Combined Detection of HER2, Ki67, and GSTP1 Genes on the Diagnosis and Prognosis of Breast Cancer

Abstract

Objective: Breast cancer (BC) is a common malignant tumor in females. The combined assay of multiple molecular markers benefits the diagnosis and prognostic prediction. Human epidermal growth factor receptor 2 (HER2) facilitates the proliferation and differentiation of cancer cells through ligand binding. Ki67 is a tumor proliferation-related gene, whereas GSTP1 is a DNA repair-related gene. This study thus investigated the significance of HER2 and Ki67/GSTP1 gene combined assay in the diagnosis and prognosis of BC. Materials and Methods: A total of 86 breast tumor tissues and adjacent tissues were collected. Gene expression and protein levels of HER2 and Ki67 were quantified by real-time polymerase chain reaction (PCR) and Western blot, respectively. Methylation frequency of GSTP1 was analyzed by methylation-specific PCR. The correlation between HER2 and Ki67/GSTP1 and clinical/pathological features of BC was analyzed. Results: Gene and protein expression levels of HER2 and Ki67 in tumor tissues were increased (p < 0.05 compared with adjacent tissues). Methylation frequency of GSTP1 gene was 37.2%, which was significantly higher in breast tumor tissues than in adjacent tissues (12.79%, p < 0.05). HER2 expression was positively correlated with TNM stage, tumor size, and lymph node metastasis, and negatively correlated with tissue grade and estrogen receptor (ER)/progesterone receptor (PR) expression (p < 0.05). GSTP1 methylation was positively correlated with TNM stage and tumor size, and negatively correlated with ER/PR expression (p < 0.05). Conclusions: HER2, Ki67, and GSTP1 methylation were correlated with clinical and pathological features of BC. The combined assay benefits the early diagnosis and prognostic prediction of cancer.

Associations of Estrogen Receptor, Progesterone Receptor, Human Epidemic Growth Factor Receptor-2 and Ki-67 with Ultrasound Signs and Prognosis of Breast Cancer Patients

“… 7 Another study has indicated that Ki-67 expression has a positive correlation with TNM stage and LNM, and a negative correlation with tissue grade and ER/PR expression. 7 …”

“…Consistent with our findings, HER2 expression has been revealed to positively correlates with tumor size, clinical TNM stage and LNM, while negatively correlates with ER/PR expression and tissue grade, implying that HER2 expression could be considered as a marker for breast cancer. 7 Another study has indicated that Ki-67 expression has a positive correlation with TNM stage and LNM, and a negative correlation with tissue grade and ER/PR expression. 7 Furthermore, we wanted to elucidate the relationships between ER, PR, HER-2 and Ki-67 expression and prognosis in breast cancer tissues.…”

“…Nowadays, the molecular diagnostic technique has drawn some research interests due to its benefit in the diagnostic and prognostic assessment of breast cancer. 7 Breast cancer is traditionally assorted in the light of the presence of the steroid hormones, the receptors (estrogen receptor (ER), progesterone receptor (PR), human epidemic growth factor receptor-2 (HER2), as well as proliferation index Ki-67. 5 Currently, the immunohistochemistry-based molecular classification is suggested to have a close relationship with breast cancer prognosis, which is considered as a standard regimen for selecting the most useful approaches in breast cancer patient.…”

Promoter hypermethylation of CD133/PROM1 is an independent poor prognosis factor for head and neck squamous cell carcinoma

“…Recent evidence has shown that the combination of several epigenetic biomarkers can improve the diagnostic accuracy for cancers. [ 53 , 54 ] It would be logical that a panel of epigenetic biomarkers, including PROM1, represents a potential diagnostic test for HNSCC. Future rigorous studies using larger sample sizes will be essential to validate this approach.…”

Genetic and epigenetic modifications of HPDL and SOX17 associated with breast cancer prognosis: a study based on The Cancer Genome Atlas

“…Methylation of HER2, Ki67, and GSTP1 are associated with BRCA TNM staging and tumor size and can be combined for early diagnosis and prognosis [19]. FECR1 circular RNA expression is coordinated by regulation of DNA methylation and demethylation.…”