2, EGFR, and PTGER1. Of these genes, the EGFR gene was of particular interest. EGFR expression in primary gastric cancer was examined using immunohistochemistry (IHC). The Student's t-test elucidated a significant difference in EGFR expression between IHC 2+/3+ and IHC 1+ according to ND (P = 0.0035). The Chi-square test also indicated a significant difference between high and low levels of EGFR immunohistochemical staining (IHC2+/3+ and IHC1+, respectively) and ND status (P = 0.0023). According to the least squares method, as ND increased, the risk that EGFR staining levels changed from IHC 1+ to IHC 2+ also increased. In this study, we determined that high EGFR expression may underlie the aggressive mechanism of advanced gastric cancer with high ND.

Immunohistochemical analysis of RTKs expression identified HER3 as a prognostic indicator of gastric cancer

“…In the present study, we analyzed prognosis using a cut‐off line between EGFR 1+ and 2+/3+ staining. This cut‐off line was used because staining of EGFR associated with massive lymph node metastasis was one of the strongest prognostic factors of gastric cancer that differed between 1+ and 2+/3+ . Even if we raised the cut‐off line to EGFR 1+/2+ expression, and compared EGFR 1+/2+ with 3+, the EGFR positive cases showed significantly poorer prognosis as compared to the EGFR negative cases ( P = 0.042) (data not shown).…”

CHST9 rs1436904 genetic variant contributes to prognosis of triple-negative breast cancer

“…It plays an important role in hematologic malignancies because CHST9 copy number variants (CNV) are associated with acute myelogenous leukemia (AML) 36 . Additionally, CHST9 CNV and amplification are also found in the brain of schizophrenia patients and gastric cancer patients with metastatic lymph node 37 , 38 . Nevertheless, the role of CHST9 as well as its genetic variations in breast cancer, especially TNBC, has not been determined.…”

The Role of the Lymph Node Ratio in Advanced Gastric Cancer After Neoadjuvant Chemotherapy

“…Improved understanding of GC biology will successively favor tailored surgery. Further research could possibly introduce LNR as a new biomarker [39], since it is closely associated with epidermal growth factor receptor (EGFR) expression [40].…”