scholarly journals Correlation between TXNRD1/HO-1 Expression and the Histological Response to Neoadjuvant Chemoradiation Therapy in patients with Esophageal Squamous Cell Carcinoma

2020 ◽  
Author(s):  
Ryujiro Akaishi ◽  
Fumiyoshi Fujishima ◽  
Hirotaka Ishida ◽  
Junichi Tsunokake ◽  
Takuro Yamauchi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
Carcinoma Cells ◽  
Histological Response ◽  
Biopsy Specimens ◽  
Before And After

Abstract BackgroundNrf2 signaling plays a pivotal role in antioxidant response, and its expression has been reported to increase in various human malignancies, including esophageal squamous cell carcinoma (ESCC). This also leads to resistance against chemotherapy and radiotherapy in patients. Thioredoxin reductase 1 (TXNRD1) and heme oxygenase-1 (HO-1) are proteins involved in this pathway that play key roles in antioxidant responses. However, the correlation between the expression of these two proteins and the therapeutic response to neoadjuvant chemoradiation therapy (NACRT), and the changes before and after chemoradiation therapy in patients with ESCC, remain unknown. MethodsThe proteins involved in the Nrf2 signaling pathway were immunolocalized in carcinoma cells in patients with ESCC undergoing NACRT with 5-fluorouracil and cisplatin followed by esophagectomy. The 8-OHdG levels were used to determine ROS levels in individual carcinoma cells. Fifty-two pre-operative endoscopic biopsy and fifty post-operative resected specimens were available for this study. Among these, 39 specimens were available for comparison of the results before and after NACRT. The changes in immunoreactivity before and after NACRT (Δ) were assessed. ResultsSignificant histological resistance to NACRT was observed in patients with high levels of Nrf2, TXNRD1, and HO-1 expression. Among pre-therapeutic biopsy specimens, the tumor reduction effect was significantly attenuated in those with high levels of Nrf2, TXNRD1, and HO-1 expression. TXNRD1Δ and HO-1Δ were both significantly higher, while 8-OHdGΔ was significantly lower in the ineffective (poor response) groups. In resected specimens, the overall survival was significantly lower in groups with high Nrf2, TXNRD1, HO-1, and HO-1Δ values. Disease-free survival was significantly lower in the groups with high expression of Nrf2, TXNRD1, HO-1, and Ki-67 and large values of HO-1Δ, and Ki-67Δ. ConclusionsThe results of this study indicate that high Nrf2, TXNRD1, and HO-1 expression in pre-therapeutic biopsy specimens could predict the histological response to NACRT, and their status in surgically resected specimens could predict clinical outcomes in patients with ESCC.

scholarly journals Correlation between TXNRD1/HO-1 expression and response to neoadjuvant chemoradiation therapy in patients with esophageal squamous cell carcinoma

Esophagus ◽  
2022 ◽  
Author(s):  
Ryujiro Akaishi ◽  
Fumiyoshi Fujishima ◽  
Hirotaka Ishida ◽  
Junichi Tsunokake ◽  
Takuro Yamauchi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
Nrf2 Pathway ◽  
Neoadjuvant Chemoradiation Therapy ◽  
Biopsy Specimens

Abstract Background Thioredoxin reductase 1 (TXNRD1) and heme oxygenase-1 (HO-1) are both involved in the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and play key roles in antioxidant responses. In patients with esophageal squamous cell carcinoma (ESCC), the correlation between the expression of these two proteins and the therapeutic response to neoadjuvant chemoradiation therapy (NACRT), as well as the difference in their expression after chemoradiotherapy, remains unknown. Methods Proteins involved in the Nrf2 pathway were immunolocalized in carcinoma cells in ESCC patients on NACRT with 5-fluorouracil and cisplatin, followed by esophagectomy. The 8-hydroxydeoxyguanosine (8-OHdG) levels were used to quantify reactive oxygen species. The changes in immunoreactivity before and after NACRT (Δ) were assessed. Results Tumor reduction following NACRT was significantly attenuated in pre-therapeutic biopsy specimens associated with high HO-1 status. TXNRD1Δ, HO-1Δ, and 8-OHdGΔ were significantly different in the ineffective and effective groups. The overall survival was significantly lower in high Nrf2 and TXNRD1 groups. In addition, high TXNRD1 expression was an independent prognostic factor in the multivariate analysis of overall survival. Conclusions The study findings indicate that HO-1 status in pre-therapeutic biopsy specimens could predict response to NACRT, and TXNRD1 status could predict overall survival of ESCC patients.

scholarly journals GR, Sgk1, and NDRG1 in esophageal squamous cell carcinoma: their correlation with therapeutic outcome of neoadjuvant chemotherapy

2020 ◽  
Author(s):  
Shunsuke Ueki ◽  
Fumiyoshi Fujishima ◽  
Takuro Konno ◽  
Hirotaka Ishida ◽  
Hiroshi Okamoto ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Neoadjuvant Chemotherapy ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cellular Response ◽  
High Status ◽  
Biopsy Specimens ◽  
Before And After ◽  
The Status

Abstract Background Esophageal squamous cell carcinoma (ESCC) is a highly malignant neoplasm. Glucocorticoid(GC)-Glucocorticoid receptor (GR) pathway plays pivotal roles in cellular response to various stresses of tumor cells including chemotherapy. However, the status of GC-GR pathway in ESCC, including its correlation with chemotherapeutic responses has remained largely unknown. Method GR, serum-and glucocorticoid-regulated kinase 1(Sgk1), and N-myc down regulation gene 1(NDRG1) were immunolocalized in 98 ESCC patients who had undergone esophagectomy following neoadjuvant chemotherapy(NAC) with 2 courses of 5-Fluorouracil(5-FU) + Cisplatin (CDDP). We also examined biopsy specimens before NAC in 42 cases and compared the results between those before and after NAC. Results Overall survival (OS) of the patients treated with surgery following NAC was significantly shorter in the group with high GR than that with low GR ( P = 0.0473). Both OS and disease-free survival (DFS) were significantly shorter in both Sgk1- and NDRG1-high groups than low groups (OS: Sgk1, P = 0.0055; NDRG1, P = 0.0021; DFS: Sgk1, P = 0.0240; NDRG1, P = 0.0086). When evaluating the findings in biopsy specimens before NAC, DFS was significantly shorter in the high Sgk1 group ( P = 0.0095), and both OS and DFS was shorter in high NDRG1 group (OS, P = 0.0233; DFS, P = 0.0006) than respective low groups. Among high NDRG1 group of biopsy specimens before NAC, the tumor reduction rate by NAC was significantly attenuated ( P = 0.021). Conclusions High status of GR, Sgk1, and NDRG1 in ESCC after NAC was significantly associated with over all worse prognosis and there were no significant changes in the status of those above before and after NAC. Therefore , increased activity of GC-GR pathway with enhanced induction of Sgk1 and NDRG1 in carcinoma cells plays pivotal roles in tumor progression and development of chemoresistance in ESCC patients undergoing NAC.

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